Urology

A Solitary Seminoma Renal Metastasis Presenting as an Incidental Renal Mass

David A. Hadley, George H. Cannon, Jay T. Bishoff — 2009-08-05

A 34-year-old man with an extensive medical history received a CT scan for chronic leg and back pain. Imaging revealed a single, enhancing 8-cm mass in the upper pole of the right kidney. Laparoscopic radical nephrectomy was performed and pathologic finding revealed seminoma. Scrotal ultrasound and subsequent right orchiectomy also revealed seminoma. We discuss the occurrence of renal metastasis in seminoma.

Magnetic Resonance Imaging Characterization of a Mucinous Tubular and Spindle Cell Carcinoma of the Kidney Detected Incidentally During an Ectopic Pregnancy

Aidan P. Noon, David J. Smith, Philip McAndrew — 2009-12-04

Mucinous tubular and spindle cell carcinoma is an extremely rare variant of renal cell carcinoma, with only 47 cases reported previously. To our knowledge, this is the first time that contrast-enhanced magnetic resonance imaging reconstructive appearances and characteristics of this tumor have been published. This tumor presented incidentally in a 35-year-old woman with an ectopic pregnancy.

Testicular Metastasis of Prostatic Cancer

Chemsedine Smaali, Francoise Gobet, Fabrice Dugardin, Christian Pfister — 2009-11-13

Secondary testicular tumors are rare, we report a case of a solitary testicular metastasis of prostate cancer in 58-year-old man treated using hormonal therapy associated with radiotherapy. Ultrasound is the imaging modality of choice, but metastasis might be difficult to differentiate from primary tumors. The diagnosis confirmed by histologic examination includes routine microscopic and immunohistochemical findings, and therefore systemic treatment was required.

Preoperative Diagnosis of Malignant Mesothelioma of the Tunica Vaginalis Using Doppler Ultrasound

Piyush Aggarwal, Abhinav Sidana, Sadaf Mustafa, Ronald Rodriguez — 2009-12-07

Malignant mesothelioma (MM) of the tunica vaginalis is a rare aggressive tumor with a high predilection for metastatic spread. Because there is no preoperative diagnostic modality available, it has high recurrence and mortality rates, which emphasizes the importance of early preoperative diagnosis for proper and adequate treatment. We describe a case of MM of the tunica vaginalis in a 73-year-old man who presented with hydrocele and was preoperatively diagnosed with MM using Doppler in addition to scrotal ultrasound. He underwent early radical orchiectomy through an inguinal approach, resulting in improved survival.

Auto Amputation of Penis Due to Advanced Penile Carcinoma

Shanmugasundaram Rajaian, Ganesh Gopalakrishnan, Nitin S. Kekre — 2009-12-17

A middle-aged man presented with progressively enlarging ulcer on the tip of penis over a year's duration and sloughing of whole penis subsequently. Examination revealed complete loss of penis and purulent discharge at its base. Biopsy of the base of the penis confirmed penile carcinoma. Imaging studies revealed extensive metastatic lesions. Palliative care was given, but he succumbed later. In this era of advanced medical care, symptoms of penile cancer are still being ignored and have lead to autoamputation of penis.

Nonseminomatous Germ Cell Tumor of the Testes Metastatic to the Corpus Cavernosum of the Penis

Tom Feng, Jithin Yohannan, Mohamad E. Allaf — 2009-11-20

Metastases to the penis are rare, with less than 200 cases reported. Within the genitourinary tract, advanced prostate cancer is the most common culprit. These cases typically represent widely disseminated disease and are associated with a poor prognosis. We present images of a case of a testicular nonseminomatous mixed germ cell tumor, which metastasized to the corpus cavernosum of the penis 8 months after a negative bilateral retroperitoneal lymph node dissection. The patient received chemotherapy and experienced a complete response.

Quantification of Carbonic Anhydrase IX Expression in Serum and Tissue of Renal Cell Carcinoma Patients Using Enzyme-linked Immunosorbent Assay: Prognostic and Diagnostic Potentials

Grace X. Zhou, Joanna Ireland, Patricia Rayman, James Finke, Ming Zhou — 2009-12-07

Objectives: To validate enzyme-linked immunosorbent assay (ELISA) as an accurate and objective method to measure carbonic anhydrase IX (CAIX) expression in RCC tissue specimens and to also investigate the diagnostic and prognostic utility of serum CAIX levels. Recent studies found protein levels of CAIX, quantified using immunohistochemistry, correlated with clinical outcomes and therapeutic response to immunotherapy in advanced stage clear cell renal cell carcinoma (CCRCC).Materials and Methods: A CAIX ELISA kit was used to measure the CAIX levels in the serum and tissue of 21 CCRCCs and 19 non-CCRCCs. CAIX immunohistochemical stains were performed on the corresponding formalin fixed, paraffin embedded tumor tissues.Results: Tissue CAIX levels measured by ELISA highly correlated with the CAIX levels detected by immunohistochemistry (Pearson correlation coefficient = .802, P <.001). The CCRCC tumor tissue had significantly higher CAIX levels than non-CCRCC tissue (77 023 vs 938 pg/mL, P <.001) detected by ELISA. Serum CAIX levels in CCRCC patients were significantly higher than in non-CCRCC patients (126.1 vs 2.1 pg/mL, P = .013). The serum CAIX levels detected by ELISA correlated with the tumor size in CCRCC patients (Pearson correlation coefficient = .498, P = .036).Conclusions: ELISA provides a quantitative and objective method to measure CAIX levels in renal tumors. The tissue CAIX levels measured with ELISA highly correlate with the results obtained with the standard immunohistochemistry. Serum CAIX levels are significantly higher in CCRCC than in non-CCRCC and may aid the differential diagnosis of RCC. Serum CAIX levels also correlate with the tumor size in CCRCC patients.

Prediction of Clear Cell Renal Cell Carcinoma by Integrity of Cell-free DNA in Serum

2009-12-04

Objectives: To hypothesize that serum cell-free DNA integrity may be clinically useful for prediction of clear cell renal cell carcinoma (cRCC). The integrity of cell-free DNA released from cancer cells was different from that released from apoptotic cells.Methods: We collected peripheral blood samples from 78 patients before surgery; among these patients, 22 with tumor, both pre- and postoperation, and 42 controls without tumor. After the column extraction of DNA, we performed conventional polymerase chain reaction using different sizes of primers (size of products: 109, 193, 397, and 456 bp) of the housekeeping gene, glyceraldehyde-3-phosphate dehydrogenase for measurement of serum cf-DNA integrity.Results: Age and gender were not associated with cf-DNA integrity in controls (P = .136 and P = .345). Among the cRCC patients, we observed no significant association between cf-DNA integrity and gender, age, tumor grade (P = .510, P = .618 and P = .052), except tumor stage and size (P = .001 and P = .001). All specimens contained 109 bp products. The 193 bp product was detected in 75 of 78 cRCCs and 37 of 42 controls (P = .091), 21 of 22 patients preoperation and 19 of 22 postoperation (P = .294). The 397 bp product was detected in 71 of 78 cRCCs and 0 of 42 of controls (P = .001), 18 of 22 patients preoperation- and 7 of 22 postoperation (P = .003). The 456 bp product was detected in 69 of 78 of cRCCs and 0 of 42 of controls (P = .001), 18 of 22 preoperation and 3 of 22 postoperation (P = .002).Conclusions: Serum cf-DNA integrity may be a potential tool for the detection of clear cRCC.

Coded Tumor Size May Be Unreliable for Small Metastatic Renal Cancers in the Surveillance, Epidemiology, and End Results Dataset

Mike M. Nguyen, Inderbir S. Gill — 2009-11-13

Objectives: To report a weakness in the April 2006 release of the Surveillance, Epidemiology, and End Results (SEER) dataset, in which the primary tumor size of small (<1.8 cm) metastatic renal cancers was often incorrectly coded into the dataset from the measurement as listed in the patient's chart.Methods: In the SEER dataset, 167 patients with tumor size ≤2.5 cm had metastatic disease at presentation in 1998-2003. Each patient's chart was individually re-examined by SEER registries to determine the correct primary tumor size. This confirmed data were compared with the coded tumor size in the SEER dataset.Results: Of the 167 re-examined cases, 2 had incorrect histology and 6 could not be verified. Of the remaining 159 cases, 87 (55%) were correctly coded for primary tumor size while 72 (45%) were incorrect. The error rate decreased with increasing size; for tumors ≤1 cm, >1-2 cm, and >2-2.5 cm, error rates were 88%, 53%, and 6.8%, respectively (P <.001). A breakpoint in error rate occurred between tumor sizes <1.8 cm (78%) and ≥1.8 cm (10%) (P <.001). Most errors (72%) were miscoded by a factor of 10. Analysis of the latest April 2009 release suggests that most corrections have been incorporated into the public access dataset.Conclusions: Coded primary tumor sizes in the April 2006 release SEER dataset for metastatic renal tumors <1.8 cm from 1998 to 2003 were often inaccurate. Verification of tumor size in this subset was essential to insure data accuracy and quality of research. Researchers should recognize potential limitations of population-based cancer registries.

Editorial Comment

Gabriel P. Haas — 2010-02-01

This is a very thought-provoking manuscript, with important information for the readership. The Surveillance, Epidemiology, and End Results (SEER) database is the gold standard for our epidemiologic research. The statistics and trends reported there are widely quoted in research articles and text books, and form the bases of our eduction.

Nephron-sparing Surgery Is Equally Effective to Radical Nephrectomy for T1BN0M0 Renal Cell Carcinoma: A Population-based Assessment

2009-12-04

Objectives: To test the effect of nephron-sparing surgery (NSS) vs radical nephrectomy (RN) on cancer-specific mortality (CSM) in patients with T1bN0M0 renal cell carcinoma (RCC) in a population-based cohort. To date, only few series from tertiary care centers supported the use of NSS for T1bN0M0 (range 4-7 cm) RCC.Methods: The Surveillance, Epidemiology, and End Results database allowed us to identify 275 NSS (5.3%) and 4866 RN (94.7%) patients treated for T1bN0M0 RCC between 1988 and 2004. Analyses matched for age, year of surgery, tumor size, and Fuhrman grade addressed the effect of nephrectomy type (NSS vs RN) on CSM.Results: Five years after surgery, the surviving proportions of NSS and RN patients matched for age, tumor size, and year of surgery were respectively 91.4 and 95.3% and 90.1 and 93.8% in the cohort, where additional matching for Fuhrman grade was performed. Neither of the matched analyses resulted in statistically significant CSM difference (P = .1 and .4) between NSS and RN. Similarly, competing-risks regression analyses based on both matching schemes also failed to reveal statistically significant CSM differences (P = .3 and .3).Conclusions: Our study represents the largest and the only population-based analysis of cancer control efficacy of NSS vs RN in T1bN0M0 RCC. It indicates that NSS does provide equivalent cancer control relative to RN. In consequence, based on cancer control equivalence, NSS should be given equal consideration to RN in patients with T1bN0M0 lesions.

Editorial Comment

Paul Russo — 2010-02-01

In recent years, several important factors have been clarified that favor partial nephrectomy whenever possible for T1a (<4 cm) renal tumors. Approximately 20% of resected small renal masses are benign tumors (ie, renal oncocytoma, fat-poor angiomyolipoma), 25% are indolent tumors with limited metastatic potential (papillary renal cancer type 1, chromophobe carcinoma), and 54% are the more potentially aggressive conventional clear cell carcinoma. Oncological outcomes are equivalent irrespective of whether partial or radical nephrectomy is performed. Emerging evidence suggests that radical nephrectomy can induce or worsen pre-existing chronic kidney disease and lead to more cardiovascular events and worse overall survival. Single-institution studies have reported similar oncological efficacy for partial nephrectomy for T1b (4-7 cm) tumors and similar benefits of renal preservation. Patients particularly sensitive to the adverse effects of radical nephrectomy include the comorbidly ill patients with common medical illness that can affect the kidney (diabetes, hypertension, vascular disease) and in whom eGFR is reduced.

Reply

2010-02-01

X et al provide a very eloquent summary of the status of partial nephrectomy for T1bN0M0 lesions. Increasing evidence from centers of excellence, as well as from the current study that is based on a population registry, validates partial nephrectomy as an equally effective treatment modality compared with radical nephrectomy that may result in fewer adverse events. Longer follow-up, well in excess of the current study, will likely provide more solid data regarding long-term detriments of radical nephrectomy and will also probably further reinforce the benefits of partial nephrectomy.

Positive Surgical Margins With Renal Cell Carcinoma Have a Limited Influence on Long-term Oncological Outcomes of Nephron Sparing Surgery

2009-11-06

Objectives: To define the rate of positive surgical margins (PSMs) and analyze the outcome of patients with PSMs. The outcome and proper management of patients with positive PSMs during nephron sparing surgery (NSS) are questionable. In this study we define the clinical outcomes of PSMs at NSS and suggest management.Methods: Clinical records of 114 renal units who underwent open NSS for a renal mass between May 1995 and September 2005 were reviewed.Results: PSMs were suspected on frozen section in 17 of 114 renal units (15%). Tumors with suspected PSMs at frozen section were smaller (2.9 ± 1.6) in comparison to those with negative surgical margins (3.4 ± 1.8 cm) (P = .001). Nine of 17 (53%) cases underwent total nephrectomy (5 immediately, 4 delayed). In 4 (24%), immediate re-excision of the renal crater was performed. A total of 4 (24%) that were followed up clinically were with no evidence of disease. Therefore, in 13 of 17 (77%) cases, the presence of tumor cells at the remaining side of the kidney could be evaluated histologically. In 2 cases from the immediate response group, tumor cells were found in the side opposite to the resection. There was no residual tumor in any case subjected to delayed nephrectomy. At median follow-up of 71 months, 15 of 17 patients are alive and with no evidence of disease. Two patients died because of unrelated causes. The overall 5-year survival rate is 98.2% and there is no cancer-specific mortality.Conclusions: The true PSM rate is in the range of 1.75%-5.26%. No disease progression or deaths attributable to renal cell carcinoma were associated with PSMs. Total nephrectomy should be avoided as a response to PSMs.

Editorial Comment

Brian R. Lane, Steven C. Campbell — 2010-02-01

The authors present data regarding the limited effect of a positive parenchymal margin during partial nephrectomy on cancer-specific outcomes. Despite the finding of a positive margin in 17 patients (15%), only 2 of 13 sites assessed pathologically by either repeat resection or nephrectomy were found to contain residual cancer. None of these 17 patients experienced a recurrence or death due to renal cancer. These data agree with several other recent publications indicating that positive margins during partial nephrectomy have limited effect on cancer-specific outcomes. Although recent data indicate that enucleation (tumor resection without a margin) provides excellent oncologic outcomes, we believe that the goal of partial nephrectomy is complete tumor resection with a minimal rim of normal parenchyma. We agree with the authors' conclusion that in a majority of cases, a positive margin should not prompt immediate or delayed radical nephrectomy.

Editorial Comment

Steven J. Shichman — 2010-02-01

The management of the small renal mass (SRM < 4 cm) has undergone a paradigm shift in the past decade. Although surgical excision still remains the “gold standard,” we have seen a significant shift from open radical nephrectomy to laparoscopic radical nephrectomy and open partial nephrectomy, and more recently to laparoscopic and robotic-assisted partial nephrectomy. Additionally, ablative treatment options are gaining acceptance as primary treatment options.

Laparoscopic Partial Nephrectomy: A Single-center Evolving Experience

2009-12-04

Objectives: To review our laparoscopic partial nephrectomy (LPN) experience, examine the evolution of technique, and compare the outcomes between the early and recent experience. The indications and surgical technique of LPN continuously evolve.Methods: Data for 184 patients who underwent LPN for a tumor between October 2002 and August 2008 was retrieved from a prospective database. Surgical and functional outcomes for the entire cohort were analyzed and the first 50 (group 1) and most recent 50 (group 2) cases were compared.Results: The groups were similar in terms of baseline renal function, body mass index, and comorbidities. The mean tumor size and the proportion of central tumors in groups 1 and 2 were 2.4 vs 3 cm and 12% vs 52%, respectively (P 4 cm had more complications (P = .042). In group 2 the estimated blood loss and hospital stay decreased (243 vs 140 mL, P = .01, 1.4 vs 2.5 days, P <.001). Overall 78% of the tumors were malignant and the positive margin rate was 3%. With a median follow-up of 18 months, no local or distant tumor recurrences were observed.Conclusions: With growing experience and technical modifications, LPN is now performed for patients with larger and more central tumors. Longer follow-up is necessary to evaluate oncologic outcomes.

Editorial Comment

Rakesh V. Khanna, Robert J. Stein — 2010-02-01

The present study represents an analysis of the case selection and learning curve of a single surgeon with a large experience in laparoscopic partial nephrectomy (LPN). This group should certainly be applauded for their accomplishments, results, and judicious willingness to expand indications.

Critical Evaluation of Perioperative Complications in Laparoscopic Partial Nephrectomy

2009-12-07

Objectives: To analyze our experience with laparoscopic partial nephrectomy (LPN) to detail postoperative adverse events and identify factors that may contribute to adverse surgical outcomes. Complications from LPN result from a variety of factors, both technical and inherent.Methods: Single-center review of 144 consecutive LPN (4 surgeons) performed between November 2002 and January 2008 was conducted. Identified complications were graded using standard reporting criteria. Univariate and multivariate statistical analysis of variables and their association with complication event and blood loss was performed.Results: A total of 39 complications occurred in 29 (20%) cases. Of these, 20 (51%) were urologic and 19 (49%) were nonurologic. Individual adverse events by grade were as follows: grade I, 6 (15.4%); grade II, 19 (48.7%), grade III, 11 (28.2%), and grade IV, 3 (7.7%). No grade V complications occurred. The median tumor size and ischemia time were 2.7 cm and 35 minutes, respectively. Univariate analysis identified increased American Society of Anesthesiologists risk score (odds ratio 2.99, 95% confidence interval [CI] 1.28, 6.94) and ischemia time (odds ratio 1.31; 95% CI 1.00, 1.71) as associated with complication risk. On multivariate analysis, longer ischemia time was associated with increased estimated blood loss (95% CI 3, 57; P = .03). Hospital readmission and reintervention was required in 15 (10.4%) and 9 (6.2%) patients, respectively.Conclusions: Complications from LPN occur in a meaningful proportion of procedures although the majority does not require reintervention and half are not urologic. Increasing ischemia time and American Society of Anesthesiologists score are associated with risk for unfavorable surgical outcomes.

Predictors of Unilateral Renal Function After Open and Laparoscopic Partial Nephrectomy

2009-12-07

Objectives: To retrospectively evaluate clinical, tumor, and surgical factors that were potential predictors of postoperative unilateral renal function after laparoscopic and open partial nephrectomy.Methods: Sixty-five patients who had undergone partial nephrectomy and had postoperative renal scintigraphy performed were evaluated on the basis of multiple factors as potential predictors of postoperative renal function in the ipsilateral kidney. These factors include patient age, indication for nephron-sparing surgery, type of procedure (laparoscopic vs open), preoperative and postoperative glomerular filtration rate, tumor depth, radiographic and pathologic tumor size, warm ischemia time, and intraoperative visual assessment of functional renal parenchyma preserved. The correlation of each clinical factor to actual postoperative differential renal function, as determined by technetium-99m-mercaptoacetyltriglycine renal scintigraphy, was calculated.Results: In univariate regression analysis, the only factors found to be significantly correlated with postoperative unilateral renal function as assessed by renal scintigraphy were intraoperative visually estimated preserved parenchyma volume (P <.001), tumor size (radiologic, P = .017; pathologic, P = .041), and procedure type (P = .021). Tumor depth (P = .050) showed borderline significant relation to postoperative unilateral renal function. Multivariate analysis revealed no factors that were jointly prognostic for postoperative scintigraphic differential renal function.Conclusions: Intraoperative visually estimated functioning residual renal volume was the most accurate predictor of actual postoperative unilateral renal function. Tumor depth had intermediate prognostic value in estimating postoperative split renal function. During both laparoscopic and open partial nephrectomy, intraoperative visual estimation of preserved renal parenchyma volume should be routinely documented.

Synchronous Cryoablation of Multiple Renal Lesions: Short-term Follow-up of Patient Outcomes

Guarionex Joel DeCastro, Mantu Gupta, Ketan Badani, Greg Hruby, Jaime Landman — 2009-11-20

Objectives: To report on various perioperative and short-term clinical outcomes of 7 patients who underwent cryoablation of multiple renal lesions during the same operative setting. Cryotherapy is the most well studied minimally invasive ablative technique for the treatment of renal tumors.Methods: A retrospective analysis of our institutional renal cryotherapy database yielded a total of 7 patients who underwent synchronous cryoablation of > 1 renal lesion between August 2005 and May 2007.Results: Mean patient age was 63.9 years, and median follow-up was 23.3 months (range 7-28 months). Five patients had ablation of 2 renal lesions, 1 had 3 lesions, and 1 had 4 lesions. The mean greatest diameter of any single lesion was 2.0 cm (range 0.7-7.5 cm). Mean preoperative serum creatinine was 1.5 mg/dL (range 0.7-3.6 mg/dL), which increased to a mean of 1.7 mg/dL (range 0.7-3.6) at last follow-up. Mean estimated blood loss was 138 mL (range 38-300 mL). There were 2 complications—ureteral stenting because of postoperative renal colic, and blood transfusion for decreased hematocrit. Of the 17 lesions, 7 were found to be conventional renal cell carcinoma, 4 papillary, 2 myelolipoma, and 1 oncocytoma (unavailable for 3 lesions). Mean length of hospital stay was 2.3 days (range 1-6 days). At last follow-up, computed tomography scanning demonstrated no recurrences in any patient.Conclusions: Cryoablation of multiple renal lesions at one setting may be successfully performed with few complications, with minimal short-term loss of renal function as estimated by serum creatinine, and with short-term evidence of tumor destruction.

Tumor Size and Endophytic Growth Pattern Affect Recurrence Rates After Laparoscopic Renal Cryoablation

2009-11-25

Objective: To analyze factors that may contribute to local relapse after laparoscopic cryoablation (LCA) of renal tumors. LCA has gained popularity in the treatment of small renal tumors, but local tumor control remains a concern.Methods: We analyzed 163 patients who underwent LCA between 2001 and 2008 either at Allegheny General Hospital or Duke University Medical Center, with at least 6 months of follow-up. Demographics, perioperative variables, tumor characteristics (size, pattern of growth, and biopsy results), and follow-up were recorded. Growth pattern was categorized as exophytic, mesophytic, or endophytic. Regression analyses were performed to evaluate risk factors for local relapse after LCA.Results: Median patient age was 66 (range, 33-90) years, with men comprising 60.1% of the cohort. Median tumor size was 2.4 cm (range, 0.5-5.0). Pathology was as follows: renal cell carcinoma in 118 (72.4%), other malignancies in 2 (1.2%), and no malignancy in 43 (26.4%) patients. A single lesion was treated in 95.1% patients and multiple tumors in 4.9%. Endophytic growth pattern was present in 22.8% patients. We observed 7 (4.3%) local recurrences over a median follow-up of 20 months (range, 6-79). Median time to recurrence was 15 months (range, 6-48). On proportional hazards regression, tumor size and endophytic growth pattern were significantly associated with local recurrence (P = .003 and .028; odds ratios [OR] = 4.1 and 11.4, respectively).Conclusions: LCA demonstrated good tumor control over a 5-year follow-up, with an acceptable recurrence rate. Larger tumors and those with endophytic growth pattern may be at increased risk of relapse after LCA.

Laparoscopic Cryoablation of Renal Masses: Which Lesions Fail?

Timothy R. Yoost, Harry S. Clarke, Stephen J. Savage — 2009-12-17

Objective: To identify potential predictive characteristics of lesions which failed in laparoscopic renal cryoablation (LRC). We analyzed 47 lesions that underwent this approach.Methods: We reviewed 45 consecutive patients who underwent LRC of a renal mass between 2003 and 2008 at a single institution. A total of 47 masses were identified; all were treated by 2 surgeons. We analyzed patient age, ASA, pre- and postoperative creatinine, tumor size, location, number of cryoprobes used, and histology of the lesions. We reviewed imaging to identify characteristics of those lesions which failed LRC management, defined as lesions that demonstrated persistent enhancement and/or did not decrease in size within 6 months of therapy.Results: A total of 47 lesions in 45 patients were identified. The median follow-up was 13 months. Mean lesion size was 2.7 cm (range, 1.2-5.4), with 25 anterior and 22 lateral or posterior lesions. Of the biopsy samples from 40 of 47 lesions, renal cell carcinoma was found in 23, oncocytoma was found in 7, and 10 were benign or inconclusive. Treatment failure was noted in 8 of 47 lesions (17%), 7 of which (87.5% of failed lesions) had broad-based contact with the renal sinus. Broad-based lesions which made contact with the renal sinus were successfully treated 53.3% of the time, whereas lesions which lacked contact with the renal sinus were treated successfully 96.9% of the time (P <.01).Conclusions: Broad-based central location of a renal mass may predict a significantly increased risk of failure of LRC and should be considered in patient counseling.

A Population-based Assessment of Perioperative Mortality After Nephroureterectomy for Upper-tract Urothelial Carcinoma

2009-12-07

Objectives: To examine the perioperative mortality rates at 90 days (90 dM) after nephroureterectomy (NU) and to devise a model capable of identifying individuals at an elevated 90 dM risk. NU represents the surgical standard of care for patients with invasive, nonmetastatic upper-tract urothelial carcinoma. However, this major abdominal surgery may be associated with a nonnegligible rate of perioperative mortality.Methods: We identified 6078 upper-tract urothelial carcinoma patients treated with NU from 17 registries of the Surveillance, Epidemiology, and End Results database, between 1988 and 2006. Stratified analyses quantified 90 dM rates according to age, gender, race, year of diagnosis, tumor location, surgery type, T stage, tumor grade, and lymph node status. Subsequently, multivariable logistic regression models identified predictors of 90 dM within the development cohort (n = 3039). The accuracy and calibration of the model were tested in an independent validation cohort (n = 3039).Results: The overall 90 dM rate was 4.4%. Continuously coded age and T and N stages achieved an independent predictor status in multivariable logistic regression models and represented key variables for prediction of individual 90 dM risk after NU, with 73.4% accuracy. Excellent correlation between predicted and observed 90 dM rates after NU was recorded.Conclusions: In this large-scale population-based analysis of perioperative mortality after NU, age and T and N stages emerged as the most informative predictor of 90 dM. We recommend the use of this tool in individual decision-making and in informed consent considerations.

Gender-related Differences in Patients With Stage I to III Upper Tract Urothelial Carcinoma: Results From the Surveillance, Epidemiology, and End Results Database

2009-12-04

Objectives: To examine the effect of gender in upper tract urothelial carcinoma (UTUC) stage at nephroureterectomy (NU), as well as on cancer-specific mortality (CSM) after NU in patients with American Joint Committee on Cancer stages I-III UTUC.Methods: Our analyses relied on 2903 (59.9%) males and 1947 (40.1%) females who underwent an NU for pT1-3N0/xM0 UTUC between 1988 and 2006, within 17 Surveillance, Epidemiology, and End Results registries. Univariable and multivariable logistic regression models examined the effect of gender on stage and grade distribution at NU. Subsequently, cumulative incidence plots explored the impact of gender on CSM rates, after accounting for other-cause mortality (OCM). Finally, competing-risks regression models tested the independent predictor status of gender in CSM analyses. Covariates consisted of pT stage, pN stage, tumor grade, primary tumor location, type and year of surgery, age, and race.Results: Relative to males, females had a higher proportion of pT3 UTUC (43.1% vs 39%; P = .02) and a higher proportion of grade III/IV UTUC (63.8% vs 59.8%; P = .04) at NU. The female gender represented an independent predictor of pT3 UTUC at NU (hazard ratio [HR]: 1.15; P = .03). After accounting for OCM, CSM rates in females were higher than those in males (HR: 1.18; P = .03). However, in multivariable competing-risks regression models, no statistically significant differences in survival were recorded between males and females (HR: 1.07; P = .4).Conclusions: Females are more likely to have more advanced pathologic T stage and higher tumor grade at NU than males. After accounting for OCM, stage, grade, and noncancer characteristics, gender no longer affects CSM.

Lymphovascular Invasion and pT Stage Are Prognostic Factors in Patients Treated with Radical Nephroureterectomy for Localized Upper Urinary Tract Transitional Cell Carcinoma

2009-12-17

Objectives: To investigate the prognostic significance of lymphovascular invasion (LVI) in patients with localized upper urinary tract transitional cell carcinoma (UUT-TCC) after radical nephroureterectomy.Methods: The clinical records of 271 patients with UUT-TCC who underwent radical nephroureterectomy between 1986 and 2006 were reviewed. Patients with pT4 stage, lymph node involvement, or distant metastasis were excluded. A total of 238 patients with pTa-3N0M0 were eligible. The prognostic significance of various clinicopathologic factors was analyzed using univariate and multivariate analysis. The mean age was 64.1 years (range, 25-91 years) and the median follow-up duration was 53.4 months (range, 3-240 months).Results: LVI was present in 31 patients (13%). LVI was related to higher pT stage, high tumor grade, sessile architecture, and squamous differentiation. On univariate analysis, tumor architecture, squamous differentiation, LVI, tumor grade, and pT stage influenced disease-specific survival. On multivariate analysis, LVI (hazards ratio [HR], 2.33; P = .014) and pT stage (HR, 2.07; P = .021) showed significantly different rates of disease-specific survival. Patients were classified according to pT stage and LVI. The high-risk group (pT3 and LVI+) showed significantly worse disease-specific survival than the low- (pT ≤ 2 and LVI−) or intermediate-risk groups (pT3 and LVI−, pT ≤ 2 and LVI+) (P <.001 and P = .032, respectively).Conclusions: LVI and pT stage are significant prognostic factors for recurrence-free and cancer-specific survivals in patients with localized UUT-TCC. LVI and pT stage would be helpful for selecting patients who are appropriate for postoperative adjuvant chemotherapy.

Editorial Comment

Bobby Shayegan — 2010-02-01

In this study, the authors present their long-term single-center experience with radical nephroureterectomy for upper tract urothelial carcinoma (UTUC). Similar to the vast majority of studies previously reported, the current study is retrospective in nature, albeit with a reasonably large cohort of patients. However, owing to the relatively low incidence of UTUC, prospective cohort studies are difficult to perform and high quality retrospective analyses form the basis of our current knowledge in this area.

Editorial Comment

Robert E. Weiss — 2010-02-01

During the metastatic cascade, cancer cells lose adhesion, increase their motility, and develop means to invade blood vessels and lymphatics for migration. Lymphovascular invasion is clearly one of the most critical steps in the cancer cell's ability to metastasize. The importance of lymphovascular invasion has been shown to be an important prognostic factor in other urologic malignancies including bladder, prostate, and testis. The authors present their experience evaluating the prognostic significance of lymphovascular invasion and upper tract transitional cell carcinoma. Of the 271 patients, lymphovascular invasion was present in 31 (13%). They showed that the combination of lymphovascular invasion and tumor stage were significant prognostic factors in predicting recurrence-free and cancer-specific survival. The authors' findings support the data from others who have demonstrated that lymphovascular invasion predicts clinical outcome in patients with upper tract urothelial cancer.

Bladder Cancer Detection, Treatment and Outcomes: Opportunities and Challenges

David M. Latini, Seth P. Lerner, Sally W. Wade, David W. Lee, Diane Z. Quale — 2009-12-07

Bladder cancer (BlCa) is the fifth most common cancer in the United States and one of the ten deadliest. It ranks fifth among all cancers in total costs, consuming almost $3 billion annually, and has an extensive effect on quality of life for survivors and their families. Despite this human and economic toll, BlCa ranks comparatively low on the national agenda. Our understanding of this disease has grown exponentially over the last decade, paving the way for better prevention, detection, treatment, monitoring, and quality of life. Increasing national attention to BlCa is likely to improve disease burden and patient quality of life.

Evidence-based Principles of Bladder Cancer and Diet

Jonathan L. Silberstein, J. Kellogg Parsons — 2009-10-12

Bladder cancer presents a substantial challenge to public health. Dietary factors influence the risk of bladder cancer incidence and recurrence and may offer innovative therapies for prevention. Agents associated with decreased risk of bladder cancer include carrots, selenium, cruciferous vegetables, and fruits. Dietary components associated with increased bladder cancer risk include pork, barbecued meats, fat, soy, and excessive coffee consumption. Although definitive clinical trials have yet to be performed, promotion of healthy lifestyle interventions based on dietary factors—increased vegetable and fruit intakes, decreased meat and fat intakes—should be considered in the care of patients with bladder cancer.

Comparative Genomic Hybridization Analysis Reveals New Different Subgroups in Early-stage Bladder Tumors

2009-08-03

Objectives: To classify bladder tumors according to their genomic imbalances and evaluate their association with patient's outcome.Methods: Sixty-three superficially and minimally invasive bladder tumors were analyzed by conventional comparative genomic hybridization. Subtelomeric screening in 15 of these tumors was performed by multiplex ligation-dependent probe amplification.Results: Losses of 9q and 9p (32% and 25% of all cases, respectively) as well as gains of chromosomes Xq and Xp (28% and 25%, respectively) were the most frequent chromosome imbalances. Losses of 8p and gains in 1q and 8q were detected in >20% of cases. Tumors were classified into 3 groups according to their individualized pattern of gains and losses. The largest group was characterized by few chromosome imbalances, presenting 77% and 49% of the Ta and T1 tumors, respectively. Another group characterized by chromosomal gains, was composed of equal number of Ta and T1 tumors, with +1q and +17q gains being the most common imbalances. A minority group was characterized by chromosomal losses on 11q, 5q, and 6q. The multiplex ligation-dependent probe amplification study showed good correlation with comparative genomic hybridization results. With regard to the biological significance of this classification, a remarkable fact is that this minority group composed mainly of T1 tumors, showed a significant decrease in patient overall survival.Conclusions: Our data suggest that superficial carcinomas of the bladder can be subdivided into a larger number of subclasses than had previously been expected. Our results also demonstrate a decreased survival among patients whose tumors show more genomic losses than gains.

Editorial Comment

Violeta Menendez — 2010-02-01

Bladder tumors show widely differing histopathology and clinical behavior. This is reflected in the molecular genetic alterations they contain. Much information has accumulated on somatic genomic alterations in bladder tumors of all grades and stages. Heterogeneity and unpredictable behavior of this type of tumors make necessary the use of combinations of markers that may provide information predictive of prognosis or response to specific forms of therapy.

Reply

Rosa Miró — 2010-02-01

We are grateful for the positive editorial comment regarding the clinical potential of classifying bladder tumors according to the predominance of gains or losses. Understanding the genetic events leading to bladder cancer progression is important in decreasing the overall morbidity and mortality associated with the disease.

The Role of Actinin-4 in Bladder Cancer Invasion

2009-12-07

Objectives: To examine actinin-4 expression levels in bladder cancer, in particular its levels during cellular growth and invasion. Actinin-4 is an actin-binding protein that is associated with cell motility and cancer metastasis.Methods: Relative messenger ribonucleic acid (mRNA) and protein expression of actinin-4 in normal bladder and bladder cancer cell lines was determined by quantitative real-time polymerase chain reaction and Western blot analysis. Actinin-4 expression was also localized in bladder cancer cells and tissues using immunohistochemistry. The growth and invasion activity of bladder cancer cells was evaluated using cell growth and in vitro cell invasion assays, and compared with that of bladder cancer cells treated with actinin-4 small interfering ribonucleic acids.Results: Actinin-4 mRNA and protein levels were elevated in bladder cancer cells that are known to exhibit increased growth and invasion activity. Protein expression was predominantly observed in the cytoplasm of the invasive bladder cancer cells and tissues. Treatment of bladder cancer cell lines with actinin-4 small interfering ribonucleic acids suppressed the invasive potential of the cells, but did not alter their growth.Conclusions: The current study demonstrates that actinin-4 mRNA and protein levels are elevated in bladder cancer cells lines that exhibit increased growth and invasion activity. In addition, actinin-4 knockdown inhibited invasion of bladder cancer cells, but did not alter their growth. In conclusion, we hypothesize that the accumulation of actinin-4 in the cell cytoplasm is related to an increased susceptibility of tumor invasion and metastasis.

“Complete Transurethral Resection of Bladder Tumor”: Are the Guidelines Being Followed?

2009-12-07

Objectives: To determine how often complete eradication of all visible tumors during transurethral resection of bladder tumor (TURBT) is accomplished in a referral setting. The American Urological Association guidelines recommend complete eradication whenever possible.Methods: We retrospectively reviewed the records of patients who underwent a second TURBT within 4 weeks of being referred to us. Relevant data such as residual tumor location, number, stage, and grade were collected and analyzed. Patients with muscle invasive tumor or known incomplete resection were excluded.Results: Forty-seven patients met the inclusion criteria. Mean age was 75 years. In the initial TURBT, 35 (75%) had a high grade tumor and 12 (25%) had low grade tumors. Twenty-four (52%) were Ta and 23 (48%) were T1 tumors. Of the 47 patients who satisfied the criteria, 33 (70%) had an initial incomplete resection. Of these, 10 (30%) had macroscopic residual tumor at the resection site. Twenty-three (70%) had at least 1 unresected tumor away from the previous resection site. There were 39 unresected or partially resected tumors. Thirteen (33%) tumors were located in the anterior wall, 12 (31%) in the posterior wall and trigone, 10 (26%) in the lateral wall, 3 (7.5%) in the dome, and 1 (2.5%) in the prostatic urethra.Conclusions: Although TURBT is a commonly performed operation, in this selected series, the incidence of unresected and gross residual tumor after initial TURBT is high. This indicates a need to emphasize the guidelines for a complete resection and to emphasize the use of a proper technique in this commonly performed urological procedure.

Editorial Comment

Ryan K. Berglund — 2010-02-01

The authors of this study look at their experience in restaging transurethral resection of bladder tumor (TURBT) in a referral setting, with the hypothesis that the presence of disease at restaging TURBT is an indicator of an incomplete initial resection. They find a high rate of residual disease (70%), with 30% of those patients having residual disease at the original site of resection and 70% having disease at another site. This leads them to conclude that “urologists may not be uniformly performing a complete TURBT. Efforts should be directed to improve the completeness of resection.” While they do acknowledge the limitations of a small, retrospective, single-institution study in reaching that conclusion, their point is well taken. As they cite in the article, a good resection should include muscle in the specimen, and a restaging procedure should provide no new information.

Reply

2010-02-01

We appreciate Dr. Berglund's comments. I think it is important to distinguish our series from the rest that have examined the incidence of residual tumor, and when present, the staging discrepancy between the original transurethral resection (TUR) and the routine second TUR (reTUR). In some of those analyses, the population consisted of patients who had TUR of a bladder tumor either by a different urologist or by the same urologist, with the primary goal of determining whether there is residual tumor in the bladder and the grade and stage of any such tumors. In our series of 47 patients, all underwent the first TUR by a referring urologist, and the second TUR or reTUR was performed by the senior author within 4 weeks of the first procedure. The fact that 70% of this selected group of patients had an incomplete resection (10/33 had macroscopic tumor) was surprising and highlights the importance of performing at least an endoscopy before proceeding with a bladder preserving treatment, eg, intravesical therapy, for patients referred with Ta tumors and a formal reTUR for all T1 tumors.

Editorial Comment

Harry W. Herr — 2010-02-01

The aim of transurethral resection (TUR) is to resect all nonmuscle-invasive bladder tumors, but surgery as currently practiced fails in a significant proportion of patient's resection. Incomplete TURs are partly due to the number, size, location, and extent of bladder neoplasm, and in part due to the lack of experience, skill, and diligence of the surgeon. Confirming these observations, the authors provide guidelines to improve the quality of TUR of bladder tumors. Their recommendations are too general and lacking in detail, however, to be useful in individual cases. They state, “Every effort should be made to resect all tumors.” How?

Reply

Mark S. Soloway — 2010-02-01

The intent of our article was not to describe in detail the technique of accomplishing a complete endoscopic resection of all bladder tumors, as I have coauthored chapters addressing some of the excellent points indicated by Dr Herr in his editorial comments. Rather this article aimed to stress that, for a variety of reasons, a high percentage of patients with Ta and T1 bladder tumors do not undergo a complete resection. One would have to assume, possibly incorrectly, that a urologist performing a TUR of bladder tumors would try to remove all tumors. The fact that macroscopic tumor remains in the bladder within 4 weeks before resection indicates that this procedure is not easily performed. This might be because tumors are located in a region of the bladder that is difficult to visualize, the bladder is thin and the surgeon is concerned about perforation, or the equipment is substandard and does not allow a successful procedure. Attention to detail is required. Among the requirements for success in the outcome of patients with Ta−T1 bladder tumors is accurate staging as well as removal of all evident tumor before proceeding with intravesical therapy, or a bladder preservation strategy for T2 tumors. In either case, there is agreement that the results are far better when all tumors have been eradicated before embarking on prophylaxis or treatment. As Dr Herr correctly emphasizes, the guideline for a reTUR for high grade T1 and for some high grade Ta tumors is to help ensure accuracy in staging. A 3 month delay in the proper management of high grade bladder cancer can be catastrophic.

Bladder Preservation in Octogenarians With Invasive Bladder Cancer

2009-12-17

Objectives: To analyze mortality and morbidity of octogenarians with newly diagnosed invasive transitional cell cancer (TCC) of the bladder who were managed without cystectomy.Methods: Retrospective chart review of all patients with newly diagnosed invasive TCC (≥pT1) in the period of 1997-2007, who were 80 years or older at diagnosis.Results: A total of 71 patients (86 + 4 years, mean + standard deviation [SD], pT1: n = 29; >pT2: n = 42) entered this analysis. In this geriatric population, treatment regimens were highly individualized. After transurethral resection, 61% of pT1-patients received bacillus Calmette-Guerin and 62% of those with >pT2-tumors external beam radiation. Mean overall survival (OS) of the entire cohort (n = 71) was 22 + 26 months for pT1-patients 34 + 33 versus 14 + 15 months for those with ≥pT2-tumors (P = .001). Mean cancer-specific survival was 58 months for pT1-patients and 11 months for ≥pT2-patients (P pT2-tumors.Conclusions: OS in TCC is dependent on tumor stage, age, mobility, and comorbidities, and a risk-stratified management is necessary. Patients with pT1G3 tumor and low ASA score have satisfying OS with bladder preservation, but in patients with ≥pT2 and ASA 3-4 the prognosis is very bad. It remains questionable whether patients with tumor stages ≥pT2 and ASA 1-2 despite high age would benefit from radical cystectomy.

Adenocarcinoma Versus Urothelial Carcinoma of the Urinary Bladder: Comparison Between Pathologic Stage at Radical Cystectomy and Cancer-specific Mortality

2009-12-17

Objectives: To compare stage at radical cystectomy (RC) and cancer-specific mortality (CSM) after RC between non-urachal adenocarcinoma (ADK) and urothelial carcinoma (UC) of the urinary bladder.Methods: Within 17 Surveillance, Epidemiology and End Results registries, we identified ADK and UC patients who underwent a RC between 1988 and 2006. We examined differences in stage and grade at RC between ADK and UC patients. Kaplan–Meier plots depicted CSM after RC. Cox regression analyses examined CSM rates, adjusted for T and N stages, tumor grade, age, gender, race, and year of surgery. Thereafter, we relied on statistically significant variables from the multivariate Cox regression model to match ADK and UC patients. Finally, we plotted Kaplan–Meier survival curves of the matched ADK and UC patients.Results: Of 306 ADK and 11 697 UC patients, 188 (61.4%) and 5538 (47.3%), respectively, showed extravesical disease (pT3-4; P <.001) and 26.5% vs 21.7% had lymph node metastases at RC (P = .04), respectively. After adjustment for all covariates, including stage and grade, ADK was not associated with worse prognosis than UC (hazard ratio, 1.05; P = .6). Similarly, after matching, no difference in CSM was recorded between the 2 histologic subtypes (hazard ratio, 1.07; P = .5).Conclusions: ADK patients undergo RC at more advanced disease stages. However, stage- and grade-adjusted CSM is the same between ADK and UC patients. Efforts should be aimed at providing definitive treatment at earlier stages, especially in patients with ADK histologic subtype.

Aggregate Lymph Node Metastasis Diameter and Survival After Radical Cystectomy for Invasive Bladder Cancer

2009-10-12

Objectives: The current tumor-node-metastasis (TNM)–staging system for urothelial carcinoma of the bladder (UCB) is based on the number and size of the largest positive lymph node (LN). The aggregate LN metastasis diameter (ALNMD) may better reflect the burden of metastatic disease and improve the ability to predict recurrence-free (RFS) and overall survival (OS).Methods: Clinical characteristics and follow-up information of 134 patients with LN-positive UCB treated by radical cystectomy was modeled using Cox proportional hazards regression analysis to predict OS. Pathologic specimens were retrospectively reviewed by a single genitourinary pathologist unaware of treatment outcome to determine the greatest dimension of metastasis in all affected LN. The median follow-up of survivors was 23 months.Results: The median OS was 17 months; median LN density, 17%; and median number of LN removed, 14. ALNMD was a significant predictor of RFS and OS after adjusting for pathologic T stage, lymphovascular invasion, LN density, comorbidity, and extranodal extension (adjusted HR 1.1; P = .02), even when restricting the analysis to patients in whom 10 or more LN have been removed. The predictive accuracy of a model for OS that contained ALNMD was superior to the one without this parameter and the TNM-staging system (c-index 0.71 vs 0.67 vs 0.62).Conclusions: ALNMD is a significant predictor of RFS and OS after adjusting for standard prognostic parameters among patients with LN-positive UCB and may be a useful parameter to include in future predictive nomograms and TNM-staging systems.

Initial Experience of Diffusion-weighted Magnetic Resonance Imaging to Assess Therapeutic Response to Induction Chemoradiotherapy Against Muscle-invasive Bladder Cancer

2009-11-16

Objectives: To investigate the feasibility of diffusion-weighted magnetic resonance imaging (DWI) in predicting therapeutic response to low-dose chemoradiotherapy (LCRT) against muscle-invasive bladder cancer (MIBC). Accurate assessment of response to induction therapy is an essential part of bladder-sparing therapeutic protocols against MIBC. However, conventional imaging studies are not useful in evaluating therapeutic response because of their inability to distinguish residual cancer from changes secondary to the treatment.Methods: Twenty patients with clinical T2-4aN0M0 bladder urothelial carcinoma (T2/T3/T4a: n = 10/8/2) who underwent induction LCRT comprising external beam radiotherapy to the bladder (40 Gy) concomitant with 2 cycles of cisplatin administration (20 mg/d for 5 days) followed by partial (n = 13) or radical cystectomy (n = 7) were prospectively enrolled. The patients underwent magnetic resonance imaging examinations with T2-weighted imaging (T2W), dynamic contrast-enhanced T1-weighted imaging (DCE), and DWI after LCRT. A finding of each protocol was compared with a pathologic finding of cystectomy specimen.Results: Pathologic examination of cystectomy specimens revealed pathologic complete response in 13 (65%) of the 20 patients. The sensitivity/specificity/accuracy of T2W, DCE, and DWI in predicting pathologic response was 43/45/44%, 57/18/33%, and 57/92/80%, respectively. Despite comparable sensitivity, DWI was significantly superior in specificity and accuracy to T2W (P = .03 and .02, respectively) and DCE (P = .002 for both).Conclusions: This is the first study to show the feasibility of DWI over T2W and DCE for assessing therapeutic response to induction chemoradiotherapy against MIBC. The high specificity of DWI indicates that DWI is useful to accurately predict pathologic complete response, allowing more optimal patient selection in bladder-sparing protocols.

Editorial Comment

Harry W. Herr — 2010-02-01

Proper selection and accurate evaluation of response to induction chemoradiation therapy is a prerequisite to successful bladder-sparing strategies. In this pilot study, the authors propose that diffusion-weighted magnetic resonance imaging (DWI) assessed the therapeutic response to initial therapy better than conventional magnetic resonance imaging. To their credit, they correlated their imaging assessments with the pathologic findings after patients had undergone either radical or partial cystectomy. They studied 20 patients and 7 (35%) had residual cancer. A 30% understaging rate after initial chemotherapy for muscle-invasive bladder cancer is what we expect from bladder-preservation series. The challenge lies in identifying those patients clinically. Of the 20 patients, 4 had macroscopic residual lesions detected by DWI and 3 had microscopic tumor that was missed. These patients had postchemoradiation cystoscopy; however, not all had a biopsy, and none was described as having an aggressive transurethral resection (TUR) of the primary tumor site. A post-treatment restaging TUR likely would have revealed residual microscopic disease within the bladder wall, which is unlikely to be detected by any current imaging modality, including DWI.

Reply

Fumitaka Koga, Soichiro Yoshida, Kazunori Kihara — 2010-02-01

We greatly appreciate the editorial comment on our study and the opportunity to discuss how to accurately evaluate response to induction therapy in bladder-sparing strategies against muscle-invasive bladder cancer (MIBC).

Impact of Comorbidity on Survival of Invasive Bladder Cancer Patients, 1996-2007: A Danish Population-based Cohort Study

2009-11-16

Objectives: To examine (i) the prevalence of comorbidity among invasive bladder cancer (IBC) patients, and (ii) the effect of comorbidity on IBC survival and mortality in Northern Denmark. Comorbidity has shown to be associated with treatment selection and survival in patients who undergo radical cystectomy for IBC.Methods: Patients with a diagnosis of IBC from Danish hospitals between 1996 and 2007 within a population of 1.6 million were identified through the Danish National Patient Registry. From hospital diagnosis data, we computed Charlson Comorbidity Index scores (0, 1-2, 3+) for IBC patients and computed absolute survival and relative mortality estimates according to comorbidity level.Results: We identified 3997 patients with IBC among whom 1715 (43%) had comorbidities. The prevalence of comorbidity tended to increase during the study period with those having scores 3+ increasing from 8%-12%. Three- and 5-year mortality rates were higher for patients with comorbidity, with mortality rates more than 2-fold higher among those with scores of 3+ and 1.5-fold higher among those with scores of 1-2 compared with no comorbidity. Generally, the same pattern was seen for 1-year relative survival rates.Conclusions: Comorbidity was seen among 43% of IBC patients and severe comorbidity was a predictor of poorer survival.

Editorial Comment

Angela B. Smith, Raj S. Pruthi — 2010-02-01

Radical cystectomy remains the gold standard for invasive bladder cancer. Although this treatment provides the best local disease control and long-term disease-free survival, morbidity and mortality are important considerations for the physician when choosing appropriate therapeutic modalities for patients. Contemporary reports reveal estimated mortality rates from radical cystectomy in the range of 0.7%-5.6%. Isbarn et al provide a recent population-based assessment of perioperative mortality after cystectomy for bladder cancer using data extracted from 4 SEER registries between 1984 and 2004, and found that perioperative mortality at 30, 60, and 90 days were 1.1%, 2.4%, and 3.9%, respectively. Their analysis evaluated the effect of age, stage, and grade, but a significant limitation was the exclusion of comorbidity, which may arguably play a large role in perioperative mortality after radical cystectomy.

The Unintended Burden of Increased Prostate Cancer Detection Associated With Prostate Cancer Screening and Diagnosis

Peter C. Albertsen — 2009-11-23

The increasing incidence of prostate cancer is associated with the intensity of screening for prostate-specific antigen. Although some men may benefit from the early detection of prostate cancer through screening, all men diagnosed with prostate cancer experience an effect on their mental and physical well-being and that of their families. In light of the recent publication of the United States Preventive Services Task Force recommendations concerning prostate-specific antigen testing, this article reviews the quality-of-life implications of prostate cancer screening and diagnosis, and explores risk reduction in screened men as a potential strategy to manage these issues.

Editorial Comment

Paul H. Lange — 2010-02-01

Dr. Albertson has been a leader in delineating the natural history of prostate cancer and warning us about overdetection and treatment. This review article enhances this reputation; it is complete and clearly written. He reminds us again that we are picking up too much prostate cancer, we are treating too many of them at significant morbidities, and although the death rate is declining in many western countries and the best controlled randomized trial (ie, the European ESRPC) suggests survival benefit, there is an alarmingly high rate of overdiagnosis. One estimate suggests that almost 1500 cases need to be screened for 50 cancers to be detected to cure 1 man. It is no wonder that the U.S. Preventive Task Force (References and in the article) and maybe the American Cancer Society are going on record against widespread early detection and all concerned organizations recommend careful education of the patient before testing. Yet we all know that a true orientation can be time prohibitive and much of the time these men say, “what would you do and what do you recommend I do?”

Reply

Peter C. Albertsen — 2010-02-01

I appreciate Dr. Lange's kind words and agree with his conclusions. We cannot embrace a “no screening” policy. The ERSPC study has shown that screening can reduce prostate cancer mortality within 8 years of diagnosis. Furthermore, this benefit may increase as we follow patients for a longer duration. There are major differences however, in the way PSA testing is practiced in the United States and that described in the ERSPC study.

Canary Prostate Active Surveillance Study: Design of a Multi-institutional Active Surveillance Cohort and Biorepository

2009-09-16

Active surveillance is a management plan for localized prostate cancer that offers selective delayed intervention on indication of disease progression, allowing patients to delay or avoid treatment and associated side-effects. Outcomes from centers that promote active surveillance are favorable, with high rates of disease-specific survival. However, there remains a need for prognostic variables or biomarkers that distinguish with high specificity the aggressive cancers that progress on surveillance from the indolent cancers. The Canary Prostate Active Surveillance Study is a multicenter study and a biorepository that will discover and confirm biomarkers of aggressive disease as defined by histologic, prostate-specific antigen, or clinical criteria.

Treatment Outcomes of Radical Prostatectomy in Potential Candidates for 3 Published Active Surveillance Protocols

C. Shad Thaxton, Stacy Loeb, Kimberly A. Roehl, Donghui Kan, William J. Catalona — 2009-12-07

Objectives: To examine the treatment outcomes of men who would have been eligible for active surveillance (AS) but underwent immediate radical retropubic prostatectomy (RRP). AS protocols are designed to spare the potential morbidity of treatment to patients with low-risk prostate cancer (PCa).Methods: From a prospective RRP database, we evaluated the tumor features and treatment outcomes for men who would have met 1 of 3 published AS criteria: (1) clinically localized disease, Gleason ≤7, and no significant comorbidities (Patel et al, J Urol. 2004;171:1520-1524) (2) T1b-T2b N0M0 disease, Gleason ≤7, and prostate-specific antigen ≤15 ng/mL (Choo R et al. J Urol. 2002;167:1664-1669), or (3) T1c PCa (Mohler JL et al. World J Urol. 1997;15:364-368.).Results: 3959, 3536, and 2330 RRP patients, respectively, would have met these AS criteria. At surgery, 3%-4% had a Gleason score of 8-10, 16%-19% had positive surgical margins, 15%-18% had extracapsular tumor extension, 3%-5% had seminal vesicle invasion, and 0.4%-1% had lymph node metastasis. The 5-year progression-free survival rate ranged from 84%-89%. Metastasis occurred in 0.1%-1.2%, and 0.1%-0.9% died of PCa. On multivariate analysis, Gleason score >6 was the strongest predictor of biochemical progression.Conclusions: A substantial proportion of men who might have been considered potential AS candidates had aggressive tumor features at RRP and/or progression. Biopsy Gleason score >6 was the strongest predictor of adverse outcomes, highlighting the importance of limiting AS to patients with Gleason ≤6. Overall, the accurate identification of patients with truly indolent PCa at the time of diagnosis remains challenging.

Editorial Comment

Marc Birkhahn, Richard J. Cote — 2010-02-01

Prostate cancer is the most common malignancy and the second leading cause of cancer death in men. As a result of widespread screening efforts instituted in the late 1980s, especially serum screening for prostate-specific antigen (PSA) and greater application of digital rectal examination, prostate cancer is increasingly detected at a localized stage. This has resulted in a dramatic increase in the numbers of prostate cancers diagnosed each year, which is clear from the comparison of the number in this decade with the decades before the 1990s. Because of the favorable outcomes for patients with early stage prostate cancer, there have been increasing questions regarding the efficacy and need for aggressive screening for this disease. Of particular note are questions regarding the need for definitive treatment for much of the prostate cancer diagnosed by current screening methods. Recently, 2 large PSA screening trials indicating that large numbers of patients are treated to save a single patient from death due to prostate cancer have attracted a great deal of attention in the scientific community and the lay press. These studies concluded that most patients with prostate cancer undergo unnecessary treatment, which can itself lead to substantial reduction in quality of life.

Reply

William J. Catalona — 2010-02-01

Physicians and patients continue to struggle with the often-quoted conundrum of Willett F. Whitmore Jr: Is cure of prostate cancer possible when necessary and necessary when possible?

Outpatient Prostatectomy: Too Much Too Soon or Just What the Patient Ordered

2009-12-07

Objectives: To evaluate the feasibility of performing a robot-assisted radical prostatectomy (RARP) as an outpatient procedure while maintaining patient satisfaction and safety. Herein we report our experience, selection criteria, and discharge criteria for outpatient RARP.Methods: We performed a prospective study with 11 patients undergoing extraperitoneal RARP. These patients were counseled before the procedure that they would go home the same evening of the procedure. The patients were then surveyed by a third party shortly after they returned home, using the Patient Judgement System-24, a previously validated instrument for patient satisfaction. Sociodemographic data, comorbidities, and outcomes were collected for analysis.Results: All patients were successfully discharged the same day of surgery. Mean patient age was 62.2 years with a mean body mass index of 26 kg/m2. Mean operative time was 117.6 minutes, console time was 76.7 minutes, and estimated blood loss was 168.2 mL. Mean indwelling catheter time was 7.5 days. No complications occurred in this series of patients. Satisfaction was unanimously high in all patients surveyed, with most scores over 90% on the Patient Judgement System-24. No patient reported any ill effects from the shortened stay or felt rushed to leave the hospital.Conclusions: The early experience with extraperitoneal RARP as a same day surgery is promising. Preoperative patient counseling and selection is paramount. Patient satisfaction is not adversely affected by the shortened stay. Surgeon experience, assessment of intraoperative findings, and adequate postoperative assessment are essential.

Editorial Comment

Alireza Moinzadeh — 2010-02-01

As the health care reform bill is currently being debated, the publication of this manuscript appears timely. However, aspiring to perform major urologic procedures as an outpatient is not novel. Several authors have successfully demonstrated the feasibility of outpatient procedures, including laparoscopic pyeloplasty, radical perineal prostatectomy, nephrectomy, and laparoscopic adrenalectomy. Despite the passage of nearly 10 years since the first of these publications, immediate discharge after major urologic procedures is not common practice.

Reply

Aaron D. Martin, Erik P. Castle — 2010-02-01

We appreciate the reviewer's thoughtful response and agree that the concept of same day discharge can be challenging for many to accept. Although the above points are valid concerns, they should not be considered a roadblock to performing major urologic procedures in an outpatient setting. Robotic surgery has pushed open surgeons to challenge dogmatic postoperative pathways leading to shorter hospital stays and catheter times for both minimally invasive and open radical prostatectomy. We all remember the open prostatectomy patients who stayed 3 or more days in the hospital and had 2-3 weeks catheter times. Should robotic surgeons settle with our current outcomes or push the envelope even further so long as patient care is not compromised?

Editorial Comment

Mark S. Litwin — 2010-02-01

President Kennedy established one of his most enduring legacies when he announced in 1962, “We choose to go to the moon in this decade and do the other things, not because they are easy, but because they are hard.” He went on to contend that this goal would “serve to organize and measure the best of our energies and skills.” He could not have anticipated that his clarion call to push ourselves might be applied, almost 5 decades later, to minimizing length of stay in hospital after radical prostatectomy. In both trajectories, our results have been stellar.

Reply

Aaron D. Martin, Erik P. Castle — 2010-02-01

Although the advancements in treatment for prostate cancer may never be as glamorous as space travel or climbing Mount Everest, it has arguably affected more lives. Hospital stays for radical prostatectomy have not necessarily shortened because of superior outcomes as much as because of improved postoperative pathways. Our study shows properly selected and counseled patients can be sent home the same day of surgery without compromising on their oncologic outcomes or well-being. Radical prostatectomy has truly become minimally invasive, offering patients effective cancer control with little interruption in their daily lives. Many patients will attest that they prefer recovery in the comfort of their own home to the busy hospital atmosphere.

Has the Advent of Minimally Invasive Surgery Altered the Risk Profile of Patients Undergoing Prostatectomy?

2009-11-25

Objectives: To determine whether the decreased short-term morbidity associated with minimally invasive surgery (MIS) has resulted in an alteration in the disease-specific risk profile of prostatectomy patients. MIS in many fields has resulted in an expansion in the pool of patients willing to undergo surgery.Methods: The Columbia Urologic Oncology Database was queried, and 1751 patients undergoing radical prostatectomy between 2000 and 2007 were identified. The cohort was divided into 2 groups: patients who received surgery before or after the initiation of robotic-assisted laparoscopic radical prostatectomy (RALRP) at our institution (from 2003 onward). Age at surgery, Kattan Nomogram (KN) score, prostate-specific antigen (PSA), Gleason score sum, and tumor stage were compared using unpaired t tests with Welch correction and Mann–Whitney tests.Results: A total of 663 patients underwent prostatectomy from 2000 to 2002 (“pre-MIS era”), and 1088 patients had surgery in 2003 or later (“MIS era”), of which 519 and 569 underwent RALRP and open prostatectomy, respectively. There was no significant difference between the 2 eras regarding age, Kattan Nomogram score, or tumor stage. However, there was a significant difference in preoperative PSA (P = .01) and Gleason sum (P = .0002). In a comparison of the pre-MIS era with RALRP patients, only PSA differed significantly (P = .0002).Conclusions: The advent of MIS for prostate cancer did not significantly alter the characteristics of patients undergoing prostatectomy at our institution. Although advancements in surgical techniques may improve clinical outcomes, this study does not suggest a consequential effect on the risk stratification of patients choosing surgery for prostate cancer.

Analysis of Continence Rates Following Robot-assisted Radical Prostatectomy: Strict Leak-free and Pad-free Continence

2009-10-26

Objectives: To propose a strict and specific definition of continence (leak-free and pad-free [LFPF]) and apply it to robot-assisted radical prostatectomy (RARP) outcomes on the basis of University of California-Los Angeles-Prostate Cancer Index (UCLA-PCI), as postprostatectomy incontinence is not well defined.Methods: A single-institution RARP database was reviewed concerning continence variables prospectively recorded by the UCLA-PCI. Specific responses to urinary function and continence items were reviewed at baseline and 1, 3, 6, 12, and 24 months after surgery.Results: From February 2003 to September 2007, a total of 1005 of 1500 RARP patients had data available for review. At baseline, only 73% of these patients were LFPF. This decreased to 4%, 9%, 17%, 24%, and 28% at 1, 3, 6, 12, and 24 months after surgery, respectively. Applying less strict definitions, at 24 months, 68% of patients reported no pad use and 90% of patients reported no pad use or the use of a security pad. When stratified by baseline LFPF status, patients not LFPF at baseline had higher baseline international prostate symptom score scores, lower urinary function scores, lower urinary bother scores, and larger prostate weights. Patients LFPF at baseline disproportionately regained LFPF continence starting 6 months after surgery compared with those not LFPF at baseline: 20% vs 9% (P = .005), 27% vs 15% (P = .0009), and 33% vs 15% (P = .0146) at 6, 12, and 24 months, respectively.Conclusions: A strict definition of urinary continence results in more conservative postoperative outcomes. Preoperative LFPF status can be predictive of postoperative LFPF continence. However, only one-third of patients LFPF at baseline returned to LFPF at 24 months.

Editorial Comment

Craig V. Comiter — 2010-02-01

Along with the stage and grade of prostate cancer, the risk of urinary incontinence is often one of the most heavily weighted factors in driving treatment decisions. However, the prevalence of postprostatectomy “incontinence” varies depending on the definition of incontinence and the method of evaluation. Although the International Continence Society has clearly defined stress incontinence, this definition depends on whether one is referring to the patient's history, physical examination, or urodynamic evaluation.

Reply

W. Stuart Reynolds, Kevin C. Zorn — 2010-02-01

We certainly would agree with the editorial comment that the definition of leak-free and pad-free continence is not standard and not explicitly validated as an independent metric. However, its strength is its simplicity and directness, which can make interpretation easier for the patient and clinician. How this definition is related to “bother” is much more problematic, as the effect of bother on quality of life outcomes is difficult to characterize and assess. Particularly in the common patient who is not completely continent and requires only 1 pad per day, the range of “bothersomeness” is wide and the actual degree of incontinence is difficult to characterize. For example, one patient may use a thin liner primarily for security while another uses a full pad per day for moderate leakage. Both of whom would be included in the “1 pad per day” group. Most importantly, within our own medical community, we need to better standardize the definition of postprostatectomy incontinence for formal outcomes reporting and to better address patients' expectations for recovery after treatment.

Editorial Comment

Mark S. Litwin — 2010-02-01

In his treatise on what defines the acme of success, both in the business world and throughout the realm of human endeavors, author Jim Collins contends that good is the enemy of great. That is, many of us settle for good because we are not inspired enough to accomplish great. A critical element in the path to greatness, he posits, emanates from a laser sharp and passionate focus on the central goal of the enterprise. Keep your eye on the ball. But the ball should be clearly visible to be seen.

Reply

W. Stuart Reynolds, Arieh L. Shalhav — 2010-02-01

The purpose of this study is to compare different definitions for continence and to demonstrate how it affects continence outcomes. The contribution of this knowledge is that it allows building realistic patient expectation during preoperative consultation. The poetic editorial regarding the number of cases performed in the United States and selection of active surveillance vs intervention is beyond the scope of this manuscript.

Freedom From a Detectable Ultrasensitive Prostate-specific Antigen at Two Years After Radical Prostatectomy Predicts a Favorable Clinical Outcome: Analysis of the SEARCH Database

2009-10-12

Objectives: To assess the utility of kinetics for ultrasensitive prostate-specific antigen (uPSA) assays to identify men who are at risk of developing high-risk recurrent prostate cancer [prostate-specific antigen doubling time (PSADT) < 9 months] after radical prostatectomy. Previous studies demonstrate that a PSADT < 9 months after radical prostatectomy is associated with prostate cancer-specific mortality. Conventionally, PSADT has been calculated after biochemical failure (PSA ≥ 0.2 ng/mL).Methods: A review of the Shared Equal Access Regional Cancer Hospital database from 1988-2008 was performed to identify men with biochemical failure after radical prostatectomy and ≥ 2 uPSA values before failure (PSA ≥ 0.2 ng/mL) as well as ≥ 2 values after failure to calculate PSADT. These patients were stratified into low-risk (PSADT ≥ 9 months) and high-risk (PSADT < 9 months) cohorts. The following uPSA kinetics were analyzed for their ability to predict low- and high-risk cohorts: time to first detectable uPSA, time from uPSA to biochemical failure, uPSA velocity, uPSADT, uPSA exponential rise, and uPSA fluctuations.Results: The analysis included 89 low- and 26 high-risk men. Time to first detectable uPSA was inversely associated with the high-risk cohort (OR 0.96, 95% CI 0.92-0.99, P = .02) and characterized by a high sensitivity and negative predictive value at a threshold of 2 years after surgery. Other measures of uPSA kinetics showed no association with PSADT.Conclusions: Time to first detectable uPSA identifies men with low-risk recurrence prostate cancer. Patients with an undetectable uPSA 2 years after surgery are unlikely to develop PSADT < 9 months after biochemical failure.

Editorial Comment

Kevin M. Slawin — 2010-02-01

The authors of this study demonstrate that time to a detectable uPSA of ≥ 0.01 ng/mL is a significant predictor of the clinical course following biochemical failure (BCR) after radical prostatectomy, with aggressive disease defined as a PSADT of < 9 months, conferring a 0.5-1 year lead time (ie, 2-2.5 years postprostatectomy) over the 3-year cut point using a standard PSA assay suggested by Freedland et al. However, they also caution that a detectable uPSA level arising earlier than 2 years from surgery cannot reliably predict the presence or subsequent clinical course of biochemical failure. Our experience with ultrasensitive PSA during this early period suggests that uPSA levels can predict the risk of future BCR, although we have not yet studied the correlation with high-risk disease or PCSM. In a presentation at the AUA in 2008, we reported our experience with 792 consecutive patients who underwent radical prostatectomy by a single surgeon (28% performed robotically) for clinically localized prostate cancer, who were followed up routinely using an ultrasensitive PSA assay (Immulite 2000 third Generation PSA, Siemens Medical) beginning at least 6 weeks after surgery. This cohort was relatively high risk, with 60% of patients having a Gleason score ≥ 7, 31.7% exhibiting ECE, 9.4% SM+, and 4.2% LN+. Cox proportional hazards modeling including standard postoperative parameters and stratification by the first postoperative ultrasensitive PSA level ≤ 0.01 was performed. The median follow-up was 25 months (IQR 11-43.8). A total of 615 (77.7%) patients achieved a ≥ 6- week postoperative uPSA of ≤ 0.01 ng/mL. Using a BCR threshold definition of 0.2 or more or any use of salvage radiation or hormonal therapy, the hazard ratio for recurrence when the first postoperative uPSA level ≤ 0.01 was 0.18 (95% CI, 0.1-0.34, P 1 PSA assay platform may have limited the predictive value of uPSA at earlier time points in the present published study, and suggest that a 0.03 ng/mL cut point for BCR may not apply universally. These studies in aggregate suggest that routine use of ultrasensitive PSA after prostatectomy would at the very least help physicians evaluate their surgical technique when the goal is complete removal of the prostate gland and increase the available data for future studies that would further define the promising role of uPSA in predicting the clinical course after radical prostatectomy.

Reply

Steven L. Chang, Joseph C. Presti — 2010-02-01

The reviewer makes a compelling argument that uPSA assays may in fact be useful for all patients after surgery rather than applied to patients who have developed a biochemical recurrence. The work by Slawin et al not only suggests that uPSA values represent a clinical tool to predict future BCR but also potentially identifies those patients who will continue to have a rising PSA beyond 0.2 ng/mL—men who nadir at a uPSA of 0.03 ng/mL or greater. Although this report is contradictory to an earlier study by Amling et al that suggests postoperative PSA values < 0.5 ng/mL may be inconsequential, the utility of uPSA assays to predict subsequent changes in postoperative PSA are supported by several recent studies.

Editorial Comment

Judd W. Moul — 2010-02-01

In the setting of defining PSA recurrence (PSAR) after radical prostatectomy (RP), on the surface, it would seem easy. The prostate is gone and the PSA should be gone. However, in the real world practice setting it is commonly confounded by definitions of recurrence, residual cancer cells vs benign prostate tissue, miscommunications or misunderstanding, and ultrasensitive PSA vs standard PSA measurements.

Reply

Steven L. Chang, Joseph C. Presti — 2010-02-01

Prostate-specific antigen (PSA) monitoring after radical prostatectomy is far from simple and straightforward in patients with a detectable PSA. Not only can this confusion cause undo stress for clinicians and patients, but also misinterpretation of PSA values may potentially result in a worse clinical outcome from overtreatment or undertreatment with secondary therapy. The objective of the present study was to clarify the interpretation of postoperative PSA in men with biochemical recurrence after radical prostatectomy.

Urinary Prostate Cancer 3 Test: Toward the Age of Reason?

2009-07-08

The prostate cancer 3 (PCA3) gene was discovered in 1999, on the basis of differential expression between cancer and noncancerous prostate tissue. Including the first study published in 2003, 11 clinical studies have evaluated its utility for the diagnosis of prostate cancer by measuring the number of PCA3 RNA copies in urine enriched with prostate cells. Although the sensitivity of the PCA3 test was less than that of serum prostate-specific antigen (PSA), its specificity appeared to be much better, particularly in patients with a previous negative biopsy. Recent studies also have suggested that this test could be used to predict cancer prognosis.

Editorial Comment

Leonard S. Marks — 2010-02-01

The most remarkable feature of this excellent review is that its material has evolved rapidly and without any naysayers! The initial publication on the PCA3 gene (DD3) appeared in 1999, and the test that is now commercially available was first reported in 2006. In only a few years, 11 clinical trials of PCA3 as a test for prostate cancer (CaP) have been reported all of which have been positive. Has a molecular “Age of Reason” arrived?

Serum Level of Clusterin and Its Density in Men with Prostate Cancer as Novel Biomarkers Reflecting Disease Extension

2009-10-26

Objectives: To assess whether the serum level of clusterin and its density could be used as novel biomarkers of prostate cancer.Methods: Sera were obtained from 380 patients with prostate cancer and 120 with benign prostatic hyperplasia. Serum clusterin level was measured by a sandwich enzyme immunoassay, and clusterin density, which was determined by dividing the serum clusterin level by the prostate volume, was also calculated. These findings were analyzed with respect to several clinicopathologic factors.Results: The mean serum level of clusterin in prostate cancer patients was significantly higher than that in the benign prostatic hyperplasia group. Both the serum clusterin level and clusterin density in prostate cancer patients were significantly associated with major prognostic factors other than biopsy Gleason score. Of the 380 prostate cancer patients, 162 underwent radical prostatectomy and pelvic lymphadenectomy, and 104 and 58 were diagnosed as having organ-confined and extraprostatic diseases, respectively. The clusterin density in patients with organ-confined disease was significantly higher than that in patients with extraprostatic disease; however, there was no significant difference in the serum clusterin level between these 2 groups. Furthermore, biochemical recurrence-free survival in patients with elevated clusterin density was significantly lower than that in patients with normal density.Conclusions: These findings suggest that serum clusterin level and its density could serve as a useful practical adjuncts to conventional parameters for estimating the extension of prostate cancer.

Tumor Volume, Tumor Percentage Involvement, or Prostate Volume: Which Is Predictive of Prostate-specific Antigen Recurrence?

2009-10-12

Objectives: To compare the effects of tumor volume (TV), tumor percentage involvement (TPI), and prostate volume (PV) on prostate-specific antigen (PSA) recurrence (PSAR) after radical prostatectomy (RP).Methods: A cohort of 3528 patients receiving RP between 1988 and 2008 was retrieved from the Duke Prostate Center. Patients were stratified by TV (< 3, 3-6, > 6 cm3), TPI (< 10%, 10%-20%, > 20%), and PV (< 35, 35-45, > 45 cm3) and their effects on PSAR evaluated using Kaplan-Meier analysis. Clinicopathologic variables included in univariate analysis were age at surgery, race, year of surgery, PSA, pathologic Gleason score, pathologic tumor stage, margin status, extracapsular extension, and seminal vesicle invasion. The effects of TV, TPI, and PV (as continuous and categorical variables) on PSAR were compared using Cox analysis.Results: TPI, TV, and PV were predictive of PSAR (P 20% and PV 10-35 cm3 were predictive of PSAR (HR = 1.45 and OR = 1.25, P <.05). TV was not predictive of PSAR in either analysis. Pathologic Gleason score ≥ 7, PSA, positive margins, seminal vesicle invasion, and tumor stage T3/T4 were found to be predictors of PSAR (P <.05).Conclusions: TV, TPI, and PV were predictive of PSAR in univariate analysis, but in multivariate analysis, only TPI and PV were predictive of PSAR. TPI and PV should be considered when evaluating, assessing, and counseling patients regarding PSAR risk.

The Importance of Serum Prostate-specific Antigen Testing Frequency in Assessing Biochemical and Clinical Failure After Prostate Cancer Treatment

2009-10-28

Objectives: To assess the relationship between prostate-specific antigen (PSA) testing frequency and biochemical failure (bF) and clinical failure (cF).Methods: The records of 5616 patients with low-, intermediate-, or high-risk prostate cancer treated (brachytherapy, external beam radiotherapy, or surgery) between 1996 and 2007 were reviewed. Factors influencing bF and cF were recorded including age, initial PSA, androgen deprivation, race, clinical stage, biopsy Gleason score, and the frequency of follow-up PSA testing. Univariate and multivariate analyses were performed to assess the effect of these factors on bF and cF. Sensitivity and specificity were calculated to determine the optimal frequency of PSA testing.Results: The median follow-up is 45 months. The median number of PSA tests per year before the occurrence of bF and cF is 1.9 for both endpoints. The multivariate analysis of factors significantly associated with bF and cF demonstrate that PSA frequency, initial PSA, clinical stage, and biopsy Gleason score are independently predictive of outcome. PSA testing achieves the best sensitivity and specificity when 2 PSA tests are drawn per year for both bF (sensitivity = 66.3%, specificity = 58.0%) and cF (sensitivity = 75.1%, specificity = 60.3%).Conclusions: The frequency of PSA testing is strongly associated with the detection of bF and cF. Because it is a variable that can be controlled, PSA testing frequency should be standardized to minimize spurious conclusions from studies with bF and cF endpoints. The sensitivity and specificity can be optimized by obtaining 2 PSA tests per year.

Focal Treatment or Observation of Prostate Cancer: Pretreatment Accuracy of Transrectal Ultrasound Biopsy and T2-weighted MRI

2009-07-30

Objectives: To test the hypothesis that men with prostate cancer (PCA) and preoperative disease features considered favorable for focal treatment would be accurately characterized with transrectal biopsy and prostate magnetic resonance imaging (MRI) by performing a retrospective analysis of a selected cohort of such patients treated with radical prostatectomy (RP).Methods: A total of 202 patients with PCA who had preoperative MRI and low-risk biopsy criteria (no Gleason grade 4/5, 1 involved core, <2 mm, PSA density ≤0.10, clinical stage ≤T2a) were included in the study. Indolent RP pathology was defined as no Gleason 4/5, organ confined, tumor volume <0.5 mL, and negative surgical margins. MRI ability to locate and determine the tumor extent was assessed.Results: After RP, 101 men (50%) had nonindolent cancer. Multifocal and bilateral tumors were present in 81% and 68% of patients, respectively. MRI indicated extensive disease in 16 (8%). MRI sensitivity to locate PCA ranged from 2% to 20%, and specificity from 91% to 95%. On univariate analysis, MRI evidence of extracapsular extension (P = .027) and extensive disease (P = .001) were associated with nonindolent cancer. On multivariate analysis, only the latter remained as significant predictor (P = .0018).Conclusions: Transrectal biopsy identified men with indolent tumors favorable for focal treatment in 50% of cases. MRI findings of extracapsular extension and extensive tumor involving more than half of the gland are associated with unfavorable features, and may be useful in excluding patients from focal treatment. According to these data, endorectal MRI is not sufficient to localize small tumors for focal treatment.

Impact of Disease Burden on Cryoablation Prostate-specific Antigen Outcomes

David A. Levy, Jianbo Li, Stephen Jones — 2009-12-07

Objectives: To identify prognostic factors for favorable biochemical outcome (prostate-specific antigen [PSA] <0.6 ng/mL) after primary whole gland prostate cryoablation.Methods: The charts from 122 cryoablation patients treated at Cleveland Clinic from 2004 through May 2009 were reviewed. Patient age, race, PSA at diagnosis, Gleason score, risk category, prostate gland volume, clinical T stage, number of cores positive, percent of core involved with disease, ratios of number of cores positive to total cores biopsied and number of cores positive to prostate gland volume, and initial PSA results were studied. An initial post-cryoablation PSA of <0.6 was used as the criterion for favorable outcome based on previously published data.Results: A total of 16.4% of patients had unfavorable postoperative PSA levels. On univariate analysis, number of cores positive (P = .031) and maximum percent core positive (P = .024) were prognostic of PSA outcome. On multivariate analysis, number of cores positive (P = .010), maximum percent core positive (P = .034), and ratio of number of positive cores to prostate gland volume (cm3) (P = .023) were prognostic for favorable PSA outcomes based on an initial PSA <.6 ng/mL.Conclusions: Favorable PSA outcomes after primary prostate cryoablation appear to be correlated with disease burden. The relative disease burden as defined by the number of and percent core positive, and the ratio of number of cores positive to prostate gland volume (cm3) are highly prognostic for initial post-cryoablation PSA <0.6 ng/mL, which is associated with favorable long-term biochemical disease-free survival regardless of risk stratification.

Correlation of Thermocouple Data With Voiding Function After Prostate Cryoablation

David A. Levy — 2009-10-26

Objectives: To identify possible correlations of thermocouple recorded data with altered postoperative voiding function after prostate cryosurgery.Methods: A retrospective analysis of the records of 58 patients treated with prostate cryoablation from October 2005 through April 2009 was conducted. Multivariate analysis of patient age, presenting prostate-specific antigen level, Gleason score, clinical T stage, prostate volume, maximum low temperature thermocouple recordings, history of radiation and or hormonal therapy, were studied as possible correlative factors for altered postoperative voiding function.Results: Of 58 patients, 22 (37.9%) manifested postcryoablation urgency and frequency (n = 13) requiring medical therapy or retention (n = 9). On multivariate analysis, age (P = .037) and an external sphincter temperature ≤ 23°C (P = .012) were associated with voiding frequency, urgency, or retention (odds ratio = 6.26, 95% CI: 1.62-24.16), whereas anterior rectal wall temperature (Denon) was weakly associated (P = .079).Conclusions: Thermocouple data provide an objective means of assessing cryosurgical outcomes. This is the first report of a correlation of such data to post-treatment voiding function. A total of 37.9% of patients experienced urgency and/or frequency or urinary retention after cryoablation of the prostate for localized disease. Older age and external sphincter temperature ≤ 23°C were statistically significant predictors of these events. The data suggest that limiting the degree of freezing at the external sphincter may decrease procedure related morbidity. Further study is warranted to better delineate temperature-related data on treatment outcomes.

Editorial Comment

Oscar Eduardo Fugita — 2010-02-01

The authors performed a retrospective review to identify possible correlative factors that may alter the postoperative voiding function after prostate cryoablation. This is an interesting approach to this technology as it is gaining more acceptance. However, some major limitations may hinder the interpretation of the results of the article. First, the lack of a standardized voiding symptom questionnaire does not allow a consistent evaluation of the provided data. The asked questions are too vague and cannot be objectively analyzed. Second, the thermocouple placement is a key factor to determine whether the measured temperature is effectively being measured at the external sphincter. If this is not true, all the conclusions of the article may be questionable. As far as I am concerned, positioning of the thermocouple catheters in and around the prostate is still a drawback of the cryoablation technique. Third, there is no data on patients' comorbidities that may be responsible for some of the symptoms and signs of voiding dysfunction, such as Parkinson and diabetes. Also, there is no data on pretreatment evaluation of postvoid residual volume. A high postvoid residual volume could already be present before treatment!

Reply

David A. Levy — 2010-02-01

The limitations mentioned in the reviewer's comments are valid and have been discussed in the manuscript. Careful preoperative questioning and available IPSS data minimized the likelihood of preoperative urinary retention; however, this remains a potential variable. As with any surgical procedure, some degree of inconsistency in technique is unavoidable. Nevertheless, the strength of this work is that as a single-surgeon series, variation in technique is minimized.