Analysis of active surveillance uptake for localized prostate cancer in Quebec in 2016: A Canadian bicentric study and comparison with 2010 data.

INTRODUCTION: Active surveillance (AS) has emerged as a primary management strategy for low-risk prostate cancer (PC) patients. We aimed to assess AS uptake over a 1-year snapshot throughout Quebec and to compare it to 2010 multicentric Canadian data. METHODS: A retrospective chart review and data collection was performed in 1 academic and 2 non-academic community centres from Quebec, among men identified in 2016 with localized T1c-T2c PC on biopsy, fulfilling NCCN criteria of low-risk (LR)-PC, including very-low-risk (VLR) and non-VLR-PC, and favourable-intermediate risk (FIR)-PC. AS adherence was defined when chosen as initial strategy, without any radical treatment within 6 months. RESULTS: Overall, 259 patients fulfilled the inclusion criteria with 50.2% of VLR-PC patients. At 6 months, 81% patients in the LR group and 65% in the FIR group were considered as adherent to AS, in both centres, but with an increased use of AS in the community centres compared to 2010 data. The rates of AS maintenance decreased at 12 months to respectively 69% and 58%. Among the VLR group, the rate of initiation was 98% and decreased to 85% at 12 months. CONCLUSION: Our data suggest that the majority of low-risk PC patients indeed initiated an AS in 2016, with even a greater proportion of VLR-PC patients compared to 2010. This ideal strategy should be encouraged and improved at 12 months, and assessed with recent data and longer follow-up.

Trial Participation is Not Associated with Better Biochemical Recurrence-free Survival in a Large Cohort of External Beam Radiotherapy-Treated Intermediate- and High-Risk Prostate Cancer Patients.

AIMS: There is a widespread belief that outcomes of cancer patients treated within clinical trials might not be representative of the outcomes obtained within standard clinical settings. We sought to investigate the effect of trial participation on biochemical recurrence (BCR) in localised, D'Amico intermediate- and high-risk prostate cancer patients treated with external beam radiotherapy (EBRT). MATERIALS AND METHODS: We relied on a study population treated with EBRT between January 2001 and January 2021 at a single tertiary care centre, stratified according to trial enrolment. Separate Kaplan-Meier and multivariable Cox regression models tested BCR-free survival at 60 months within intermediate- and high-risk EBRT patients, after adjustment for covariables. Additionally, the analyses were refitted after inverse probability treatment weighting was performed separately for both risk subgroups. RESULTS: Of 932 eligible patients, 635 (68%) and 297 (32%) had intermediate- and high-risk prostate cancer, respectively. Overall, 53% of patients were trial participants. BCR rates were 11 versus 5% (P = 0.27) and 12 versus 14% (P = 0.08) in trial participants versus non-participants for intermediate- and high-risk subgroups, respectively. Differences in patient and clinical characteristics were recorded. Trial participation status failed to reach predictor status in multivariable Cox regression models for BCR in both intermediate-risk (hazard ratio 1.34; 95% confidence interval 0.71-2.49; P = 0.4) and high-risk patients (hazard ratio 1.03; 95% confidence interval 0.45-2.34; P = 0.9). Virtually the same results were recorded in inverse probability treatment weighting cohorts. CONCLUSIONS: Relying on a large cohort of EBRT-treated intermediate- and high-risk patients, no BCR differences were recorded between trial participants and non-participants after accounting for confounders.

The current role of precision surgery in oligometastatic prostate cancer.

Oligometastatic prostate cancer (omPCa) is a novel intermediate disease state characterized by a limited volume of metastatic cells and specific locations. Accurate staging is paramount to unmask oligometastatic disease, as provided by prostate-specific membrane antigen-positron emission tomography. Driven by the results of prospective trials employing conventional and/or modern staging modalities, the treatment landscape of omPCa has rapidly evolved over the last years. Several treatment-related questions comprising the concept of precision strikes are under development. For example, beyond systemic therapy, cohort studies have found that cytoreductive radical prostatectomy (CRP) can confer a survival benefit in select patients with omPCa. More importantly, CRP has been consistently shown to improve long-term local symptoms when the tumor progresses across disease states due to resistance to systemic therapies. Metastasis-directed treatments have also emerged as a promising treatment option due to the visibility of oligometastatic disease and new technologies as well as treatment strategies to target the novel PCa colonies. Whether metastases are present at primary cancer diagnosis or detected upon biochemical recurrence after treatment with curative intent, targeted yet decisive elimination of disseminated tumor cell hotspots is thought to improve survival outcomes. One such strategy is salvage lymph node dissection in oligorecurrent PCa which can alter the natural history of progressive PCa. In this review, we will highlight how refinements in modern staging modalities change the classification and treatment of (oligo-)metastatic PCa. Further, we will also discuss the current role and future directions of precision surgery in omPCa.

68Ga-PSMA PET/CT based primary staging and histological correlation after extended pelvic lymph node dissection at radical prostatectomy.

INTRODUCTION: Prostate-specific membrane antigen positron emission tomography-computed tomography (PSMA PET/CT) represents the upcoming standard for the staging of prostate cancer (PCa). However, there is still an unmet need for the validation of PSMA PET/CT at primary staging and consecutive histological correlation. Consequently, we decided to analyze the prediction parameter of PSMA PET/CT at primary staging. METHODS: We relied on 90 ≥ intermediate-risk PCa patients treated with radical prostatectomy (RP) and extended pelvic lymph node dissection. All patients were administered to 68Ga-PSMA PET/CT prior to surgery. 68Ga-PSMA PET/CT data were retrospectively reevaluated by a single radiologist and consequently compared to histological results from RP. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for the detection of lymph node metastases were analyzed per-patient (n = 90), per-pelvic side (n = 180), and per-anatomic-region (external iliac artery and vein left/right vs. obturator fossa left/right vs. internal iliac artery left/right) (n = 458), respectively. RESULTS: Sensitivity, specificity, PPV, and NPV per-patient were: 43.8, 96.0, 70.0, and 88.8%, respectively. Sensitivity, specificity, PPV, and NPV per-pelvic-side were: 42.9, 95.6, 56.3, and 92.7%, respectively. Sensitivity, specificity, PPV, and NPV per-anatomic-region were: 47.6, 98.9, 66.7, and 97.5%, respectively. CONCLUSIONS: Negative 68Ga-PSMA PET/CT results were highly reliable in our study. Positive 68Ga-PSMA PET/CT results, however, revealed less reliable results. Larger and ideally prospective trials are justified to clarify the potential role of PSMA PET/CT based primary staging.

Adherence to Guideline Recommendations for Perioperative Chemotherapy in Patients with pN2-3 M0 Squamous Cell Carcinoma of the Penis: Temporal Trends and Survival Outcomes.

AIMS: To analyse contemporary perioperative chemotherapy (CHT) guideline adherence rates for pN2-3 M0 squamous cell carcinoma of the penis, as well as CHT association with cancer-specific (CSM) and other-cause mortality (OCM). MATERIALS AND METHODS: Within the Surveillance, Epidemiology, and End Results databases, 311 pN2-3 M0 squamous cell carcinoma of the penis patients treated with inguinal lymph node dissection were identified. Univariable and multivariable logistic regression analyses focused on CHT rates, whereas cumulative incidence plots and multivariable competing risks regression analyses tested for CSM and OCM rates. RESULTS: CHT was administered to 140 (45%) patients and rates increased from 37.5 to 62.2% (2004-2015; P = 0.02). Specifically, annual CHT rates increased over time in patients younger or equal to 65 years and in patients older than 65 years (44.4-84.6% versus 28.6-50%, respectively), but this trend was not statistically significant (P = 0.1 and P = 0.2, respectively). The median follow-up was 13 months for both CHT (interquartile range 8.0-32.2) and no-CHT subgroups (interquartile range 5.0-40.0). In multivariable logistic regression analyses, more contemporary year of diagnosis interval (odds ratio 2.08, P < 0.01) and age older than 75 years (odds ratio 0.14, P < 0.001) were independent predictors of CHT use. In multivariable competing risks regression analyses, CHT use did not affect CSM (hazard ratio 1.02; P = 0.7) or OCM (hazard ratio 1.56; P = 0.8). CONCLUSIONS: CHT adherence rates sharply increased in the most recent years. Despite this increase over time, the lack of efficacy regarding CSM benefit is disappointing.

Long-term survival of patients aged 80 years or older treated with radical prostatectomy for prostate cancer.

BACKGROUND: Radical prostatectomy (RP) is the gold standard for clinically localized prostate cancer (PCa) patients with life expectancy (LE) of at least 10 years. We examined long-term survival of men aged 80 years or older treated with RP and we attempted to identify criteria based on age and comorbidities that could predict survival of at least 10 years after RP, to identify those that might be considered for RP. PATIENTS AND METHODS: In Surveillance Epidemiology and End Results (SEER)-Medicare-linked database, we identified 234 octo- and nonagenarians with clinical T1, T2 or T3 PCa treated with RP between 1991 and 2009. Kaplan-Meier analyses examined 10-year survival patterns. Multivariable Cox regression analyses focused on the combined effect of age and/or Charlson Comorbidity Index (CCI) after adjusting for different confounders. RESULTS: The 10-year overall survival (OS) and cancer specific mortality (CSM) rates in the overall population were 51 and 9.9%. In individuals aged 80-81 years old, the 10-year OS was 62.4 vs. 39.6% in older patients (p = 0.001). Moreover, combination of age 80-81 with CCI = 0 yielded 10-year OS of 67.9 vs. 28.5% in older and sicker patients (p < 0.001). Age 80-81, absence of comorbidities and the combination of age 80-81 with CCI = 0, represented independent predictors of lower overall mortality (all p ≤ 0.01). CONCLUSIONS: Two out of three individuals selected for RP aged 80-81 years and without comorbidities, fulfill the criterion of LE of 10 years or more. Therefore, elderly PCa individuals can be suitable for surgical management, if appropriately selected, based on LE criterion.

Prognostic value of the new Grade Groups in Prostate Cancer: a multi-institutional European validation study.

BACKGROUND: We aimed to assess the prognostic relevance of the new Grade Groups in Prostate Cancer (PCa) within a large cohort of European men treated with radical prostatectomy (RP). METHODS: Data from 27 122 patients treated with RP at seven European centers were analyzed. We investigated the prognostic performance of the new Grade Groups (based on Gleason score 3+3, 3+4, 4+3, 8 and 9-10) on biopsy and RP specimen, adjusted for established clinical and pathological characteristics. Multivariable Cox proportional hazards regression models assessed the association of new Grade Groups with biochemical recurrence (BCR). Prognostic accuracies of the models were assessed using Harrell's C-index. RESULTS: Median follow-up was 29 months (interquartile range, 13-54). The 4-year estimated BCR-free survival (bRFS) for biopsy Grade Groups 1-5 were 91.3, 81.6, 69.8, 60.3 and 44.4%, respectively. The 4-year estimated bRFS for RP Grade Groups 1-5 were 96.1%, 86.7%, 67.0%, 63.1% and 41.0%, respectively. Compared with Grade Group 1, all other Grade Groups based both on biopsy and RP specimen were independently associated with a lower bRFS (all P<0.01). Adjusted pairwise comparisons revealed statistically differences between all Grade Groups, except for group 3 and 4 on RP specimen (P=0.10). The discriminations of the multivariable base prognostic models based on the current three-tier and the new five-tier systems were not clinically different (0.3 and 0.9% increase in discrimination for clinical and pathological model). CONCLUSIONS: We validated the independent prognostic value of the new Grade Groups on biopsy and RP specimen from European PCa men. However, it does not improve the accuracies of prognostic models by a clinically significant margin. Nevertheless, this new classification may help physicians and patients estimate disease aggressiveness with a user-friendly, clinically relevant and reproducible method.

Mortality, morbidity and healthcare expenditures after local tumour ablation or partial nephrectomy for T1A kidney cancer.

BACKGROUND: Local tumour ablation (LTA) may yield better perioperative outcomes than partial nephrectomy (PN), however the impact of each treatment on perioperative mortality and health care expenditures is unknown. The aim of the study was to compare mortality, morbidity and health care expenditures between LTA and PN. PATIENTS AND METHODS: A population-based assessment of 2471 patients with cT1a kidney cancer treated with either LTA or PN, between 2000 and 2009, in the SEER-Medicare database was performed. After propensity score matching, 30-day mortality, overall and specific complication rates, length of stay, readmission rates and health care expenditures according to LTA or PN were estimated. Multivariable logistic and linear models addressed the effect of each specific LTA approach on overall complication rates, length of stay, readmission rates and health care expenditures. RESULTS: The 30-day mortality was <2% after either LTA or PN (OR 2.27, p = 0.2). The overall complication rate was 21% after LTA and 40% after PN (OR 0.38, p < 0.001). Blood transfusions, infection/sepsis, wound infections, respiratory complications, gastrointestinal complications, acute kidney injury, and accidental puncture or laceration/foreign body left during procedure rates resulted lower after LTA relative to PN (all p < 0.05). Similarly, length of stay and health care expenditures resulted lower after LTA relative to PN (all p < 0.05). Conversely, readmission rate was not significantly different in LTA relative to PN (p = 0.1). CONCLUSIONS: Despite similar perioperative mortality, LTA is associated with lower complications rate, shorter length of stay and lower health care expenditure relative to PN.

The prognostic role of preoperative serum C-reactive protein in predicting the biochemical recurrence in patients treated with radical prostatectomy.

BACKGROUND: To assess the prognostic value of preoperative C-reactive protein (CRP) serum levels for prognostication of biochemical recurrence (BCR) after radical prostatectomy (RP) in a large multi-institutional cohort. METHODS: Data from 7205 patients treated with RP at five institutions for clinically localized prostate cancer (PCa) were retrospectively analyzed. Preoperative serum levels of CRP within 24 h before surgery were evaluated. A CRP level ⩾0.5 mg dl(-1) was considered elevated. Associations of elevated CRP with BCR were evaluated using univariable and multivariable Cox proportional hazards regression models. Harrel's C-index was used to assess prognostic accuracy (PA). RESULTS: Patients with higher Gleason score on biopsy and RP, extracapsular extension, seminal vesicle invasion, lymph node metastasis, and positive surgical margins status had a significantly elevated preoperative CRP compared to those without these features. Patients with elevated CRP had a lower 5-year BCR survival proportion as compared to those with normal CRP (55% vs 76%, respectively, P<0.0001). In pre- and postoperative multivariable models that adjusted for standard clinical and pathologic features, elevated CRP was independently associated with BCR (P<0.001). However, the addition of preoperative CRP did not improve the accuracy of the standard pre- and postoperative models for prediction of BCR (70.9% vs 71% and 78.9% vs 78.7%, respectively). CONCLUSIONS: Preoperative CRP is elevated in patients with pathological features of aggressive PCa and BCR after RP. While CRP has independent prognostic value, it does not add prognostically or clinically significant information to standard predictors of outcomes.

Adherence of the indication to European Association of Urology guideline recommended pelvic lymph node dissection at a high-volume center: Differences between open and robot-assisted radical prostatectomy.

PURPOSE: Contemporary adherence of the indication to European Association of Urology (EAU) guideline recommendation for pelvic lymph node dissection (PLND) at either open (ORP) or robot-assisted radical prostatectomy (RARP) at a high-volume center is unknown. To assess guideline recommended and observed PLND rates in a high-volume center cohort. METHODS: We relied on the Martini-Clinic database and focused on patients treated with either ORP or RARP, between 2010 and 2013. Actual performed PLND was compared to European Association of Urology (EAU) guideline recommendation defined by nomogram predicted risk of lymph node invasion >5%. Categorical and multivariable logistic regression analyses targeted two endpoints: 1) probability of guideline recommended PLND and 2) probability of no PLND, when not recommended by EAU guideline. RESULTS: Within 7868 PCa patients, adherence to EAU PLND guideline recommendation was 97.1% at ORP and 96.8% at RARP (p = 0.7). When PLND was not recommended, it was more frequently performed at RARP (71.6%) than at ORP (66.2%) (p = 0.002). Gleason score, PSA and number of positive biopsy cores were independent predictors for both either PLND when recommended, or no PLND when not recommended (all p < 0.05). Clinical tumor stage, age and surgical approach were also independent predictors for no PLND when not recommended (all p < 0.05). CONCLUSIONS: Adherence of the indication to EAU guideline recommended PLND is high at this high-volume center. Neither ORP nor RARP represent a barrier for PLND, when recommended. However, a high number of patients underwent PLND despite absence of guideline recommendation. Possible staging advantages and PLND related complications needs to be individually considered, especially, when LNI risk is low.

Differential effect on survival of pelvic lymph node dissection at radical cystectomy for muscle invasive bladder cancer.

PURPOSE: To compare long-term cancer outcomes after radical cystectomy (RC) alone or RC with pelvic lymph node dissection (PLND) according to different age and comorbidities categories. METHODS: Using the SEER-Medicare dataset, 3314 patients diagnosed with urothelial carcinoma of the urinary bladder and treated with RC alone or RC with PLND were identified. After propensity score matching to reduce potential selection bias, all cause mortality (ACM)-free and cancer specific mortality (CSM)-free survival rates were estimated. Multivariable regression models (MVA) addressed the effect of PLND on ACM and CSM. Subgroups analyses according to age and comorbidities were performed. RESULTS: After matching, 688 and 688 patients treated with RC alone or RC with PLND remained. The 5-year ACM-free survival rate was 36 after RC alone and 45% after RC with PLND (p < 0001). In MVA, PLND exerted a protective effect on ACM (HR 0.77, p < 0.001). The 5-year CSM-free survival rate was 54 after RC alone and 65% after RC with PLND (p < 0.001). In MVA, PLND exerted a protective effect on CSM (HR 0.71, p < 0.001). Similar results were observed in younger (age ≤75) and healthier (CCI = 0) patients, where PLND exerted a protective effect on ACM (HR 0.64, p = 0.001) and CSM (HR 0.65, p = 0.01). Conversely, in older (age >75) and sicker (CCI ≥1) patients, PLND was not associated with ACM (HR 0.98, p = 0.8) or CSM (HR 1.01, p = 0.9). CONCLUSIONS: RC with PLND is associated with improved all cause and cancer specific survival in younger and healthier RC candidates but not in older and sicker patients.

Contemporary 90-day mortality rates after radical cystectomy in the elderly.

INTRODUCTION: Existing radical cystectomy (RC) perioperative mortality estimates may underestimate the contemporary rates due to more advanced age, more baseline comorbidities and potentially broader inclusion criteria for RC, relative to past criteria. METHODS: Within the most recent Surveillance, Epidemiology, and End Results (SEER)-Medicare database we identified clinically non-metastatic, muscle-invasive (T2-T4a) urothelial carcinoma of the urinary bladder (UCUB) patients, who underwent RC between 1991 and 2009. Mortality at 30- and 90-day after RC was quantified. Multivariable logistic regression analyses tested predictors of 90-day mortality. RESULTS: Within 5207 assessable RC patients 30- and 90-day mortality rates were 5.2 and 10.6%, respectively. According to age 65-69, 70-79 and ≥ 80 years, 90-day mortality rates were 6.4, 10.1 and 14.8% (p < 0.001). Additionally, 90-day mortality rates increased with increasing Charlson Comorbidity Index (CCI, 0, 1, 2 and ≥ 3): 6.3, 10.3, 12.6 and 15.9% (p < 0.001). 90-day mortality rate in unmarried patients was 13.0 vs. 9.3% in married individuals (p < 0.001). In multivariable logistic regression analyses, advanced age, higher CCI, low socioeconomic status, unmarried status and non organ-confined stage were independent predictors of 90-day mortality (all p < 0.05). CONCLUSIONS: The contemporary SEER-Medicare derived 90-day mortality rates are substantially higher than previously reported estimates from centers of excellence, and even exceed previous SEER reports. More advanced age, higher CCI score, and other patient characteristics that distinguish the current population from others account for these differences.

Clinical nodal staging scores for prostate cancer: a proposal for preoperative risk assessment.

BACKGROUND: Pelvic lymph node dissection in patients undergoing radical prostatectomy for clinically localised prostate cancer is not without morbidity and its therapeutical benefit is still a matter of debate. The objective of this study was to develop a model that allows preoperative determination of the minimum number of lymph nodes needed to be removed at radical prostatectomy to ensure true nodal status. METHODS: We analysed data from 4770 patients treated with radical prostatectomy and pelvic lymph node dissection between 2000 and 2011 from eight academic centres. For external validation of our model, we used data from a cohort of 3595 patients who underwent an anatomically defined extended pelvic lymph node dissection. We estimated the sensitivity of pathological nodal staging using a beta-binomial model and developed a novel clinical (preoperative) nodal staging score (cNSS), which represents the probability that a patient has lymph node metastasis as a function of the number of examined nodes. RESULTS: In the development and validation cohorts, the probability of missing a positive lymph node decreases with increase in the number of nodes examined. A 90% cNSS can be achieved in the development and validation cohorts by examining 1-6 nodes in cT1 and 6-8 nodes in cT2 tumours. With 11 nodes examined, patients in the development and validation cohorts achieved a cNSS of 90% and 80% with cT3 tumours, respectively. CONCLUSIONS: Pelvic lymph node dissection is the only reliable technique to ensure accurate nodal staging in patients treated with radical prostatectomy for clinically localised prostate cancer. The minimum number of examined lymph nodes needed for accurate nodal staging may be predictable, being strongly dependent on prostate cancer characteristics at diagnosis.

The effect of age at diagnosis on prostate cancer mortality: a grade-for-grade and stage-for-stage analysis.

OBJECTIVE: To evaluate the effect of advancing age on cancer-specific mortality (CSM) after radical prostatectomy (RP). MATERIALS AND METHODS: Overall, 205,551 patients with PCa diagnosed between 1988 and 2009 within the Surveillance Epidemiology and End Results (SEER) database were included in the study. Patients were stratified according to age at diagnosis: ≤ 50, 51-60, 61-70, and ≥ 71 years. The 15-year cumulative incidence CSM rates were computed. Competing-risks regression models were performed to test the effect of age on CSM in the entire cohort, and for each grade (Gleason score 2-4, 5-7, and 8-10) and stage (pT2, pT3a, and pT3b) sub-cohorts. RESULTS: Advancing age was associated with higher 15-year CSM rates (2.3 vs. 3.4 vs. 4.6 vs. 6.3% for patients aged ≤ 50 vs. 51-60 vs. 61-70 vs. ≥ 71 years, respectively; P < 0.001). In multivariable analyses, age at diagnosis was a significant predictor of CSM. This relationship was also observed in sub-analyses focusing on patients with Gleason score 5-7, and/or pT2 disease (all P ≤ 0.05). Conversely, age failed to reach the independent predictor status in men with Gleason score 2-4, 8-10, pT3a, and/or pT3b disease. CONCLUSIONS: Advancing age increases the risk of CSM. However, when considering patients affected by more aggressive disease, age was not significantly associated with higher risk of dying from PCa. In high-risk patients, tumor characteristics rather than age should be considered when making treatment decisions.

Association of perioperative blood transfusion with oncologic outcomes after radical nephroureterectomy for upper tract urothelial carcinoma.

BACKGROUND: To test the hypothesis that perioperative blood transfusion (PBT)impacts oncologic outcomes of patients treated with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). METHODS: Retrospective analysis of 2492 patients with UTUC treated at 23 institutions with RNU between 1987 and 2007.Cox regression models addressed the association of PBT with disease recurrence, cancer-specific mortality and any-cause mortality. RESULTS: A total of 510 patients (20.5%) patients received PBT. Within a median follow-up of 36 months (Interquartile range: 55 months), 663 (26.6%) patients experienced disease recurrence, 545 patients (21.9%) died of UTUC and 884 (35.5%) patients died from any cause. Patients who received PBT were at significantly higher risk of disease recurrence, cancer-specific mortality and overall mortality than patients not receiving PBT in univariable Cox regression analyses. In multivariable Cox regression analyses that adjusted for the effects of standard clinicopathologic features, PBT did not remain associated with disease recurrence (HR: 1.11; 95% CI 0.92-1.33, p = 0.25), cancer-specific mortality (HR: 1.09; 95% CI 0.89-1.33, p = 0.41) or overall mortality (HR: 1.09; 95% CI 0.93-1.28, p = 0.29). CONCLUSIONS: In patients undergoing RNU for UTUC, PBT is associated with disease recurrence, cancer-specific survival or overall survival in univariable, but not in multivariable Cox regression analyses.

Intensity-modulated radiation therapy leads to survival benefit only in patients with high-risk prostate cancer: a population-based study.

BACKGROUND: During the last years, there has been a rapid adoption of intensity-modulated radiation therapy (IMRT) in patients with prostate cancer (PCa), despite the lack of randomized trials evaluating its effectiveness. The aim of our study was to evaluate the survival benefit associated with IMRT in patients with PCa. PATIENTS AND METHODS: Overall, 42 483 patients with PCa treated with IMRT or initial observation between 2001 and 2007 within the Surveillance, Epidemiology, and End Results (SEER)-Medicare were evaluated. Patients in both treatment arms were matched using propensity-score methodology. After propensity-score matching, 19 064 patients remained in our analyses. Eight-year cancer-specific mortality (CSM) rates were estimated, and the number needed to treat (NNT) was calculated. Competing risks regression analyses tested the relationship between treatment type and CSM. RESULTS: Overall, the 8-year CSM rates were 3.4% and 4.1% for patients treated with IMRT versus initial observation, respectively (P < 0.001). The corresponding 8-year NNT was 142. In patients with low/intermediate-risk disease, IMRT was not associated with lower CSM rates compared with observation (P = 0.7). In patients with high-risk disease, the 8-year CSM rates for IMRT versus observation were 5.8% versus 10.5%, respectively (P < 0.001). The corresponding NNT was 21. When high-risk patients were stratified according to age (<73 versus ≥73), and Charlson comorbidity index (≤1 versus >1) the 8-year CSM rates for IMRT versus observation were 4.3% versus 9.4% and 6.9% versus 11.9% and 5.3% versus 11.4% and 6.1% versus 10.1%, respectively (all Ps < 0.001). The corresponding NNTs were 19, 21, 16, and 25, respectively. In multivariate analyses, the protective effect of IMRT was more evident in high-risk patients with younger age and lower comorbidities. CONCLUSIONS: IMRT leads to a survival advantage only in patients with high-risk disease. Conversely, patients with low/intermediate-risk disease did not benefit from IMRT at 8-year follow-up.