Objective
To evaluate the effectiveness of UPOINT based multimodal treatment on patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), and determine factors that could be associated with clinical improvement.
Methods
A retrospective study was conducted in Doha, Qatar including patients with CP/CPPS from the Middle East and North Africa. The UPOINT phenotyping system was used to classify patients and guide their multimodal therapy. NIH-CPSI scores were computed initially and after 3 months of treatment, and predictors of clinical improvement were assessed.
Results
The total NIH-CPSI improved significantly with a mean reduction of 8.21 after 3 months of treatment (P < .001). 66.2% of patients had a clinical improvement demonstrated as a total NIH-CPSI score reduction by at least 6 points after 3 months of treatment. No significant association was found between clinical improvement, and extent of pain (ORa = 1.198, 95% CI 0.392-3.662, P = .751), initial total NIH-CPSI (ORa = 0.983, 95% CI 0.886-1.089, P = .738), number of positive UPOINT domains (ORa = 0.871, 95% CI 0.451-1.681, P = .681), and number of prescribed therapies (ORa = 1.118, 95% CI 0.699-1.789, P = .641).
Conclusion
UPOINT phenotyping and directed therapy is associated with an important improvement in the CP/CPPS. Therapeutic response does not appear to related to age or ethnicity. Clinical improvement is also not predicted by initial extent and severity of the disease, whether relating to NIH-CPSI or the number of positive UPOINT phenotypes, neither to the number of therapies involved in the multimodal treatment strategy.
Chronic prostatitis (CP) is characterized by a wide range of clinical manifestations that substantially affects the quality of life (QoL). Four categories of prostatitis syndrome are identified by the National Institutes of Health (NIH) and include acute bacterial prostatitis (Category I), chronic bacterial prostatitis (Category II), chronic nonbacterial prostatitis or chronic pelvic pain syndrome (CP/CPPS) (Categories IIIA and IIIB), and asymptomatic inflammatory prostatitis (Category IV).
1
The third category of CP or CP/CPPS is a common disorder with a prevalence ranging between 2.2% and 13.8%. It frequently affects men who are younger than 50 years of age, though the exact etiology remains poorly understood.
2
The disease appears to be multifactorial in origin and has a divergent spectrum of clinical presentations that commonly manifest as chronic pain alongside voiding difficulties, erectile and ejaculation dysfunction, and psychiatric symptoms.3
Consensus guidelines divide CP/CPPS into an early stage characterized by persistent or recurrent symptoms for less than 6 months with no previous use of antibiotics, and a late stage characterized by persistent or recurrent symptoms for more than 6 months that are refractory to first line treatment.4
CP/CPPS is a diagnosis of exclusion, hence all other etiologies of a patient's pain and lower urinary tract symptoms (LUTS) such as stones, tumors, and strictures must be assessed and treated when possible.
4
The disease care process is complex and clinical outcomes are usually not satisfactory, owing to the heterogenous nature of symptoms between patients and insufficient specific diagnostic markers.5
,6
In fact, routine management models are not specifically defined and the CP/CPPS generally fails monotherapy due to the variable disease etiology and clinical progression. Consequently, clinical phenotyping and individualization of the therapy are highly suggested.7
The urinary, psychosocial, organ‑specific, infection, neurological/systemic and tenderness (UPOINT) phenotype system was developed in 2009 by Shoskes et al. as a novel diagnostic and therapeutic algorithm to classify CP/CPPS and establish multimodal phenotype-based treatment plans.
5
The UPOINT system is composed of 6 domains that provide a phenotyping algorithm based on the urinary manifestations, psychosocial abnormalities, organ‑specific symptoms, infection-related symptoms, neurological/systemic dysfunction, and skeletal muscles’ tenderness. The patient symptoms and disease progression are linked to each domain to provide a clinical diagnosis and recommend a phenotype specific therapy.8
Several studies validated the UPOINT system and showed that the number of positive domains in the system correlate with increasing NIH-Chronic Prostatitis Symptom Index (NIH-CPSI).
9
, 10
, 11
, 12
The UPOINT-based phenotyping and directed therapy was reportedly associated with substantial improvement in the CP/CPPS symptoms.10
Nevertheless, literature on the determinants of a UPOINT-based therapy outcomes remains scarce and very limited data are available especially from Middle East and North Africa. This was a retrospective study that aimed to: (1) evaluate the effectiveness of the CP/CPSS therapy based on the UPOINT phenotype classification system; and (2) determine factors that could predict the clinical improvement of symptoms following multimodal therapy.METHODS
Study Design and Participants
A retrospective study was conducted at the pelvic pain unit of the urology department at Hamad Medical Corporation (HMC), Doha, Qatar. The pelvic pain unit was established in August 2016 and, to the best of our knowledge, is the first to provide a dedicated multidisciplinary service for patients with chronic pelvic pain in the region. Management is offered by a Urologist, Physiotherapist and Psychiatrist with special interest and expertise in this field of medicine. Patients with CP/CPPS who were diagnosed according to the NIH consensus guidelines for diagnosis of CP/CPPS were included.
13
While patients with other pre-diagnosed forms of prostatitis that may overlap with the clinical manifestations of CPPS including acute bacterial prostatitis, chronic bacterial prostatitis, and asymptomatic prostatitis were excluded. Additional exclusion criteria were patients with evidence of antibiotic use within 2 weeks of their presentation, those who underwent previous prostate surgery or who have an active prostate cancer. The dates of diagnosis of these conditions were verified against the medical profiles of the patients to preclude any risk of selection bias. The institutional review board at HMC approved the study protocol (protocol No. MRC-01-21-004), and methods were enacted according to the institutional guidelines and regulations. A waiver of signed informed consent was used.Procedures and Variables
All patients were thoroughly evaluated with history and physical examination. The initial NIH-CPSI score was computed at the baseline. Pain was characterized according to its location, description, triggering factors, and number of locations involved. All psychosocial symptoms relating to pain, stress, anxiety, depression, somatization symptoms, social aspects, substance abuse, personality factors, trauma-related disorders, and QoL were assessed and evaluated. LUTS were evaluated and infections were determined by culturing expressed prostatic secretions (EPS). Bladder and prostatic specimens were also evaluated by assessing midstream urine (VB2), and first 10 mL of voided urine after EPS (VB3). Anatomical and pathological abnormalities were determined by flexible cystoscopy when indicated, and calcifications were examined by transrectal ultrasonography (TRUS). The UPOINT phenotyping system was used to classify the patients and guide their multimodal therapy. Pharmacological and non-pharmacological treatments included alpha blockers, antibiotics, antidepressants, anticholinergics, neuroleptics, phytotherapy, physical therapy, low intensity extracorporeal shockwave therapy (Li-ESWT), and mental health therapy. NIH-CPSI score was computed after 3 months of treatment, and clinical improvement was determined by a total score decline of at least 6 points.
14
Statistical Analysis
Data were analyzed by IBM Statistical Package for the Social Sciences (SPSS, version 25). The demographic, clinical, and therapeutic characteristics of patients were evaluated by descriptive statistics. Continuous variables were assessed by their mean ( ± standard deviation, SD), and median (interquartile range, IQR). Categorical variables were assessed by their frequencies and percentages. The Shapiro-Wilk test was used to assess the normal distribution of variables. A paired sample T-test was used to compare the NIH-CPSI scores at baseline and after 3 months of treatment. The mean index difference was dichotomized at a score of 6 to evaluate clinical improvement. Multivariable logistic regression using enter method was run to determine the demographic and clinical predictors of improvement. The results were reported as adjusted odds ratio (ORa) and 95% CI. P values of .05 and less were considered statistically significant with an acceptable margin of error of 5%.
RESULTS
Demographic and Clinical Characteristics of Patients
A total of 193 patients were included in the study. The mean age was 39.68 ( ± 10.15), 55.4% were from Middle East, the median duration of illness was 18 months, and 45.6% had psychosocial symptoms. More than the half (69.9%) had irritative LUTS, 6.7% had calcification on TRUS, and 13% had abnormal result on flexible cryptoscopic examination. Around one-third of the patients (32.1%) had positive cultures of EPS, 15.8% had abnormal white blood cell (WBC) count in the bladder specimen, and 60.4% had abnormal WBC count in the prostatic specimen. The patients’ demographic and clinical characteristics are shown in Table 1.
Midstream urine specimen (bladder specimen).
Table 1Demographic and clinical characteristics of patients
| Characteristic | Frequency (%) or Mean ( ± SD)/ Median (IQR) |
|---|---|
| Age | 39.68 (10.15) |
| Region | |
| ▓ Middle East ▓ North Africa | 107 (55.4) 86 (44.6) |
| Duration (mo) | 18.00 (7.00-48.00) |
| LUTS | |
| ▓ Irritative ▓ Obstructive | 135 (69.9) 114 (59.1) |
| TRUS calcification | |
| ▓ Yes ▓ No | 13 (6.7) 17 (8.8) |
| Psychosocial symptoms | 88 (45.6) |
| Flexible cystoscopy | |
| ▓ Performed cases ▓ Normal result ▓ Abnormal result | 30 (15.5) 5 (2.6) 25 (13.0) |
| EPS result | |
| ▓ Negative culture ▓ Positive culture | 55 (67.9) 26 (32.1) |
| VB2 | |
| ▓ <5 WBC/HPF ▓ >5 WBC/HPF | 155 (84.2) 29 (15.8) |
| VB3 | |
| ▓ <5 WBC/HPF ▓ >5 WBC/HPF | 72 (39.6) 110 (60.4) |
† First 10 mL of voided urine after EPS (prostatic specimen).
Pain Characteristics
Greater than half of the patients had perineum pain (65.8%) followed by penile pain (49.2%). Pain was described as burning or compressing (33.7% and 30.1%) respectively. The pain was mostly triggered by ejaculation (63.2%) followed by urination (16.6%). For the extent of pain, around half of the patients had less than 3 pain locations. SupplementaryTable 1 reports the detailed pain characteristics of the patients.
UPOINT Phenotyping
Most of the patients (43%) had 2 UPOINT classification domains. The majority (81.3%) were classified with the organ confined phenotype, and 71% had the urinary phenotype. Around one-third of patients (34.2%) had tenderness, and 21.8% had psychosocial symptoms. The UPOINT phenotyping is reported in Table 2.
Table 2UPOINT phenotype classification
| Phenotype | Frequency (%) |
|---|---|
| Urinary | |
| ▓ No ▓ Yes | 56 (29.0) 137 (71.0) |
| Psychosocial | |
| ▓ No ▓ Yes | 151 (78.2) 42 (21.8) |
| Organ confined | |
| ▓ No ▓ Yes | 36 (18.7) 157 (81.3) |
| Infection | |
| ▓ No ▓ Yes | 165 (85.5) 28 (14.5) |
| Neurogenic | |
| ▓ No ▓ Yes | 181 (93.8) 12 (6.2) |
| Tenderness | |
| ▓ No ▓ Yes | 127 (65.8) 66 (34.2) |
| Number of positive UPOINT domains | |
| ▓ 1 ▓ 2 ▓ 3 ▓ 4 ▓ 5 | 38 (19.7) 83 (43.0) 51 (26.4) 20 (10.4) 1 (0.5) |
Multimodal Treatment Strategy
Both pharmacological and non-pharmacological therapies were prescribed in the UPOINT directed therapy. Around 60% of the patients were on alpha blockers and 35.2% were on antibiotics. Phytotherapy and physical therapy were prescribed and utilized by 44.6% and 20.7% respectively, and 33.7% of the patients had extracorporeal shock wave therapy (ESWT). Supplementary table 2 presents the full pharmacological and non-pharmacological therapies of the patients.
NIH-Chronic Prostatitis Symptom Index
The initial total NIH-CPSI score was 26.26 ( ± 6.57). The total score improved significantly with a mean reduction of 8.21 after 3 months of treatment (P < .001). The pain, urinary, and quality of life score of NIH-CPSI also significantly improved after 3 months with a mean score reduction of 3.97, 1.96, and 2.22 respectively. The paired sample T-test of the initial and 3-month NIH-CPSI is shown in Table 3.
Table 3Paired sample T-test of NIH-CPSI initially and after 3-month follow-up
| Symptom Index | Assessment | Mean | SD | Mean Difference | P value |
|---|---|---|---|---|---|
| Pain | Initial | 12.55 | 3.49 | 3.97 | < .001 |
| After 3 mo | 8.58 | 4.22 | |||
| Urinary | Initial | 5.71 | 2.83 | 1.96 | < .001 |
| After 3 mo | 3.75 | 2.86 | |||
| Quality of life | Initial | 7.82 | 2.23 | 2.22 | < .001 |
| After 3 mo | 5.60 | 2.65 | |||
| Total | Initial | 26.26 | 6.57 | 8.21 | < .001 |
| After 3 mo | 18.05 | 8.44 |
Predictors of Clinical Improvement
Greater than half of the patients (66.2%) had a clinical improvement demonstrated a total NIH-CPSI score reduction by at least 6 points after 3 months of treatment. Demographic and clinical characteristics of the patients were not significantly associated with clinical improvement. The extent of pain, initial NIH-CPSI, number of positive UPOINT domains, and number of prescribed therapies were also not significantly associated with clinical improvement. Table 4 presents the multivariable logistic regression of predictors of clinical improvement.
Table 4Multivariable logistic regression of predictors of clinical improvement
| 95% confidence Interval | P value | |||
|---|---|---|---|---|
| Variable | ORa | Lower | Upper | |
| Age | 1.008 | 0.947 | 1.072 | .812 |
| Region (Middle East vs North Africa) | 0.620 | 0.204 | 1.887 | .400 |
| Duration of disease | 1.003 | 0.993 | 1.013 | .544 |
| Pain extent (reference: >3 locations) | 1.198 | 0.392 | 3.662 | .751 |
| Initial Total NIH CPSI | 0.983 | 0.886 | 1.089 | .738 |
| Number of positive UPOINT domains | 0.871 | 0.451 | 1.681 | .681 |
| LUTS: irritative (No vs Yes) | 1.535 | 0.432 | 5.450 | .507 |
| LUTS: obstructive (No vs Yes) | 0.578 | 0.181 | 1.846 | .355 |
| Number of prescribed therapies | 1.118 | 0.699 | 1.789 | .641 |
DISCUSSION
The current study examined the impact of UPOINT phenotyping and multimodal therapy on the clinical outcomes of patients with CP/CPPS, and assessed predictors of clinical improvement. We found that a UPOINT classification and directed therapy is associated with a substantial improvement in the clinical outcomes. No significant associations between clinical improvement, and the demographic and clinical characteristics of the patients were determined. We also found no significant association between clinical improvement, and the disease severity according to pain extent, number of positive UPOINT domains, and number of prescribed therapies within the multimodal treatment strategy.
A UPOINT guided therapy improved the clinical outcomes and was associated with a significant reduction in the NIH-CPSI score. According to Propert et al therapeutic effect can be determined at a highly sensitive and specific 6-point reduction of the total NIH-CPSI score.
15
In the present study, greater than half of the patients were categorized as therapeutic responders whilst they achieved this perceivable score improvement. The response rate was slightly higher compared to other results from the Far East that determined clinical improvement at a 6-point score decline in exactly 50% of the patients.16
Although this study had higher initial pain, urinary, QoL, and total NIH-CPSI score compared to that study, our multivariable analysis showed that clinical improvement is not predicted by the initial total symptom index.CP/CPPS is commonly linked to ejaculatory pain or pelvic discomfort with conspicuous LUTS.
17
Our findings showed that CP/CPPS is largely described as burning and compressing, and extends to less than 3 locations primarily the perineum and penis. Fewer locations of pain involvement and irritative rather than obstructive LUTS appear to be associated with higher odds of response to multimodal therapy, however, this association was not statistically significant. Although this study included relatively younger patients compared to other studies,10
,18
, 19
, 20
our results do not appear to be confounded by age as the multivariable analysis showed no significant association between age and clinical improvement. Moreover, whilst having a heterogenous population from different regions, our findings suggest that ethnicity does not link to symptom index improvement. Therefore, we hypothesize no role of genetics in determining clinical response to CP/CPPS treatment.The multimodal therapeutic strategy in this study involved a blend of pharmacological and non-pharmacological treatments and depending mostly on alpha blockers. In a pooled analysis, alpha blockers were associated with a significant improvement of CP/CPPS symptoms.
21
This can be explained by the overlapping nature of the disease pathogenesis and over activation of alpha-adrenergic receptors, which warrant empirical utilization of alpha blocking agents in the management of CP/CPPS.22
Nevertheless, the utilization of any monotherapy is reportedly associated with insufficient response particularly when compared to multimodal strategies.23
Our findings add to the literature that clinical response to a UPOINT directed therapy is related to qualitative rather than quantitative multimodal strategies, as our multivariable analysis showed no significant association between the number of prescribed therapies and clinical improvement.Previous literature reported a significant strong correlation between the number of positive UPOINT domains and initial NIH-CPSI total score.
5
,18
, 19
, 20
We determined that patients could have greatly 2 UPOINT phenotypes. While the number of positive UPOINT domains is evidently linked to disease severity, the current study adds to the literature that the number of positive domains does not have a significant impact on the NIH-CPSI posttherapy score and therefore does not predict clinical improvement.Strengths and Limitations
No previous reports evaluated the utility of the UPOINT system on patients from Middle East and North Africa. The design of the study allowed to establish temporality of associations and thus determine causality. The sample size was adequate to allow for multivariable analysis to determine predictors of clinical outcomes while eliminating potential confounders. On the other hand, few limitations could be reported. The retrospective nature of the study can be considered as one limitation. The clinical outcomes were measured only after 3 months of treatment and therefore the current study did not determine long term predictors of maintaining clinical response. Further research is suggested in this context to follow-up patients over an extended 1- to 5-year period to assess long term fluctuations in NIH-CPSI with multimodal therapy, and evaluate factors that could be associated with favorable outcomes. In addition, residual confounders relating to sexual dysfunction cannot be precluded. Sexual dysfunction is common in 40% to 70% of the CP/CPPS patients, and can be associated with higher rates of depression and anxiety.
24
, 25
, 26
, 27
, 28
Addition of “sexual dysfunction” domain into the UPOINT system is still controversial.8
Future work will prospectively evaluate the use of the UPOINT plus “sexual dysfunction” system in the treatment of CP/CPPS.CONCLUSION
The UPOINT classification and directed therapy is associated with an important improvement in the symptoms and thus QoL over a sensitive and specific cutoff point of the NIH-CPSI. Therapeutic response does not appear to related to age or ethnicity. Similarly, clinical improvement is not predicted by initial extent and severity of the disease, whether relating to NIH-CPSI or the number of positive UPOINT phenotypes, neither to the number of therapies involved in the treatment strategy. This underscores the value of the UPOINT phenotype directed therapy as an approach associated with measurable significant improvement in patients’ symptoms.
Appendix. SUPPLEMENTARY MATERIALS
References
- Non-pharmacological interventions for treating chronic prostatitis/chronic pelvic pain syndrome.Cochrane Database Syst Rev. 2018; 2018 (Cochrane Urology Group, editor): 16
- The prevalence of prostatitis-like symptoms in China.J Urol. 2009; 182: 558-563
- Prostatitis/chronic pelvic pain syndrome.Annu Rev Med. 2006; 57: 195-206
- Diagnosis and treatment of chronic bacterial prostatitis and chronic prostatitis/chronic pelvic pain syndrome: a consensus guideline.BJU Int. 2015; 116: 509-525
- Clinical phenotyping of patients with chronic prostatitis/chronic pelvic pain syndrome and correlation with symptom severity.Urology. 2009; 73 ([discussion: 542-543]): 538-542
- Editorial comment.Urology. 2009; 73: 542
- Clinical phenotyping in chronic prostatitis/chronic pelvic pain syndrome and interstitial cystitis: a management strategy for urologic chronic pelvic pain syndromes.Prostate Cancer Prostatic Dis. 2009; 12: 177-183
- Using the UPOINT system to manage men with chronic pelvic pain syndrome.Arab J Urol. 2021; 19: 387-393
- Contemporary management of chronic prostatitis/chronic pelvic pain syndrome.Eur Urol. 2016; 69: 286-297
- Phenotypically directed multimodal therapy for chronic prostatitis/chronic pelvic pain syndrome: a prospective study using UPOINT.Urology. 2010; 75: 1249-1253
- Use of the UPOINT chronic prostatitis/chronic pelvic pain syndrome classification in European patient cohorts: sexual function domain improves correlations.J Urol. 2010; 184: 2339-2345
- Clinical utility of the UPOINT phenotype system in chinese males with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS): a prospective study.PLoS ONE. 2013; 8 (Thumbikat P, editor): e52044
- The NIH consensus concept of chronic prostatitis/chronic pelvic pain syndrome compared with traditional concepts of nonbacterial prostatitis and prostatodynia.Curr Urol Rep. 2002; 3: 301-306
- The three as of chronic prostatitis therapy: antibiotics, alpha-blockers and anti-inflammatories. What is the evidence?.BJU Int. 2004; 94: 1230-1233
- Responsiveness of the national institutes of health chronic prostatitis symptom index (NIH-CPSI).Qual Life Res Int J Qual Life Asp Treat Care Rehabil. 2006; 15: 299-305
- Clinical significance of National Institutes of Health Classification in patients with chronic prostatitis/chronic pelvic pain syndrome.Korean J Urol. 2014; 55: 276
- Clinical practice. Chronic prostatitis and the chronic pelvic pain syndrome.N Engl J Med. 2006; 355: 1690-1698
- Use of the UPOINT classification in Turkish chronic prostatitis or chronic pelvic pain syndrome patients.Urology. 2016; 97: 227-231
- Evaluation of a modification of the UPOINT clinical phenotype system for the chronic pelvic pain syndrome.Scand J Urol Nephrol. 2009; 43: 373-376
- Inclusion of erectile domain to UPOINT phenotype does not improve correlation with symptom severity in men with chronic prostatitis/chronic pelvic pain syndrome.Urology. 2011; 78: 653-658
- α-blockers, antibiotics and anti-inflammatories have a role in the management of chronic prostatitis/chronic pelvic pain syndrome.BJU Int. 2012; 110: 1014-1022
- Ciprofloxacin or tamsulosin in men with chronic prostatitis/chronic pelvic pain syndrome: a randomized, double-blind trial.Ann Intern Med. 2004; 141: 581-589
- Failure of a monotherapy strategy for difficult chronic prostatitis/chronic pelvic pain syndrome.J Urol. 2004; 172: 551-554
- Adverse impact of sexual dysfunction in chronic prostatitis/chronic pelvic pain syndrome.Urology. 2008; 71: 79-84
- Prevalence of sexual dysfunction in men with chronic prostatitis/chronic pelvic pain syndrome.Arch Ital Urol Androl Organo Uff Soc Ital Ecogr Urol E Nefrol. 2007; 79: 67-70
- Chronic prostatitis and erectile dysfunction: results from a cross-sectional study.Arch Ital Urol Androl Organo Uff Soc Ital Ecogr Urol E Nefrol. 2008; 80: 172-175
- Sexual and relationship functioning in men with chronic prostatitis/chronic pelvic pain syndrome and their partners.Arch Sex Behav. 2007; 36: 301-311
- Chronic prostatitis and depressive disorder: a three year population-based study.J Affect Disord. 2011; 134: 404-409
Article info
Publication history
Published online: May 05, 2022
Accepted:
April 24,
2022
Received in revised form:
April 23,
2022
Received:
February 28,
2022
Identification
Copyright
© 2022 The Author(s). Published by Elsevier Inc.
User license
Creative Commons Attribution (CC BY 4.0) | How you can reuse 
Elsevier's open access license policy
Creative Commons Attribution (CC BY 4.0)
Permitted
- Read, print & download
- Redistribute or republish the final article
- Text & data mine
- Translate the article
- Reuse portions or extracts from the article in other works
- Sell or re-use for commercial purposes
Elsevier's open access license policy
