10-year Prostate Cancer-specific Mortality Research Articles

Impact of Prostate-Specific Antigen Screening Pattern on Prostate Cancer Mortality Among Non-Hispanic Black and Non-Hispanic White Men: A Large, Urban Health System Cohort Analysis.

Randomized studies assessing the effect of PSA screening on mortality in non-Hispanic Black (NHB) men are lacking. We aimed to assess the association between PSA screening and survival among NHB men in comparison to non-Hispanic White (NHW) men in a racially diverse real-world North American population. The study cohort included 6378 men who self-identified as NHB or NHW and were diagnosed with prostate cancer (PCa). Patients received PSA screening and subsequent PCa treatment and follow-up at our institution. Patients were sorted based on PSA testing intensity for the 5 years prior to diagnosis, as follows: never, some (<1 test/y), and annual testing (1 test/y). The primary outcome was risk of prostate cancer-specific mortality (PCSM). Competing risk cumulative incidence curves estimated PCSM rates. Competing risk regression analyses examined the impact of PSA testing on PCSM. An interaction term was incorporated to assess the impact of race on the outcome. Median (IQR) age and PSA at diagnosis were 67 (60-73) years and 5.8 (4.4-9.6) ng/mL, respectively, and 2929 (46%) men were NHB (Kruskal-Wallis P values < .001). Annual PSA testing was more frequent in NHW (5%) than in NHB (3%) men (χ2 P value < .001). On cumulative incidence analysis, in the never, some, and annual PSA testing groups, the 10-year PCSM was respectively 12.3%, 5.8%, and 4.6% in NHW and 18.5%, 7%, and 1.2% in NHB patients (Gray's test P values < .001). At competing risk regression, PSA screening rate was associated with more favorable PCSM rates (HR: 0.47; 95% CI 0.33-0.68; P < .001). The interaction term for race did not show statistical significance (P = .2). PSA testing was associated with a reduced risk of PCSM in both NHB and NHW men diagnosed with PCa. Additionally, the positive impact of the screening rate seemed to be independent of race.

Individual Patient Data Analysis of 17 Randomized Trials vs. Real-World Data for Men with Localized Prostate Cancer Receiving Radiotherapy.

Prior work has demonstrated poor correlation between the results of randomized controlled trials (RCTs) and real-world evidence (RWD). However, patients enrolled in RCTs are often considered to poorly represent the real-world population. Herein, we utilize multiple large data repositories to determine differences in baseline characteristics and long-term outcomes between patients enrolled in RCTs and RWD that received radiotherapy for localized prostate cancer. Meta-Analysis of Randomized trials in Cancer of the Prostate (MARCAP) Consortium was leveraged, and 17 phase III randomized trials were included. RWD were accessed through the Staging Collaboration for Cancer of the Prostate (STAR-CAP) cohort, a cohort that is comprised of >60 centers across the United States and Europe. Additionally, RWD was assessed via the Surveillance, Epidemiology, and End Results (SEER) database. MARCAP and STAR-CAP both contain outcomes for distant metastasis (DM), metastasis-free survival (MFS), prostate cancer-specific mortality (PCSM), and overall survival (OS). SEER only contains PCSM and OS. Wilcoxon signed-rank test and chi-square test were used to compare continuous and categorical variables, respectively. Inverse probability of treatment weighting (IPTW) analysis was conducted, balancing for age, PSA, Gleason score, T stage, and treatment year in the three cohorts. Cox and Fine-Gray regression models were used to compare disease outcomes between RCTs vs. RWD. Data from 10,666 patients from RCTs, 6,530 patients in STAR-CAP, and 117,586 patients in SEER were included. SEER patients were slightly younger (p<0.001, median age 68 (IQR 62-73) than those in RCTs (70, IQR 65-74) and in STAR-CAP (70, IQR 64-74). 10-year OS in RCTs was 65.4%, STAR-CAP 70.2%, SEER 64.1%. OS was superior in STAR-CAP (RCTs as reference; HR 0.91, 95% CI 0.85-0.96, p<0.0001), but there was no significant difference between SEER and RCTs (HR 0.96, 95% CI 0.91-1.02, p = 0.22). 10-year PCSM cumulative incidence was 7.4% in RCTs, 8.1% in STAR-CAP, and 11.0% in SEER. There was no significant difference in PCSM between STAR-CAP RWD and RCTs (HR 0.88, 95% CI 0.78-1.01, p = 0.08), whereas PCSM was worse in SEER than RCTs (HR 1.37, 95% CI 1.21-1.55, p<0.0001). There was no significant difference in DM between STAR-CAP RWD and RCTs (HR 0.93, 95% CI 0.83-1.04, p = 0.2). While baseline differences exist in patients enrolled on localized prostate cancer RCTs and real-world datasets, there were small if any significant relative differences in oncologic outcomes. This provides reassurance that RCT results are generally applicable to patients in routine practice.

Biochemical Recurrence and Risk of Mortality Following Radiotherapy or Radical Prostatectomy

Stratifying patients with biochemical recurrence (BCR) after primary treatment for prostate cancer based on the risk of prostate cancer-specific mortality (PCSM) is essential for determining the need for further testing and treatments. To evaluate the association of BCR after radical prostatectomy or radiotherapy and its current risk stratification with PCSM. This population-based cohort study included a total of 16 311 male patients with 10 364 (64%) undergoing radical prostatectomy and 5947 (36%) undergoing radiotherapy with curative intent (cT1-3, cM0) and PSA follow-up in Stockholm, Sweden, between 2003 and 2019. Follow-up for all patients was until death, emigration, or end of the study (ie, December 31, 2018). Data were analyzed between September 2022 and March 2023. Primary outcomes of the study were the cumulative incidence of BCR and PCSM. Patients with BCR were stratified in low- and high-risk according to European Association of Urology (EAU) criteria. Radical prostatectomy or radiotherapy. A total of 16 311 patients were included. Median (IQR) age was 64 (59-68) years in the radical prostatectomy cohort (10 364 patients) and 69 (64-73) years in the radiotherapy cohort (5947 patients). Median (IQR) follow-up for survivors was 88 (55-138) months and 89 (53-134) months, respectively. Following radical prostatectomy, the 15-year cumulative incidences of BCR were 16% (95% CI, 15%-18%) for the 4024 patients in the low D'Amico risk group, 30% (95% CI, 27%-32%) for the 5239 patients in the intermediate D'Amico risk group, and 46% (95% CI, 42%-51%) for 1101 patients in the high D'Amico risk group. Following radiotherapy, the 15-year cumulative incidences of BCR were 18% (95% CI, 15%-21%) for the 1230 patients in the low-risk group, 24% (95% CI, 21%-26%) for the 2355 patients in the intermediate-risk group, and 36% (95% CI, 33%-39%) for the 2362 patients in the high-risk group. The 10-year cumulative incidences of PCSM after radical prostatectomy were 4% (95% CI, 2%-6%) for the 1101 patients who developed low-risk EAU-BCR and 9% (95% CI, 5%-13%) for 649 patients who developed high-risk EAU-BCR. After radiotherapy, the 10-year PCSM cumulative incidences were 24% (95% CI, 19%-29%) for the 591 patients in the low-risk EAU-BCR category and 46% (95% CI, 40%-51%) for the 600 patients in the high-risk EAU-BCR category. These findings suggest the validity of EAU-BCR stratification system. However, while the risk of dying from prostate cancer in low-risk EAU-BCR after radical prostatectomy was very low, patients who developed low-risk EAU-BCR after radiotherapy had a nonnegligible risk of prostate cancer mortality. Improving risk stratification of patients with BCR is pivotal to guide salvage treatment decisions, reduce overtreatment, and limit the number of staging tests in the event of PSA elevations after primary treatment.

Clinical characteristics and prostate-cancer-specific mortality of competitive risk nomogram in the second primary prostate cancer.

With the development of early diagnosis and treatment, the second primary malignancy (SPM) attracts increasing attention. The second primary prostate cancer (spPCa) is an important class of SPM, but remains poorly understood. We retrospectively analyzed 3,322 patients with spPCa diagnosed between 2004 and 2015 in the Surveillance, Epidemiology, and End Results (SEER) database. Chi-square test was applied to compare demographic and clinical variables and analyze causes of death. Multivariate competitive risk regression model was used to identify risk factors associated with prostate-cancer-specific mortality (PCSM), and these factors were enrolled to build a nomogram of competitive risk. The C-index, calibration curve, and decision curve analysis (DCA) were employed to evaluate the discrimination ability of our nomogram. The median follow-up (interquartile range, IQR) time was 47 (24-75) months, and the median (IQR) diagnosis interval between the first primary cancer (FPC) and spPCa was 32 (16-57) months. We found that the three most common sites of SPM were the urinary system, digestive system, and skin. Through multivariate competitive risk analysis, we enrolled race (p < 0.05), tumor-node-metastasis (TNM) stage (p < 0.001), Gleason score (p < 0.05), surgery (p = 0.002), and radiotherapy (p = 0.032) to construct the model to predict the outcomes of spPCa. The C-index was 0.856 (95% CI, 0.813-0.899) and 0.905 (95% CI, 0.941-0.868) in the training and validation set, respectively. Moreover, both the calibration curve and DCA illustrated that our nomogram performed well in predicting PCSM. In conclusion, we identified four risk factors associated with the prognosis of spPCa and construct a competing risk nomogram, which performed well in predicting the 3-, 5-, and 10-year PCSM.

Patient-level data meta-analysis of a multi-modal artificial intelligence (MMAI) prognostic biomarker in high-risk prostate cancer: Results from six NRG/RTOG phase III randomized trials.

299 Background: Recently, an MMAI prognostic biomarker, ArteraAI Prostate, was trained and validated in localized prostate cancer to more accurately risk stratify patients for multiple endpoints compared to NCCN risk groups (Esteva et al., 2022). Prognostication within an NCCN risk group remains clinically important given the multiple treatment decisions required within each risk group (e.g., radiotherapy dose or hormone therapy use). Herein, we validated the MMAI biomarker in high-risk prostate cancer where an increasing number of therapeutic decisions is required. Methods: This study leveraged histopathology image and clinical data from patients with at least one high-risk feature (HRF; cT3-cT4, Gleason 8-10, PSA &gt; 20 ng/mL, primary Gleason pattern 5) from six NRG/RTOG phase III randomized trials (n=1,088). Patients from two trials not part of the initial MMAI biomarker training/validation (RTOG 0521 [n=344] and 9902 [n=318]) and the MMAI validation cohort (RTOG 9202, 9408, 9413, and 9910 [n=426]) were included. Fine-Gray, cumulative incidence, and time dependent area under the curve (tdAUC) analyses were performed for time to distant metastasis (DM) and prostate cancer-specific mortality (PCSM) for standard clinicopathologic variables (age, PSA, Gleason score, T-stage, number of HRFs) and the MMAI model, as a continuous score (per standard deviation increase) and categorically by quartile. Death from other causes were treated as competing risks. Results: The analyzed cohort had a median follow-up of 10.4 years. Median PSA was 21 ng/mL, 60% had Gleason 8-10 disease, 37% had cT3-T4 disease, and 20% were African American. On univariable analysis, the MMAI model was significantly associated with DM (subdistribution hazard ratio [sHR] 2.05, 95% CI 1.74-2.43, p&lt;0.001) and PCSM (sHR 2.04, 95% CI 1.73-2.42, &lt;0.001). On multivariable analysis, the MMAI model, adjusting for either age, PSA, Gleason score, T-stage, or number of HRFs, was the only variable significantly associated with DM. TdAUC was highest for the MMAI biomarker for both 5-year DM (0.71), compared to PSA (0.56), Gleason score (0.61), T-stage (0.63), or number of HRFs (0.64), and for 5-year PCSM (0.75), compared to clinicopathologic variables (range 0.53-0.63). The estimated 10-year DM and 15-year PCSM rates for MMAI quartile 1 vs 4 were 8% vs 31% and 8% vs 34%, respectively. Conclusions: Our novel MMAI prognostic biomarker was successfully validated across six phase III randomized trials with long-term follow-up to be independently prognostic over standard clinical and pathologic variables for men with high-risk prostate cancer. Despite all patients having high-risk disease, the MMAI biomarker identified those with highly variable risks for DM and PCSM. This tool can help enable personalized, shared decision making for patients and providers.

This Month in Adult Urology

This Month in Adult Urology

A Nationwide Analysis of Risk of Prostate Cancer Diagnosis and Mortality following an Initial Negative Transrectal Ultrasound Biopsy with Long-Term Followup.

Magnetic resonance imaging (MRI) targeted prostate biopsy has been shown to find many high-grade prostate cancers in men with concurrent negative transrectal ultrasound (TRUS) systematic biopsy. The oncologic risk of such tumors can be explored by looking at long-term outcomes of men with negative TRUS biopsy followed without MRI. The aim was to analyze the mortality after initial and second negative TRUS biopsy. All men who underwent initial TRUS biopsies between January 1, 1995 and December 31, 2016 in Denmark were included. A total of 37,214 men had a negative initial TRUS biopsy and 6,389 underwent a re-biopsy. Risk of cause-specific mortality was analyzed with competing risks. Diagnosis of Gleason score ≥7 prostate cancer following negative biopsies was analyzed with multivariable logistic regression including time to re-biopsy, prostate specific antigen (PSA), age and digital rectal examination. The 15-year prostate cancer-specific mortality was 1.9% (95% CI: 1.7-2.1). Prostate cancer-specific mortality was 1.3% (95% CI: 0.9-1.6) and 4.6% (95% CI: 3.4-5.8) for men with PSA <10 and >20 ng/ml, respectively. Of the TRUS re-biopsies 12% were Gleason score ≥7 and risk of Gleason score ≥7 increased with longer time to re-biopsy (p <0.001). Mortality after re-biopsy was similar to after initial biopsy. Men with negative TRUS biopsies have a very low prostate cancer-specific mortality, especially with PSA <10 ng/ml. This raises serious questions about the routine use of MRI targeting for initial prostate biopsy and suggests that MRI targeting should only be recommended for men with PSA >10 ng/ml after negative biopsy.

Prognostic Significance of the Risk of Non-localized Disease on PSMA/PET: Comparative Performance of a Novel, PSMA/PET-Derived Risk Stratification Tool for High-Risk Prostate Cancer in a Large, Multi-Institutional Cohort

<h3>Purpose/Objective(s)</h3> Occult non-localized disease (N1 or M1) at the time of definitive treatment of high-risk prostate cancer (HR-PCa) underlies most treatment failures. We recently developed a nomogram tuned to the identification of non-localized disease on prostate specific membrane antigen PET/CT (PSMA PET/CT) in patients with cN0M0 HR-PCa by conventional imaging, which incorporates iPSA, percent positive core on biopsy, Gleason Grade and cT stage. We systematically compared the prognostic performance of the PSMA nomogram against other validated risk stratification tools for HR-PCa. <h3>Materials/Methods</h3> We identified 5275 men from a multi-institutional database treated with radical prostatectomy (55%), external beam radiation therapy (EBRT, 31%), or EBRT and brachytherapy (14%). The prognostic performance of the PSMA nomogram was compared against the STAR-CAP score, the Cancer of the Prostate Risk Assessment (CAPRA) score, Cambridge Prognostic Groups (CPG) risk group, and Memorial Sloan Kettering Cancer Center (MSKCC) nomogram of 5-year recurrence probability. Accuracy was determined for 5- and 10-year distant metastasis (DM) and prostate cancer specific mortality (PCSM) using the concordance index (C-index). <h3>Results</h3> Median follow-up was 50.3 months (interquartile range 28.1-84.5 months). Overall, 16.1% developed DM, and 4.6% died from PCa. C-indices for the PSMA nomogram were 0.67 and 0.67 for 5- and 10-year DM, and 0.69 and 0.73 for 5- and 10-year PCSM, respectively. The PSMA nomogram outperformed CAPRA, CPG, and MSKCC for all endpoints, outperformed STAR-CAP for 10-year DM, and performed similarly to STAR-CAP for all other endpoints (see Table). The comparative performance between the tools was generally maintained at different follow-up times and in subgroup analyses stratified by primary treatment modalities. <h3>Conclusion</h3> A nomogram tuned to the detection of non-localized disease on PSMA/PET in HR-PCa patients is significantly prognostic of important clinical endpoints, with performance comparable to STAR-CAP and superior to other tools. These data strongly suggest that upstaging based on PSMA PET/CT provides clinically relevant information and warrant prospective validation.

PD08-09 META-ANALYSIS OF RADIATION THERAPY AND ANDROGEN DEPRIVATION THERAPY IN LOCALIZED PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Localized: Radiation Therapy (PD08)1 Sep 2021PD08-09 META-ANALYSIS OF RADIATION THERAPY AND ANDROGEN DEPRIVATION THERAPY IN LOCALIZED PROSTATE CANCER Tommy Jiang, Daniela Markovic, Jay Patel, Jesus Juarez, Martin Ma, David Shabsovich, Nicholas Zaorsky, Nicholas Nickols, Robert Reiter, David Elashoff, Matthew Rettig, Daniel Spratt, and Amar Kishan Tommy JiangTommy Jiang More articles by this author , Daniela MarkovicDaniela Markovic More articles by this author , Jay PatelJay Patel More articles by this author , Jesus JuarezJesus Juarez More articles by this author , Martin MaMartin Ma More articles by this author , David ShabsovichDavid Shabsovich More articles by this author , Nicholas ZaorskyNicholas Zaorsky More articles by this author , Nicholas NickolsNicholas Nickols More articles by this author , Robert ReiterRobert Reiter More articles by this author , David ElashoffDavid Elashoff More articles by this author , Matthew RettigMatthew Rettig More articles by this author , Daniel SprattDaniel Spratt More articles by this author , and Amar KishanAmar Kishan More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001976.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Dose escalation of radiation therapy (RT) and the addition or prolongation of androgen deprivation therapy (ADT) have been independently shown to improve long-term outcomes in randomized trials for localized prostate cancer (PCa). We sought to explore the relative benefits of RT dose intensification and concomitant ADT compared to each other as well as to the historical standard of low dose RT. METHODS: PubMed was searched for Phase III randomized, controlled trials using RT for localized PCa following PRISMA guidelines. Selected trial arms were categorized as low or high dose as well as with or without ADT (categorized as short or long-term). 74 Gy was used as the threshold for “high dose” and 8 months of ADT therapy was the threshold for long-term ADT (LTADT). Outcomes included 5-year overall survival (OS), 5-year prostate cancer specific mortality (PCSM), and 5-year incidence of distant metastases (DM). Pairwise comparisons between treatments were performed using random effects meta regression models with a Bonferroni correction, where the null hypothesis was rejected for p <0.006 with respect to OS and PCSM (9 pairwise comparisons for each) and p <0.008 with respect to DM (6 pairwise comparisons). RESULTS: Forty trials recruiting a total of 21,429 patients met our inclusion criteria. Comparisons of each treatment type are shown in Table 1. Of note, when using low dose RT as the reference, low Dose RT + LTADT showed statistical improvement in PCSM (OR: 0.34 [0.22-0.54]), and DM (OR: 0.35 [0.20-0.63]). Dose escalation alone showed no statistical improvement in any reported outcome compared to low dose RT alone. When compared together, low Dose RT + LTADT was associated with improved 5-yr PCSM (OR: 0.40 [0.25-0.64]) when compared to high Dose RT alone. Improvement in OS and DM did not reach statistical significance. Overall, there was no statistical improvement in 5-year OS comparing any of the treatment modalities. CONCLUSIONS: The results of this meta-analysis suggest the benefit of adding any ADT (STADT or LTADT) to low dose RT alone outweighs the benefits of solely intensifying radiation dose. Dose escalation alone did not demonstrate any significant improvement in OS, PCSM, or DM and appeared to be associated with worse outcomes when compared to low dose RT + LTADT. Source of Funding: N/A © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e117-e117 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Tommy Jiang More articles by this author Daniela Markovic More articles by this author Jay Patel More articles by this author Jesus Juarez More articles by this author Martin Ma More articles by this author David Shabsovich More articles by this author Nicholas Zaorsky More articles by this author Nicholas Nickols More articles by this author Robert Reiter More articles by this author David Elashoff More articles by this author Matthew Rettig More articles by this author Daniel Spratt More articles by this author Amar Kishan More articles by this author Expand All Advertisement Loading ...

Radiation therapy dose and androgen deprivation therapy in localized prostate cancer: a meta-regression of 5-year outcomes in phase III randomized controlled trials

BackgroundWhile multiple randomized trials have evaluated the benefit of radiation therapy (RT) dose escalation and the use and prolongation of androgen deprivation therapy (ADT) in the treatment of prostate cancer, few studies have evaluated the relative benefit of either form of treatment intensification with each other. Many trials have included treatment strategies that incorporate either high or low dose RT, or short-term or long-term ADT (STADT or LTADT), in one or more trial arms. We sought to compare different forms of treatment intensification of RT in the context of localized prostate cancer.MethodsUsing preferred reporting items for systemic reviews and meta-analyses (PRISMA) guidelines, we collected over 40 phases III clinical trials comparing different forms of RT for localized prostate cancer. We performed a meta-regression of 40 individual trials with 21,429 total patients to allow a comparison of the rates and cumulative proportions of 5-year overall survival (OS), prostate cancer-specific mortality (PCSM), and distant metastasis (DM) for each treatment arm of every trial.ResultsDose-escalation either in the absence or presence of STADT failed to significantly improve any 5-year outcome. In contrast, adding LTADT to low dose RT significantly improved 5-year PCSM (Odds ratio [OR] 0.34, 95% confidence interval [CI] 0.22–0.54, p < 0.001) and DM (OR 0.35, 95% CI 0.20–0.63. p < 0.001) over low dose RT alone. Adding STADT also significantly improved 5-year PCSM over low dose RT alone (OR 0.55, 95% CI 0.41–0.75, p < 0.001).ConclusionWhile limited by between-study heterogeneity and a lack of individual patient data, this meta-analysis suggests that adding ADT, versus increasing RT dose alone, offers a more consistent improvement in clinical endpoints.

Application of a novel machine learning framework for predicting non-metastatic prostate cancer-specific mortality in men using the Surveillance, Epidemiology, and End Results (SEER) database

Accurate prognostication is crucial in treatment decisions made for men diagnosed with non-metastatic prostate cancer. Current models rely on prespecified variables, which limits their performance. We aimed to investigate a novel machine learning approach to develop an improved prognostic model for predicting 10-year prostate cancer-specific mortality and compare its performance with existing validated models. We derived and tested a machine learning-based model using Survival Quilts, an algorithm that automatically selects and tunes ensembles of survival models using clinicopathological variables. Our study involved a US population-based cohort of 171 942 men diagnosed with non-metastatic prostate cancer between Jan 1, 2000, and Dec 31, 2016, from the prospectively maintained Surveillance, Epidemiology, and End Results (SEER) Program. The primary outcome was prediction of 10-year prostate cancer-specific mortality. Model discrimination was assessed using the concordance index (c-index), and calibration was assessed using Brier scores. The Survival Quilts model was compared with nine other prognostic models in clinical use, and decision curve analysis was done. 647 151 men with prostate cancer were enrolled into the SEER database, of whom 171 942 were included in this study. Discrimination improved with greater granularity, and multivariable models outperformed tier-based models. The Survival Quilts model showed good discrimination (c-index 0·829, 95% CI 0·820-0·838) for 10-year prostate cancer-specific mortality, which was similar to the top-ranked multivariable models: PREDICT Prostate (0·820, 0·811-0·829) and Memorial Sloan Kettering Cancer Center (MSKCC) nomogram (0·787, 0·776-0·798). All three multivariable models showed good calibration with low Brier scores (Survival Quilts 0·036, 95% CI 0·035-0·037; PREDICT Prostate 0·036, 0·035-0·037; MSKCC 0·037, 0·035-0·039). Of the tier-based systems, the Cancer of the Prostate Risk Assessment model (c-index 0·782, 95% CI 0·771-0·793) and Cambridge Prognostic Groups model (0·779, 0·767-0·791) showed higher discrimination for predicting 10-year prostate cancer-specific mortality. c-indices for models from the National Comprehensive Cancer Care Network, Genitourinary Radiation Oncologists of Canada, American Urological Association, European Association of Urology, and National Institute for Health and Care Excellence ranged from 0·711 (0·701-0·721) to 0·761 (0·750-0·772). Discrimination for the Survival Quilts model was maintained when stratified by age and ethnicity. Decision curve analysis showed an incremental net benefit from the Survival Quilts model compared with the MSKCC and PREDICT Prostate models currently used in practice. A novel machine learning-based approach produced a prognostic model, Survival Quilts, with discrimination for 10-year prostate cancer-specific mortality similar to the top-ranked prognostic models, using only standard clinicopathological variables. Future integration of additional data will likely improve model performance and accuracy for personalised prognostics. None.

Prostate cancer-specific mortality burden by risk group among men with localized disease: Implications for research and clinical trial priorities.

To estimate contemporary population-based patterns of the relative burden of prostate cancer-specific mortality (PCSM) attributable to each N0M0 prostate cancer risk-group, that may guide prioritization in research, trial design, and clinical practice. We categorized 2004-2015 Surveillance, Epidemiology, and End Results database patients by risk group (low, favorable intermediate, unfavorable intermediate, high, and very highrisk). Using the Fine-Gray method, we calculated the relative burden of 10-year PCSM attributable to each risk group. Among N = 337 162 men (6.8-year median follow-up; median age 65 years), the relative proportion of low-, favorable intermediate-, unfavorable intermediate-, high-, and very high-risk diagnoses were 29.9% (N = 100 969), 31.1% (N = 104 696), 17.9% (N = 60 360), 18.1% (N = 61 023), and 3.0% (N = 10 114). Within 10 years of diagnosis, among patients who died of prostate cancer (N = 15 064), 5.0% (N = 746) had low-risk, 13.7% (N = 2060) had favorable intermediate-risk, 16.1% (N = 2429) had unfavorable intermediate-risk, 47.8% (N = 7196) had high-risk, and 17.5% (N = 2633) had very high-risk disease at diagnosis. Patients aged 65 and older accounted for 51.9% of all diagnoses and 72.3% of 10-year PCSM. Although black patients accounted for 15.0% of low-risk diagnoses, they accounted for 20.6% of 10-year PCSM. White patients accounted for 80.3% of low-risk diagnoses and 75.7% of 10-year PCSM. Although high-risk and very high-risk disease account for one-fifth of diagnoses, they account for two-thirds of 10-year PCSM. Older patients and black patients with low-risk disease accounted for a disproportionately large proportion of deaths. These findings support targeting research toward high-risk disease and ensuring adequate representation of older and black men in clinical trials.

Comparative performance and external validation of the multivariable PREDICT Prostate tool for non-metastatic prostate cancer: a study in 69,206 men from Prostate Cancer data Base Sweden (PCBaSe)

BackgroundPREDICT Prostate is an endorsed prognostic model that provides individualised long-term prostate cancer-specific and overall survival estimates. The model, derived from UK data, estimates potential treatment benefit on overall survival. In this study, we externally validated the model in a large independent dataset and compared performance to existing models and within treatment groups.MethodsMen with non-metastatic prostate cancer and prostate-specific antigen (PSA) < 100 ng/ml diagnosed between 2000 and 2010 in the nationwide population-based Prostate Cancer data Base Sweden (PCBaSe) were included. Data on age, PSA, clinical stage, grade group, biopsy involvement, primary treatment and comorbidity were retrieved. Sixty-nine thousand two hundred six men were included with 13.9 years of median follow-up. Fifteen-year survival estimates were calculated using PREDICT Prostate for prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM). Discrimination was assessed using Harrell’s concordance (c)-index in R. Calibration was evaluated using cumulative available follow-up in Stata (TX, USA).ResultsOverall discrimination of PREDICT Prostate was good with c-indices of 0.85 (95% CI 0.85–0.86) for PCSM and 0.79 (95% CI 0.79–0.80) for ACM. Overall calibration of the model was excellent with 25,925 deaths predicted and 25,849 deaths observed. Within the conservative management and radical treatment groups, c-indices for 15-year PCSM were 0.81 and 0.78, respectively. Calibration also remained good within treatment groups. The discrimination of PREDICT Prostate significantly outperformed the EAU, NCCN and CAPRA scores for both PCSM and ACM within this cohort overall.A key limitation is the use of retrospective cohort data.ConclusionsThis large external validation demonstrates that PREDICT Prostate is a robust and generalisable model to aid clinical decision-making.

Cryosurgery Versus Primary Androgen Deprivation Therapy for Locally Recurrent Prostate Cancer After Primary Radiotherapy: A Propensity-Matched Survival Analysis.

BackgroundOptimal management of isolated local recurrence of prostate cancer after primary radiotherapy remains to be defined. Up-front androgen deprivation therapy (ADT) is widely used but may adversely affect the quality of life and is essentially a palliative treatment. Local salvage carries a different side-effect profile and is potentially curative, but it has not been compared to ADT.Materials and methodsWe conducted a propensity-matched analysis of cohorts of men treated with either whole gland cryotherapy (CRYO) or primary ADT following the diagnosis of locally recurrent prostate cancer. Our specific objectives were to compare overall survival (OS) and prostate cancer-specific mortality (PCSM) between CRYO vs. ADT.ResultsAfter a one-to-one matching, 169 patients from each cohort were included in comparisons. Median follow-up time was 6.7 years (ADT) vs. 18 years (CRYO). The 10-year PCSM was 18.5% (ADT) vs. 16.2% (CRYO), which was not statistically different [hazard ratioo (HR): 0.69, 95% CI: 0.36-1.34, p=0.27]. The median OS was 12.3 years (CRYO) versus 10.2 years (ADT) (HR: 0.63, 95% CI: 0.42-0.95, p=0.03).ConclusionsWhile PCSM was similar between the two strategies, CRYO was associated with a longer OS compared to primary ADT. Given the retrospective nature of the trial, these results should be considered hypothesis-generating, and phase III trials comparing these two options are required to further explore these findings.

Competing Risks of Mortality among Men with Biochemical Recurrence after Radical Prostatectomy.

Men with biochemical recurrence after radical prostatectomy need information on competing risks of mortality to inform prognosis and guide treatment. We quantified the risk of prostate cancer metastasis and mortality, and other cause mortality across key clinical predictors. We analyzed 1,225 men with biochemical recurrence after radical prostatectomy from 2001 to 2017 in the VA SEARCH database. Multivariable competing risks regression was used to identify predictors and quantify cumulative incidence of metastasis, prostate cancer specific mortality and other cause mortality. Recursive partitioning analysis was used to identify optimum variable cut points for prediction of prostate cancer specific mortality and other cause mortality. During a median followup of 5.6 years after biochemical recurrence (IQR 2.7-9.1), 243 (20%) men died of other causes and 68 (6%) died of prostate cancer. Multivariable competing risks regression showed that high D'Amico tumor risk and prostate specific antigen doubling time at biochemical recurrence less than 9 months were associated with metastasis and prostate cancer specific mortality (p ≤0.001). Ten-year prostate cancer specific mortality was 14% and 9% for those with high risk tumors and prostate specific antigen doubling time less than 9 months, respectively. Advanced age and worse comorbidity were associated with other cause mortality (p ≤0.001). Ten-year other cause mortality was higher among men 70 years old or older with any Charlson comorbidity (1-3+) (40% to 49%) compared to those with none (20%). Recursive partitioning analysis identified optimal variable cut points for prediction of prostate cancer specific mortality and other cause mortality, with 10-year prostate cancer specific mortality ranging from 3% to 59% and 10-year other cause mortality ranging from 17% to 50% across risk subgroups. Among men with biochemical recurrence after radical prostatectomy, there is significant heterogeneity in prognosis that can be explained by available clinical variables. Men in their 70s with any major comorbidity are 2 to 10 times more likely to die of other causes than of prostate cancer.

MP53-10 SURGICAL MANAGEMENT VERSUS COMBINATION RADIOTHERAPY IN GLEASON SCORE 9-10 PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Localized: Radiation Therapy (MP53)1 Apr 2020MP53-10 SURGICAL MANAGEMENT VERSUS COMBINATION RADIOTHERAPY IN GLEASON SCORE 9-10 PROSTATE CANCER Edward Dee*, Martin King, Santino Butler, Zizi Yu, Sybil Sha, David Yang, Brandon Mahal, Kent Mouw, Anthony D'Amico, Paul Nguyen, and Vinayak Muralidhar Edward Dee*Edward Dee* More articles by this author , Martin KingMartin King More articles by this author , Santino ButlerSantino Butler More articles by this author , Zizi YuZizi Yu More articles by this author , Sybil ShaSybil Sha More articles by this author , David YangDavid Yang More articles by this author , Brandon MahalBrandon Mahal More articles by this author , Kent MouwKent Mouw More articles by this author , Anthony D'AmicoAnthony D'Amico More articles by this author , Paul NguyenPaul Nguyen More articles by this author , and Vinayak MuralidharVinayak Muralidhar More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000915.010AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: For men with Gleason score 9-10 prostate cancer, studies have demonstrated conflicting results on the outcomes from combination radiation therapy (ComboRT) with external beam radiation therapy plus brachytherapy boost versus radical prostatectomy (RP), with or without adjuvant radiation therapy (ART). Differences in patient selection and management may explain some of the disparate outcomes of prior reports. METHODS: The Surveillance, Epidemiology, and End Results database identified 10,396 men managed with ComboRT versus RP (+/-ART). Competing-risks regression analysis with treatment propensity adjustment defined hazard ratios (aHR) for prostate cancer-specific mortality (PCSM), controlling for patient-specific demographic factors. To explore the possible effect of patient selection, analyses were conducted before and after excluding men from analysis if they had evidence-based indications for ART (adverse pathology, i.e. pT3-T4 or positive margins) but did not receive it. RESULTS: Median age was 64 years; median follow-up was 69 months. Five-year PCSM was similar between patients treated with RP (with or without ART, regardless of pathologic features, N=8,934) and ComboRT (N=1,462) (6.9% vs 8.1%, aHR=0.94, 95% confidence interval [CI] 0.78–1.13, P=0.51). After excluding RP-treated men with adverse pathology who did not receive ART (N=4,527 excluded), patients treated with RP+/-ART (N=4,407) had improved 5-year PCSM compared with those treated with ComboRT (5.3% vs 8.1%, aHR=0.74, 95% CI 0.60–0.91, P=0.004). CONCLUSIONS: For Gleason 9-10 prostate cancer, ComboRT was associated with similar PCSM compared to RP, but risk-tailored surgical management may be associated with superior PCSM. Source of Funding: No funding. © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e786-e786 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Edward Dee* More articles by this author Martin King More articles by this author Santino Butler More articles by this author Zizi Yu More articles by this author Sybil Sha More articles by this author David Yang More articles by this author Brandon Mahal More articles by this author Kent Mouw More articles by this author Anthony D'Amico More articles by this author Paul Nguyen More articles by this author Vinayak Muralidhar More articles by this author Expand All Advertisement PDF downloadLoading ...

Surgical management versus combination radiotherapy in Gleason score 9-10 prostate cancer.

135 Background: For men with Gleason score 9-10 prostate cancer, studies have demonstrated conflicting results on the outcomes from combination radiation therapy (ComboRT) with external beam radiation therapy plus brachytherapy boost versus radical prostatectomy (RP), with or without adjuvant radiation therapy (ART). Differences in patient selection and management may explain some of the disparate outcomes of prior reports. Methods: The Surveillance, Epidemiology, and End Results database identified 10,396 men managed with ComboRT versus RP (+/-ART). Competing-risks regression analysis with treatment propensity adjustment defined hazard ratios (aHR) for prostate cancer-specific mortality (PCSM), controlling for patient-specific demographic factors. To explore the possible effect of patient selection, analyses were conducted before and after excluding men from analysis if they had evidence-based indications for ART (adverse pathology, i.e. pT3-T4 or positive margins) but did not receive it. Results: Median age was 64 years; median follow-up was 69 months. Five-year PCSM was similar between patients treated with RP (with or without ART, regardless of pathologic features, N=8,934) and ComboRT (N=1,462) (6.9% vs 8.1%, aHR=0.94, 95% confidence interval [CI] 0.78–1.13, P=0.51). After excluding RP-treated men with adverse pathology who did not receive ART (N=4,527 excluded), patients treated with RP+/-ART (N=4,407) had improved 5-year PCSM compared with those treated with ComboRT (5.3% vs 8.1%, aHR=0.74, 95% CI 0.60–0.91, P=0.004). Conclusions: For Gleason 9-10 prostate cancer, ComboRT was associated with similar PCSM compared to RP, but risk-tailored surgical management may be associated with superior PCSM.

Combined External Beam Radiation Therapy and Brachytherapy versus Radical Prostatectomy with Adjuvant Radiation Therapy for Gleason 9-10 Prostate Cancer.

It remains controversial whether external beam radiation therapy with a brachytherapy boost provides oncologic outcomes equivalent to those of radical prostatectomy with or without adjuvant radiation therapy in men with Gleason 9-10 prostate cancer. We compared external beam radiation therapy plus brachytherapy to radical prostatectomy plus adjuvant radiation therapy for Gleason 9-10 prostate cancer in terms of overall survival and prostate cancer specific mortality in 2 large national databases. Using the NCDB (National Cancer Database) and the SEER (Surveillance, Epidemiology, and End Results) database, we identified 4,367 and 2,276 patients, respectively, diagnosed with clinical T1-T3N0M0, Gleason 9-10, prostate specific antigen 0 to 40 ng/ml prostate cancer treated with external beam radiation therapy plus brachytherapy or radical prostatectomy plus adjuvant radiation therapy. We compared overall survival and prostate cancer specific mortality using inverse probability of treatment weighted multivariable Cox proportional hazards regression modeling after accounting for clinical and demographic factors. Median followup in the NCDB and SEER cohorts was 6.0 years and 5.8 years, respectively. In the NCDB cohort there was no significant difference in 5-year overall survival between radical prostatectomy plus adjuvant radiation therapy vs external beam radiation therapy plus brachytherapy (86.7% vs 87.0%, AHR 1.10, 95% CI 0.95-1.27, p=0.220). Results were unchanged when including only patients who received androgen deprivation therapy. In the SEER cohort there was no difference in 5-year prostate cancer specific mortality (6.0% vs 5.7%, AHR 1.22, 95% CI 0.0.88-1.71, p=0.234). There was no significant interaction between patient age (65 years or greater vs less than 65) and treatment modality in the NCDB or SEER cohorts. In men with Gleason 9-10 prostate cancer multimodality surgical therapy is equivalent to external beam radiation therapy plus brachytherapy.

Development and Validation of the First AJCC Compliant Clinical Staging System for Localized Prostate Cancer: Results from a Multicenter International Study

The American Joint Committee on Cancer (AJCC) Precision Medicine Core recently established criteria to evaluate prediction models for incorporation into staging. All previously developed models for localized prostate cancer were excluded from the AJCC 8th edition, primarily because endpoints other than survival were used, and staging was devised through expert opinion. We therefore sought to develop the first AJCC compliant staging system for use in localized prostate cancer. Eligible patients had T1-4N0-1M0 prostate cancer treated between 1992-2013 with radical prostatectomy (RP) or radiotherapy (either external beam (EBRT) and/or brachytherapy with or without androgen deprivation therapy (ADT)). Over 50 centers provided data, including centers in the USA, Canada, and Europe, and across academic, community, and Veterans Affairs medical centers. Patients with M1 disease or PSA>200 ng/ml, and those with preoperative ADT were excluded. The final cohort was randomly split into training and validation sets. An a priori statistical plan was utilized, and statisticians were blinded to the validation cohort until a locked training model was developed. The primary endpoint was prostate cancer-specific mortality (PCSM) treating non-cancer death as a competing-risk. Model discrimination (C-index), calibration, and overall performance (Integrated Brier Score R-squared (IBSR2)) were assessed at 3-, 5-, 10- and 15-years with 10-year results reported below. A total 19,684 men were included, of which 12,421 were treated with RP, 5942 with EBRT, and 1321 with brachytherapy (+/-EBRT). Median follow-up was 72 months (range, 1-289 months), and 4078 were followed for at least 10 years. Novel cut points and groupings were identified that are not currently used in existing prognostic systems, including age, PSA, and percent positive cores. In the new score model, nine tiers were identified (Stage Ia-c, IIa-c, and IIIa-c), and predicted 10-year PCSM ranged from 0.3% to 40%. In the validation set, 10-year discrimination for the new system (C-index 0.796) were superior to the AJCC 8th edition (0.757); overall performance (IBSR2 0.048) was also improved over AJCC 8th edition (IBSR2 0.035). The new staging system was also superior to AJCC 8th edition across primary treatment modality (surgery, EBRT, brachytherapy), age, and race. Using a large, diverse international cohort treated with standard curative treatment options with long term follow up, we have developed and validated the first AJCC compliant clinical staging system for prostate cancer that is superior in each metric to the current AJCC 8th edition and is ready for AJCC committee evaluation.

Comparative effectiveness of treatments for high-risk prostate cancer patients

BackgroundTo determine the comparative effectiveness of primary radical prostatectomy (RP) compared to external bean radiation therapy (EBRT) with androgen deprivation therapy (ADT), or EBRT plus brachytherapy (BT) with or without ADT among Medicare fee-for-service beneficiaries with high-risk prostate cancer, for 10-year, mortality (overall and prostate cancer-specific), complications, health service use, and cost. MethodsThis population-based cohort study used Surveillance, Epidemiology, and End Results – Medicare data. Eligible patients were men aged 66 or older and diagnosed with high-risk prostate cancer between 1996 and 2003. Outcomes evaluated were 10-year overall mortality and prostate cancer-specific mortality, complications, health service use, and cost. We used Cox regression, Poisson regression, and Generalized Linear Model (GLM) log-link models to assess the outcomes. Main findingsThe 10-year overall mortality of EBRT + ADT was comparable to that of the RP group (hazard ratio [HR] = 1.09, confidence interval [CI] = 0.72–1.66). The EBRT + BT ± ADT group had overall survival advantage compared to RP (HR = 0.47, CI = 0.31–0.73). Compared to the RP group, EBRT + ADT group had higher 10-year prostate cancer-specific mortality (HR = 2.19, CI = 1.92–5.21). Both EBRT + ADT and EBRT + BT ± ADT were associated with higher 10-year cost (odds ratio = 1.72, CI = 1.35–2.20; and odds ratio = 1.63, CI = 1.29–2.04), compared to RP group. Complications and health service use varied across 3 treatment groups and across phases of care. Principal conclusionsOur results also demonstrate long-term overall survival benefits for EBRT + BT ± ADT, and greater bowel and bladder side effects over a decade, compared to RP. The RP group had advantage for long-term prostate-cancer specific mortality, compared to EBRT + ADT group. Thus, RP can provide superior cancer control with clear cost advantage for older men with high-risk disease. In terms of value proposition, our results support RP as preferred treatment option, compared to EBRT + ADT and EBRT + BT ± ADT for high-risk prostate cancer patients.