Urology
Volume 73, Issue 5, Supplement , Pages S28-S35, May 2009

Current Prostate Cancer Treatments: Effect on Quality of Life

Department of Urology, Jefferson Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania

Received 2 February 2009; accepted 6 March 2009.

Article Outline

Patients with prostate cancer (PCa) are presented with multiple therapeutic options. However, the evidence supporting a survival benefit with current PCa therapies is often limited and data directly comparing the available options are lacking. Although dramatic improvements have been made in the treatment methods available for PCa and there has been a decline in death rates for the disease, each active intervention has potential side effects and long-term complications that can adversely affect quality of life (QOL). The cancer diagnosis and management strategies can also negatively affect the QOL of patients and their families. The healthcare costs associated with cancer treatment are another factor to consider. When determining treatment options, patients and physicians should consider the efficacy of the therapy, as well as the safety, effect on QOL, and cost. As a part of a risk reduction strategy, effective screening programs, along with possible therapeutic agents, could have a positive effect on QOL and offer a preemptive benefit to patients at increased risk of PCa.

 

Prostate cancer (PCa) is the second most frequently diagnosed cancer among men and the sixth leading cause of cancer death in men worldwide. From the available global statistics, in 2007, an estimated 782 600 new cases were diagnosed and 254 000 patients died of PCa.1 The number of patients with PCa is increasing and, according to the rates from 2003 to 2005, it has been estimated that 15.78%, or 1 in every 6 men, will be diagnosed with PCa at some point during his lifetime.2 In the United States, the 5-year survival rate is approximately 31% for patients with metastasized PCa at diagnosis, and the survival rate approaches 100% for patients with localized cancer.3 Although the newly diagnosed patient is usually presented with a variety of treatment options, long-term active therapeutic intervention for PCa is associated with frequent adverse consequences. The most frequently reported side effects of treatment for localized PCa include incontinence, bleeding, gastrointestinal toxicity, and erectile dysfunction.4 These considerations, in addition to the emotional burden of the disease, can have a profound and long-term effect on patients' quality of life (QOL). This review provides the clinician with an overview of the most commonly used PCa treatments, with a focus on side effect profiles, QOL, and economic burden.

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Therapeutic interventions for PCa 

Success Rates of Current Therapies 

Depending on the disease stage, the primary treatment of PCa includes radiotherapy (RT), radical prostatectomy (RP), transperineal brachytherapy, cryotherapy, high-intensity focused ultrasound (HIFU), and androgen-deprivation therapy. Active surveillance is also gaining popularity. An overview of the most current recommendations from the American Urological Association and the U.S. National Comprehensive Cancer Network for the clinical management of PCa is given in Table 1.4, 5 Similar recommendations were published by the European Association of Urology in 2007.6 A head-to-head comparison of the efficacy of current PCa therapies has been limited by the lack of data. To date, RP is the only treatment of localized PCa that has shown improved cancer-specific survival in a prospective, randomized trial compared with another monotherapy (watchful waiting).7 Multimodality trials have demonstrated a survival advantage when hormonal therapy has been added to RT in the setting of high-risk disease.8 Going forward, the use of risk-adapted assessments of patients with newly diagnosed localized disease will aid in determining the best treatment options. This approach should now be standard in counseling men concerning their treatment options.9

Table 1. Therapeutic options for prostate cancer by risk groups based on American Urological Association and U.S. National Comprehensive Cancer Network guidelines
Risk Level4, 5AUA Guidelines4NCCN Guidelines for Initial Therapy5
Clinically localized
Low risk
PSA ≤10 ng/mL (AUA) or <10 ng/mL (NCCN) and Gleason score ≤6 (both) and clinical stage T1c or T2a (AUA) or T1-T2a (NCCN)
Active surveillance

RT (EBRT or IPB)

RP


Active surveillance

RT (EBRT or IPB)

RP (only if life expectancy ≥10 y)

Intermediate risk
PSA >10-20 ng/mL (AUA) or 10-20 ng/mL (NCCN) or Gleason score 7 (both) or clinical stage T2b but not qualifying for high risk (AUA) or T2b-T2c (NCCN)
Active surveillance

RT (EBRT or IPB)

RP


Active surveillance (only if life expectancy <10 y)

RT (EBRT ± IPB)

RP

High risk
PSA >20 ng/mL or Gleason score of 8-10 (both) or clinical stage T2c (AUA) or T3a (NCCN)
Active surveillance

RT (EBRT or IPB)

RP

(note: recurrence rates are high, and high risk of disease progression and death from prostate cancer might make active treatment a preferred option)


RT (EBRT) + ADT (long- or short-term)

RP (for selected patients)

Locally advanced
Very high risk (T3b-T4)NART (EBRT) + ADT
ADT
RP (for selected patients)
Metastatic
Any T, any NNAADT
RT (EBRT) + ADT (N1 patients)

AUA, American Urological Association; NCCN, National Comprehensive Cancer Network; PSA, prostate-specific antigen; RT, radiotherapy; EBRT, external beam RT; IPB, interstitial prostate brachytherapy (transperineal brachytherapy); RP, radical prostatectomy; ADT, androgen-deprivation therapy.

PCa can progress slowly and, with or without treatment, a large number of men can live many years after being diagnosed. However, only a few studies have indicated a survival benefit with currently available therapies. The potential adverse events and long-term complications associated with therapy are critical considerations in selecting treatment options.4 The major complications reported with RP, external beam radiotherapy (EBRT), and transperineal brachytherapy, the most common therapies for localized disease, are listed in Table 2.4 At 1 year after RP, the occurrence of erectile dysfunction can be as great as 60%-90%.4 Strategies are being investigated to reduce these rates; additional data have suggested that many men improve for ≤2 years after RP.10 Common additional complications of surgery include major bleeding (1.0%-12%), mild stress incontinence (4%-50%), severe stress incontinence (0%-15.4%), bladder neck obstruction (0.5%-15%), and urethral stricture (2%-9%).6 Whether the recent addition of robotic assistance to RP affects the overall performance of the surgical approach to PCa has been debated in published reports.11, 12

Table 2. Major complications reported with transperineal brachytherapy, external beam radiotherapy, and radical prostatectomy4
IPB (Transperineal Brachytherapy)EBRTRP
Bladder inflammation and obstruction, bleeding (varying levels), ED, GI/GU toxicity (varying degrees), stricture, urinary incontinence (any to severe)Bladder inflammation, bleeding (varying levels), ED, GI/GU toxicity (varying levels), fecal incontinence, stricture, ureteral injury, urinary incontinence (any to severe)Bladder obstruction, ED, bladder infection, stricture, urinary incontinence (any to severe), urine leak, fistula

ED, erectile dysfunction (insufficient for intercourse); GI, gastrointestinal; GU, genitourinary; other abbreviations as in Table 1.

Transperineal brachytherapy is associated with long-term erectile dysfunction (erectile dysfunction develops in about 40% of patients after 3-5 years), rectal morbidity (5%-21%), and chronic urinary complications (≤20%). Hematuria is common (≤100%) in the first few days after transperineal brachytherapy.4, 6 EBRT can result in erectile dysfunction rates as great as 80%.4 Diarrhea and loose stools affect 25%-50% of men and can linger for 2-3 years after EBRT.4 Studies have indicated that ≤39% of men experience rectal pain in the first year after EBRT. Patients who underwent EBRT commonly experienced urinary symptoms early after therapy. Moderate (grade 2) or worse urinary incontinence has been documented as a late adverse event in 5.3% of patients.4, 6 Additional improvements in targeting the prostate with techniques such as intensity-modulated RT might improve some of these RT side effects.13

The use of hormonal therapy is also associated with symptoms (Table 3)14, 15, 16, 17, 18, 19, 20, 21, 22 that range from significant morbidity (eg, osteoporosis, cardiovascular effects) to those that affect QOL (eg, fatigue, hot flashes).18 The direct and frequent consequences of anti-androgen hormonal therapy include erectile dysfunction (affecting 50%-100% of patients), gynecomastia (13%-70%), and hot flashes (55%-80%).14 With the increasing use of hormonal therapy for nonmetastatic PCa, long-term complications such as osteoporosis and cardiovascular risk factors become of increasing concern. A loss of cognitive function is also common and occurs in >50% of patients receiving hormonal therapy.14

Table 3. Reported incidence of adverse effects from hormonal therapy for prostate cancer
Adverse EffectIncidenceComment
Anemia13% with >25% decrease in hemoglobin14Normocytic normochromic14
Cognitive decline≥50%14, 15Decline in memory, attention, executive functions15
DepressionUnknown14If susceptible, might develop resistance, severe16, 17
Erectile dysfunction/libido loss50%-100%14Intermittent therapy might minimize effect18
Fatigue/general weakness13%14Significant increase with 3 mo of therapy14
Gastrointestinal symptomsVaries by agent14More common with combination hormonal therapy14
Gynecomastia40%-70% with anti-estrogens; 13% luteinizing hormone-releasing hormone14Becomes permanent after prolonged therapy14
Bone fractures, hormonally relatedUnknown18, 19Increased rate evident after 1 y of therapy14; bisphosphonates might reduce risk20
Hot flashes50%-80%1427% report most troublesome adverse effect14
Lipid abnormalitiesFrequent14Increased total cholesterol 11%; triglycerides 27%14
Osteoporosis1.4%-4.6%14, 21Osteopenic to osteoporotic, 36% after 1 y; 62% after 2 y18; more likely with continuous vs intermittent therapy22; might be reduced with bisphosphonates20
Weight gain/redistributionFrequent14Muscle wasting; increased fat deposition14

Alternative therapeutic options for patients with clinically localized PCa include high-dose-rate transperineal brachytherapy, proton beam therapy, cryosurgical ablation of the prostate, and HIFU. Data on the long-term outcomes in terms of cancer control are not yet substantial; these treatments are therefore not yet widely used and were not included in the standard treatment recommendations of major organizations such as the American Urological Association, European Association of Urology, or U.S. National Comprehensive Cancer Network.5, 6, 23 These newer therapies can be associated with unique side effect profiles. For example, cryotherapy is associated with erectile dysfunction (≤80%), urinary incontinence (5%-11%), tissue sloughing (3%-11%), and pelvic pain (1.4%-6%).6, 24 HIFU is associated with transient urinary retention in essentially all patients, and about 12% develop mild urinary stress incontinence. Erectile dysfunction occurs in 55%-70% of HIFU patients.6

The adverse consequences of PCa treatment can be significant, affecting almost every patient at some point during therapy, and more aggressive treatment options increase the likelihood of treatment complications and side effects.18 The use of combination therapy, although of proven benefit for specific groups of patients, is becoming more widespread and could further increase the incidence and scope of treatment-associated complications that patients might experience.25 Multimodality therapy shows significant decreases in QOL in most regimens, but especially with combined RT and transperitoneal brachytherapy.25 These adverse events affect the patient's QOL, in addition to burdening the healthcare system in terms of management costs and reduced patient function.

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QOL issues 

Although the very encouraging decrease in the PCa death rate can be attributed to the widespread use of prostate-specific antigen (PSA) screening, earlier treatment, and improved therapeutic options,1, 18 these factors can, ironically, adversely affect an individual's well-being. Because the optimal treatment of an individual patient with PCa cannot be definitively determined, the effect of each approach on QOL is an important consideration in individualizing PCa treatment. For example, more attention needs to be given to pretreatment dysfunction in helping prevent a “mismatch” of relatively contraindicated therapies for a specific patient.26 These mismatched patients have the most adverse QOL outcomes. In a survey of a prospective cohort that had begun treatment for early PCa 4-8 years earlier, the perceptions of cancer control, quality of treatment choices, and other elements of QOL, as well as treatment-related bowel, sexual, and urinary dysfunction, were studied. Most of the men stated they were confident in the cancer control achieved and the decisions they had made, but many stated they had doubts about one or both. The perception that their cancer had been controlled was lower in those men who had adverse medical factors, including secondary androgen ablation therapy, subsequent increases in PSA, and greater pretreatment Gleason scores. The men's confidence in their treatment decisions was not related to these factors, however. Instead, it was greater in the men who had chosen brachytherapy or RP, in those who stated they had paid close attention to their current PSA level, and in those who were married and who maintained a high level of masculine self-esteem.27

Potential Effect of PSA Screening and PSA Monitoring During Treatment on QOL 

For most men, an elevated PSA level is the first indication that they might have PCa. In addition, PSA levels are used to monitor the treatment effect. PSA screening and monitoring can adversely affect patients' anxiety levels and, consequently, their QOL. Therefore, one must carefully consider, in these settings, the effect of anxiety on an individual. Carlsson et al.28 evaluated the anxiety levels of 1781 men who were taking part in the European Randomized Study of Screening for Prostate Cancer.28 The anxiety levels were assessed while the men awaited clinical examination for a PSA level of ≥3 ng/mL. Initially high levels of anxiety were noted in <5% of men, suggesting that PCa screening is associated with generally low-to-moderate anxiety, except for a small proportion of susceptible men. This confirmed the results seen for colorectal cancer screening by colonoscopy.29 However, the negative effect of PSA screening could be significant for those who receive false-positive results. PSA levels are elevated (≥4.1 ng/mL)30 in approximately 66%-89% of men who subsequently have no evidence of PCa by biopsy.31 Katz et al.31 evaluated the potential effect on psychological well-being of these false-positive screening tests in 109 men with an abnormal PSA test or abnormal digital rectal examination findings but negative biopsy results. The men who had false-positive results were more likely to score below the mean score on the Short-Form 36-item Health Survey (SF-36) for the median population than were controls, but none of the differences were statistically significant. Those with false-positive results did not score significantly differently than controls on the State Anxiety Index, short-form version, or the SF-36 mental health subscales. When patients who had had a false-positive results were asked about PCa, however, they were significantly more worried than were controls about getting the disease (P = .0001). The PSA values do not explain these findings. Among those with false-positive results whose PSA data were available, the mean worry score was 4.0, 3.7, and 4.0 in the lower, middle, and upper tertiles of the PSA values, respectively (P = .41). The results were similar in the controls. Those with the experience of having a false-positive result also considered themselves to be significantly greater risk of PCa than did the controls (P = .001). Only 40% of the patients with false-positive results stated they believed that their PCa risk was very low (≤1:100) compared with 60% of controls, who thought their likelihood very low.31 PSA screening does not seem to have a significant effect on the QOL of most men who undergo the test before any diagnosis of PCa. False-positive results might contribute to a significant decrease in QOL and effective counseling interventions are recommended before PSA testing, before PCa screening, and during follow-up.31

Effect of Diagnosis and Disease Severity on Patient QOL 

Increased anxiety is common with a diagnosis of PCa.32, 33 Understanding the specific domains of well-being affected by the diagnosis can help healthcare professionals moderate the negative effects.34 Love et al.32 conducted a prospective QOL evaluation of 367 men newly diagnosed with either early or advanced PCa compared with a PCa-free, age-matched comparison group of men (n = 169). The diagnosis of PCa had a significant, negative effect on vitality, social functioning, role-emotional, and mental status, as measured by the SF-36. Additionally, a greater rate of anxiety was seen in men diagnosed with early-stage (5.2%) and advanced-stage (5.8%) PCa compared with aged-matched controls. Similarly, Rosenfeld et al.33 showed that the more advanced the stage of PCa, the greater its effect on global health-related QOL outcome measures, as determined by the Functional Assessment of Cancer Therapy (FACT) scale. The effect on QOL was independent of the symptoms and disability associated with advanced PCa. Strategies that might slow the progression of disease could not only control symptoms and improve patient function, but also improve the patient's QOL, making the early recognition of PCa risk even more important.

Effect of Patient Treatment Options on Patient QOL 

Considering the slow growth rate of PCa and its high prevalence in older men with a relatively short life expectancy, many patients diagnosed with PCa might have the option of active surveillance (or watchful waiting).6, 35 Although no adverse events are associated with active surveillance that would have a direct negative effect on QOL, cancer “worry” among men who opt for active surveillance has been documented in men with PCa.36 A study by Arredondo et al.37 revealed that, at baseline, men with PCa who chose watchful waiting had health-related QOL outcomes better than, or similar to, those of men without PCa at the beginning of the study. At the final study analysis, the men under watchful waiting had significant decreases observed with time in 7 domains of the SF-36 and 4 of the University of California, Los Angeles, Prostate Cancer Index scales. Many scores were affected significantly by increasing age and decreased over time; the physical domain scores and sexual function scores, however, decreased more than would have been expected from the aging process alone (P = .0001).37 Therefore, although active surveillance has tangible benefits, it can also have an effect on QOL, and additional research is needed to define the specific QOL domains affected. The Phase III Study of Active Surveillance Therapy Against Radical Treatment in Patients Diagnosed With Favorable-Risk Prostate Cancer (START) trial, sponsored by the National Cancer Institute, will compare the disease-specific survival of patients who have favorable-risk PCa treated with RP or radical RT at the initial diagnosis with that of patients whose treatment is active surveillance and selective intervention. In addition to cancer-related outcomes, the study will use a number of QOL instruments to further examine the QOL problems these different approaches might involve.38

Several case series and trials have shown that the treatment options for PCa consistently have a significant negative effect on multiple QOL domains.36, 39, 40, 41, 42 In a retrospective study of 287 men, those who were treated with RT or chemotherapy, or a combination of the 2, had greater levels of depression at the beginning of treatment compared with patients who underwent surgery.41 In another study of 730 men from the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry, health-related QOL was analyzed after treatment of localized PCa with RP, transperineal brachytherapy, or EBRT. The treatment-related symptom scores, such as sexual, urinary, and bowel function scores, had significantly worsened from baseline to 1 year later at the post-treatment follow-up visit. After treatment, men reported worse physical health-related QOL, and an average of 5.1 new symptoms were seen. A positive correlation was noted between a greater number of post-treatment symptoms and worse mental health (P < .01).36 These findings were further supported in an evaluation of 783 men with localized PCa who were participants in the Health Professionals Follow-up Study.42 However, these evaluations were limited owing to the lack of long-term follow-up. Newer therapies (eg, cryotherapy, HIFU) were not assessed, and such assessments will be necessary to assist patients and healthcare professionals in selecting appropriate treatment options.4, 39

Two well-designed, prospective, comparative QOL studies of modern treatment options have been published. A single-site study by Eller et al.43 examined 159 men with localized PCa and compared the health-related QOL outcomes after RP with those after 1 of 2 RT protocols. Although the 3 groups varied significantly in several key baseline characteristics, this short-term study demonstrated that baseline psychosocial characteristics, such as depressive symptoms, were stronger predictors of post-treatment QOL than treatment type.43 In the largest prospective study to date of QOL in PCa treatment, Sanda et al.39 measured the outcomes of 1201 patients with previously untreated Stage T1 or T2 PCa who had elected to undergo RP, transperineal brachytherapy, or EBRT. The participants were surveyed by telephone before and up to 24 months after the start of treatment, and the self-reported outcomes of the patients' partners (n = 625) were also assessed. Health-related QOL was evaluated primarily in the domains of sexual function, urinary incontinence, urinary irritation or obstruction, urinary function, bowel or rectal function, and vitality or hormonal function (Table 4). Each of the 3 treatments showed a distinct pattern of change in QOL, with the change in sexual QOL from baseline to follow-up significantly affected by each treatment (P < .001 for each comparison).39 Compared with baseline, urinary incontinence was significantly worse (P < .01 for each point) at each post-treatment assessment after RP for and after transperineal brachytherapy combined with RT, hormonal therapy, or both therapies. Large prostate size and hormonal therapy were associated with greater urinary irritation after transperineal brachytherapy or RT, but a large pretreatment prostate size was associated with an improvement in urinary irritation after prostatectomy. RT and transperineal brachytherapy were associated with an adverse effect on bowel function, beginning early in therapy that persisted for ≥1 year.39 Vitality and other hormone-related outcomes were worse after RT or transperineal brachytherapy in patients who had also undergone hormonal therapy.

Table 4. Quality of life outcomes associated with different therapeutic interventions
Therapeutic InterventionQOL Outcome
RT (IPB or EBRT)Greater level of depression41
Lower sexual function score36, 39
Lower urinary function score36, 39
Lower bowel function score36, 39
Lower physical health-related QOL36
Lower hormonal/vitality function39
ChemotherapyGreater level of depression41
RPLower sexual function score36, 39
Lower urinary function score36; lower urinary
incontinence score, but improved urinary irritation or obstruction symptoms39
Lower bowel function score36
Lower physical health-related QOL36
Combination therapy: RT + chemotherapyGreater level of depression41
Combination therapy: RT + hormonal therapyExacerbated sexual AEs39
Exacerbated hormonal/vitality AEs39

AE = adverse event; QOL = quality of life; other abbreviations as in Table 1.

These prospective studies have substantiated the findings from clinical case series: all active treatment options for PCa have a profound negative effect on a patient's QOL (Table 4). It is important to consider these long-term consequences of treatment before deciding on a cancer management plan.

QOL for Family Members and Caregivers 

Recent studies have revealed that the treatment of PCa also has a negative effect on family members and caregivers. Changes in each of the 5 QOL domains as measured by the Expanded Prostate Cancer Index Composite (EPIC) were seen in both patient and partner.39 Multivariate analyses showed that symptoms related to sexual function (P < .001), vitality (P = .004), and urinary function (P = .002) were independently associated with outcome satisfaction in the patients. Distress related to the sexual function domain negatively affected the partner at a highly significant statistical level (P < .001).39 The partner's QOL was directly associated with the patient's level of satisfaction with the treatment outcomes.39 In another study of patients undergoing RT for PCa, female family caregivers (n = 60) demonstrated clinically meaningful rates of depression (41%), anxiety (15%), pain (37%), sleep disturbance (33%), and morning fatigue (30%) that had a negative effect on their functional status and QOL.44 The consequences of caring for a patient with PCa can be significant, and the effect on the QOL of the caregiver can extend to the quality of care provided.

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Healthcare costs of PCa and QOL 

Healthcare costs are an important consideration in assessing the effect of PCa on society, and the costs can have a direct effect on patients' QOL. Although a comprehensive review of the cost of PCa was beyond the scope of this review, it is worth noting a few cost-related facts. The average per-patient cost in the first 6 months after diagnosis is approximately $11 495 (2004 U.S. dollars).45, 46, 47 Among men of all ages during a 15-year period, the lifetime costs of PCa treatment were $62 068 per person-year for all stages of the disease (1992 U.S. dollars).48 Among men ≥65 years, during an average of 7 years, the costs of PCa treatment were $48 684 per diagnosed person from diagnosis to death (1990 U.S. dollars).49, 50 To manage the adverse effects of many of the current therapies for PCa, patients may require additional medications or additional physician time, which adds to the cost. Although no studies are available to quantify the effect, the significant total costs associated with PCa care can be expected to have negative consequences on a patient's QOL.

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Benefit of reducing risk of developing PCa 

One focus in the field of PCa is determining the optimal management strategy for an individual patient. Factors such as overall health, life expectancy, disease characteristic, and patient expectations are all important to consider. With the growing interest in PCa prevention strategies, reducing the risk of PCa is now developing its own unique management strategy. The question of whether a risk-reduction strategy will affect patients' QOL is not yet answered. However, the benefits of reducing the risk of developing PCa are evident: avoiding the safety burden of long-term therapy, avoiding the QOL issues associated with the disease and its treatment, and avoiding the costs associated with therapy and disease management. The high incidence coupled with a typically late age of onset make PCa a rational target for risk reduction.23

Although many agents are under investigation, the current major clinical trials in PCa prevention have focused on vitamin E, selenium, and 5α-reductase inhibitors (5ARIs). The results of the Selenium and Vitamin E Cancer Prevention Trial (SELECT) on the prevention of PCa in >35 000 men have been recently reported. However, neither selenium nor vitamin E, alone or in combination, at the dosages and formulations used, was able to prevent PCa in this population of relatively healthy men.51 Treatment with a pharmacologic agent such as a 5ARI might reduce the risk of PCa development and subsequent treatment of the disease. 5ARIs are already being used for the treatment of benign prostatic hyperplasia.52, 53 The Prostate Cancer Prevention Trial was the first large prospective randomized clinical trial to demonstrate a reduced risk of PCa with a specific therapeutic intervention. The Prostate Cancer Prevention Trial demonstrated a PCa detection rate of 18.4% in patients taking a 5ARI, finasteride (which inhibits only type 2 5α-reductase) compared with 24.4% in patients taking a placebo, yielding a relative risk reduction of 24.8%.54 More men in the finasteride arm of the trial developed aggressive histologic cancer than did those in the placebo arm. The initial concerns regarding the development of more aggressive histologic PCa in some men in the trial have been addressed extensively in published reports. The Reduction by Dutasteride of Prostate Cancer Events (REDUCE) study is ongoing and was designed to evaluate whether the more potent 5ARI dutasteride (which has both type 1 and 2 5α-reductase specificity) decreases the future incidence and progression of PCa in a high-risk patient population.55 In clinical trials, 5ARIs have been shown to be safe and well tolerated: the most common drug-related adverse events reported were erectile dysfunction (7% vs 4% in placebo), decreased libido (4% vs 2% in placebo), gynecomastia (2% vs <1% in placebo), and ejaculation disorders (2% vs <1% in placebo).56 Moreover, the incidence of adverse events declined significantly within 1-4 years of treatment, indicating the transient nature of the treatment adverse effects.57, 58 No significant differences were found for serious adverse events between finasteride and placebo.58 This would indicate that the effect on QOL with the use of these agents would be much less than the effect of many therapies for diagnosed PCa discussed previously. The recently released guidelines from the American Urological Association and the American Society of Clinical Oncology have recommended that 5ARIs be more widely used as a risk-reduction strategy.59 The effect of this strategy on the QOL for an individual patient must be considered by the clinician.

A recent analysis evaluated the cost-effectiveness of therapy with a 5ARI, taking into account the potential improvement in QOL.60 Compared with no treatment, the quality-adjusted cost-effectiveness ratio for risk reduction with the 5ARI was $122 747 per quality-adjusted life-year saved. This model found chemoprevention with finasteride to increase the quality-adjusted life-years by 29 days per individual, corresponding to a gain of 74 quality-adjusted life-years per 1000 men.60 Although this might seem a small gain, it is not insignificant. In terms of prevention strategies, the differences in life expectancy are often no more than a few weeks or days because the gains are averaged across the entire target population. An examination of other prevention strategies puts these numbers into perspective. Childhood immunizations for measles, rubella, and pertussis each increase life expectancy by 0.1 month. Cost-effective modeling for breast cancer chemoprevention found tamoxifen increases the survival outcomes by 42 days for women 50 years old and 27 days for those 60 years old. The cost-effectiveness of a chemopreventive agent depends on the baseline risk of the population that receives it.60 The investigators concluded that a therapeutic intervention can be cost-effective in high-risk populations when the effect on QOL is considered.60 Thus, assessing future risk and implementing a risk-reduction strategy could help forego some of the issues associated with PCa diagnosis and treatment, such as the adverse effects, QOL, and the resulting economic burden. When using these potential chemoprevention agents, QOL must likewise be considered.

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Conclusions 

PCa is a prevalent disease among men. Despite a wide array of therapeutic choices, limited data are available to indicate a clearly defined survival benefit with most current therapies. Although significant improvement has occurred in the outcomes of many treatments of localized PCa, a number of significant adverse effects, which have a considerable effect on patients and their families, are associated with definitive treatment. The mere diagnosis of PCa and active surveillance strategies can also negatively affect patients' QOL. Therefore, the patient and physician need to carefully consider, not only the efficacy, but also the consequences of each treatment option, including the potential adverse effects and effect on QOL. PSA screening has improved the detection of PCa at earlier stages, with a low effect on QOL and with a probable effect on survival. Cost-effective risk reduction strategies such as early screening tests and the use of interventional pharmacologic agents might have the potential to reduce the future incidence and burden of PCa among high-risk patients.

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 L. G. Gomella serves as a consultant and investigator for GlaxoSmithKline and as a consultant to Watson Pharmaceuticals; E. J. Trabulsi serves as a paid consultant to Intuitive Surgical; J. Johannes has no conflicts to report.

PII: S0090-4295(09)00316-1

doi:10.1016/j.urology.2009.03.003

Refers to erratum:

Urology
Volume 73, Issue 5, Supplement , Pages S28-S35, May 2009

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