Introduction Bayesian statistics provide direct probabilistic interpretations that align with clinical decision-making in prostate cancer. Unlike frequentist approaches, which yield p-values and confidence intervals, Bayesian methods generate posterior probabilities that directly address patient-facing questions. This review synthesizes Bayesian applications across the prostate cancer continuum. Methods We conducted a narrative review informed by a structured search of PubMed, Web of Science, and the Cochrane Library. Searches yielded 465 records; after removal of 144 duplicates, 321 were screened and 11 representative studies were selected. The review was prepared with reference to the Scale for the Assessment of Narrative Review Articles (SANRA) guidance. Results Bayesian methods produced clinically interpretable probabilities and individualized predictions across prostate cancer care. Joint modeling of longitudinal prostate-specific antigen with time-to-event outcomes enabled dynamic recurrence forecasting, and risk-triggered active surveillance schedules reduced biopsies while maintaining timely upgrading detection. Bayesian network meta-analyses ranked systemic therapies and imaging tracers. Adaptive, model-based designs optimized radiotherapy and radioligand dosing, while population pharmacokinetic/pharmacodynamic frameworks supported hypothesis-generating personalization. Bayesian networks also improved causal adjustment in observational studies. Collectively, these applications enhanced evidence synthesis, decision transparency, patient communication, and model calibration. Conclusion Bayesian statistics complement frequentist methods by providing interpretable probabilities, incorporating prior knowledge, and supporting transparent clinical decisions. Familiarity with key concepts—posterior probabilities, credible intervals, prior specification, and calibration—enables clinicians to critically appraise Bayesian studies and communicate results effectively. As prostate cancer management increasingly emphasizes longitudinal monitoring and personalized treatment, Bayesian methods offer natural frameworks for evidence synthesis and decision-making under uncertainty. Microabstract Bayesian statistics offer clinically interpretable probabilistic frameworks for prostate cancer research. This review demonstrates applications across active surveillance, treatment sequencing, imaging synthesis, and adaptive trials, providing urologists with practical guidance for interpreting Bayesian studies and their direct patient-facing probability statements that complement traditional frequentist approaches.
Introduction Metastatic castration resistant prostate cancer (mCRPC) represents a late-stage, life-limiting phase of prostate cancer characterized by disease progression despite androgen deprivation therapy (ADT). With a median overall survival (OS) of approximately 25 months, prognosis remains poor. Although taxane chemotherapy, novel hormonal agents, PARP inhibitors, and radiopharmaceuticals are established options, patients who progress beyond these therapies have limited alternatives. Gemcitabine plus docetaxel (GEMDOC) has demonstrated antitumor activity in other solid tumors, but its efficacy in mCRPC is unclear. This study evaluates the safety and efficacy of biweekly GEMDOC in heavily pretreated mCRPC patients. Methods : We conducted a retrospective, single-institution cohort study of patients with histologically confirmed mCRPC treated at Emory University (2017-2025). Eligible patients had progressed after, declined, or were considered unsuitable for further approved mCRPC therapies or available clinical trials at the time GEMDOC was initiated. Patients received gemcitabine (1500 mg/m2) plus docetaxel (50 mg/m2) every other week (days 1 and 15 of a 28-day cycle). Data on demographics, prior therapies, PSA response, progression-free survival (PFS), OS, and treatment-related toxicities were extracted from electronic medical records. Univariate analyses evaluated outcomes by race, prior treatment, visceral metastasis, and de novo metastatic presentation. Results : Among 34 patients (median age: 72.5 years), 23 (67.7%) were White, 11 (32.3%) were Black. Most patients (91.2%) had prior docetaxel exposure. In our study, 35.3% presented with de novo metastatic disease, and 20.6% had visceral involvement. Patients received a median of 3 prior lines of therapy (range 1-6). PSA declines of ≥90%, ≥50%, and ≥30% were observed in 5.9%, 50%, and 64.7% of patients, respectively. Median PFS was 4.17 months, and median OS was 11.6 months. Grade 4 neutropenia occurred in two patients (6%), and grade 3 febrile neutropenia occurred in one patient (3%). Common grade 1–3 adverse events were myelosuppression and fatigue. Treatment was discontinued in 14 patients (41.2%) because of adverse events or patient preference, including requests for a treatment holiday. Growth factor support was required in 47.1% of patients. Among the remaining patients, 15 discontinued GEMDOC due to disease progression, while 5 completed six cycles of GEMDOC and were placed on surveillance. Conclusion : This retrospective study suggests that every other week GEMDOC may be a feasible salvage regimen with encouraging clinical activity and manageable toxicity in heavily pretreated patients with mCRPC who have exhausted or are ineligible for standard treatment options. Despite extensive prior taxane exposure and multiple previous lines of systemic therapy, clinically meaningful PSA responses and encouraging survival outcomes were observed in this real-world cohort. Prospective studies are warranted to further investigate these findings and better define the role of every other week GEMDOC in later-line mCRPC.
Background Enfortumab vedotin plus pembrolizumab (EV+P) received accelerated approval (AA) from the US Food and Drug Administration in April 2023 for cisplatin-ineligible patients with advanced urothelial cancer (aUC), followed by full approval (FA) in December 2023 regardless of cisplatin eligibility. While clinical trial data demonstrate durable treatment exposure, real-world treatment patterns after approval in large, multi-institutional populations remain less well characterized. We evaluated real-world time on treatment (rwToT) with first-line EV+P in a large US oncology network. Methods We conducted a retrospective cohort study using deidentified patient-level electronic health record-derived data from the Flatiron Health database, representing approximately 280 US cancer clinics. Included were patients with aUC initiating EV+P between April 5, 2023 and January 30, 2025. Follow-up extended through April 30, 2025. We summarized characteristics of EV+P users using descriptive statistics and computed time on treatment using the Kaplan-Meier method. A prespecified subgroup analysis evaluated patients initiating therapy between AA and FA to approximate a primarily cisplatin-ineligible population with longer potential follow-up. Results 510 aUC patients initiated first-line EV+P after AA. Median age was 74 years and 75.7% were male. Approximately 61.2% met real-world criteria for cisplatin ineligibility. At data cut-off, 60.4% (308/510) had discontinued EV+P, most commonly due to death (52.6%, 162/308), followed by initiation of second-line therapy (30.2%, 93/308), and treatment gap exceeding 60 days (17.2%, 53/308). Median rwToT was 7.5 months (IQR, 6.4-8.7). In the AA to FA subgroup, median rwToT was 7.1 months (IQR, 5.5-8.9). Among patients receiving subsequent therapy post EV+P, platinum–gemcitabine was the most common regimen (39.8%, 37/93). Conclusions In this large US cohort of primarily cisplatin-ineligible patients, rwToT with first-line EV+P approximated that observed in clinical trials, though modestly shorter. These findings likely reflect the greater clinical frailty of patients treated in routine practice. Continued follow-up will be needed to evaluate long-term outcomes and treatment sequencing following EV+P adoption.
BACKGROUND:Belzutifan, a hypoxia-inducible factor 2α (HIF-2α) inhibitor, is approved for advanced clear cell renal cell carcinoma (ccRCC) after immune checkpoint and antiangiogenic therapy, but real-world evidence is limited and none has correlated outcomes with tumor genomics. We evaluated effectiveness, tolerability, and genomic correlates in sporadic ccRCC. PATIENTS AND METHODS:We retrospectively identified patients with sporadic ccRCC treated with belzutifan between January 2021 and April 2026. Best response was investigator-assessed from routine radiology using RECIST 1.1 and reported for the full treated cohort (N = 88) and the evaluable subset (n = 75). Progression-free survival (PFS) and overall survival (OS) were estimated by Kaplan-Meier from initiation; associations with somatic VHL, PBRM1, BAP1, and SETD2 status were explored. A germline VHL syndrome cohort was described separately. RESULTS:Among 88 patients (median age 66 years; 70% male; of 78 with prior therapy, 88% prior immune checkpoint inhibitor, 94% prior VEGFR-TKI), objective response rate was 33.0% (95% CI, 23.3-43.8) overall and 38.7% among evaluable patients; disease control rate was 54.5% and 64.0%, respectively. Median PFS was 8.8 months (95% CI, 4.1-15.5); median OS was not reached after 16.1 months median follow-up. PFS did not differ by somatic VHL status (11.0 vs 3.2 months; HR 0.59; P = .22) or other 3p genes. The most common adverse events were anemia (71.6%; 29.5% grade ≥ 3) and hypoxia (18.2%; 10.2% grade ≥ 3); 5.6% discontinued for toxicity, with no treatment-related deaths. CONCLUSION:In the largest real-world sporadic ccRCC cohort treated with belzutifan to date, effectiveness and safety were consistent with registrational data in a broader, more representative population. Exploratory chromosome 3p analyses showed no significant differences but were underpowered.
Background : The oncologic value of regional lymph node dissection (LND) during surgery for renal cell carcinoma (RCC) remains controversial. Although LND improves pathological staging, its independent therapeutic benefit has not been consistently demonstrated in the contemporary era. Objective : To evaluate the association between LND and oncologic outcomes after nephrectomy while accounting for baseline treatment-selection bias using modern propensity score methodology. Design, Setting, and Participants : This multicenter retrospective cohort study included 1,078 consecutive patients undergoing partial or radical nephrectomy for localized or locally advanced RCC between 2017 and 2023 at five tertiary referral centers. Regional LND was performed in 234 patients (21.7%), whereas 844 underwent nephrectomy alone. Outcome Measurements and Statistical Analysis The primary endpoint was recurrence-free survival (RFS). Secondary endpoints included cancer-specific survival (CSS) and overall survival (OS). Cox proportional hazards models, propensity score adjustment, inverse probability of treatment weighting (IPTW), and predefined subgroup analyses were performed. Results : Patients undergoing LND presented with significantly larger tumors and more advanced clinical and pathological disease. On unadjusted analysis, LND was associated with inferior RFS (hazard ratio [HR] 2.56, 95% confidence interval [CI] 1.62–4.04) and CSS (HR 2.26, 95% CI 1.13–4.51). However, these associations were no longer significant following multivariable adjustment, propensity score adjustment, or IPTW. Independent predictors of recurrence included tumor size, pathological stage, WHO/ISUP grade, sarcomatoid differentiation, tumor necrosis, and metastatic disease, whereas LND was not independently associated with recurrence or survival. Conclusions : Regional LND does not appear to confer an independent oncologic benefit after adjustment for tumor biology and baseline selection bias. Its principal contemporary role remains accurate pathological staging, facilitating prognostic stratification and selection of patients for postoperative systemic therapy. Patient Summary In this multicenter study, lymph node dissection improved staging accuracy but was not independently associated with better cancer control or survival after accounting for differences in disease severity.Mini AbstractRegional lymph node dissection (LND) during nephrectomy for renal cell carcinoma remains controversial. In this multicenter cohort of 1,078 patients, LND was associated with worse unadjusted oncologic outcomes owing to adverse baseline tumor characteristics. After multivariable and propensity score-weighted analyses, LND was not independently associated with survival, supporting its contemporary role as a selective staging rather than therapeutic procedure.
INTRODUCTION:To better understand how treatment patterns, clinical outcomes, health-related quality of life, and healthcare resource utilization are impacted by initial prostate cancer diagnosis, prostate cancer family history, and race. PATIENTS:We conducted three subgroup analyses using the TRUMPET US registry of metastatic castration-resistant prostate cancer (mCRPC) patients: 1) initial diagnosis of non-metastatic hormone-sensitive prostate cancer (HSPC) versus de novo metastatic HSPC; 2) with prostate cancer family history versus none; 3) Caucasians versus African Americans. METHODS:Baseline characteristics, treatment patterns, health-related quality of life, and healthcare resource utilization were analyzed descriptively. Time-to-event outcomes were analyzed using the Kaplan-Meier method and Cox proportional hazards models, adjusted based on clinically important variables, including disease biology factors and selected variables showing large standardized mean differences between groups. RESULTS:This study included 832 patients with mCRPC. Patients with non-metastatic HSPC at initial diagnosis had a 32% lower risk of death than patients with de novo metastatic HSPC at initial diagnosis (adjusted HR: 0.68; 95% CI: 0.51, 0.91). Patients with prostate cancer family history had a significantly lower risk of death than patients with none (adjusted HR: 0.68; 95% CI: 0.51, 0.90). No statistically significant outcomes differences were identified between African American and Caucasian patients. Health-related quality of life changes were similar across all subgroups. CONCLUSION:Our analyses suggest that initial diagnosis and prostate cancer family history may meaningfully impact patients' survival and clinical outcomes. Future dedicated, prospective research should further elucidate how each of these factors affectclinical outcomes in the mCRPC context.
BACKGROUND:Ultrasensitive assays enable detection of prostate-specific antigen (PSA) levels below 0.2 ng/mL, previously considered undetectable, allowing a more refined assessment of treatment response in metastatic hormone-sensitive prostate cancer (mHSPC). We evaluated the association between early achievement of ultra-low PSA levels and radiographic progression-free survival (rPFS). MATERIALS AND METHODS:Patients received first-line androgen deprivation therapy (ADT) alone, ADT plus docetaxel, or ADT combined with androgen receptor pathway inhibitors (ARPIs). PSA levels were measured at baseline and during the first 3 months. Patients were stratified according to the lowest PSA level achieved within 3 months: < 0.02 ng/mL, 0.02 to 0.2 ng/mL, and > 0.2 ng/mL. rPFS was estimated using the Kaplan-Meier method. RESULTS:Of 347 patients, 323 were included in the analysis. Median age was 68 years, and 51.7% had ECOG performance status 0. High-volume disease was present in 50.5%, and 76.5% had synchronous metastases. Treatment included ADT alone (25.1%), ADT plus docetaxel (24.5%), and ARPI-based therapy (50.5%). Within 3 months, 15.5% achieved PSA < 0.02 ng/mL, 18.9% had PSA 0.02 to 0.2 ng/mL, and 65.6% had PSA > 0.2 ng/mL. Ultra-low PSA responses were more frequent with ARPI-based therapy (20.9%) compared with ADT alone (12.4%) and ADT plus docetaxel (7.6%). Median rPFS was 34.2 months (95% confidence interval, 27-40). Five-year rPFS rates were 89%, 80%, and 18% for PSA < 0.02, 0.02 to 0.2, and ≥ 0.2 ng/mL, respectively (P < .001). CONCLUSION:Early achievement of ultra-low PSA (< 0.02 ng/mL within 3 months) is strongly associated with prolonged rPFS in mHSPC and may serve as a novel early surrogate marker of treatment efficacy.
Background Marker-negative germ cell tumors (GCT) account for up to 40% of metastatic disease, making treatment monitoring and surveillance challenging. The utility of circulating tumor DNA (ctDNA) in teratoma and somatic-type malignancies (SM) remains undefined. Methods In this retrospective study, the GCT database at a tertiary referral center was queried to identify patients with available ctDNA reports and evidence of radiological progression without tumor marker elevation, or normal pre-orchiectomy tumor markers. ctDNA, stratified as either positive or negative was studied in conjunction with radiology and histology status to determine concordance. Serial trends of mean tumor molecules/ml across various therapeutic interventions and relapse were also investigated. Results Between December 2024 and February 2026, 34 patients with marker-negative germ cell tumors (GCTs) and 70 ctDNA assessments were identified. The most common histology was seminoma (15, 44%), followed by somatic-type malignancy (SM) (6, 18%). Pure teratoma was present in 3 patients (9%). ctDNA was undetectable in 35/38 (92.1%) assessments of response and detectable in 23/25 (92.0%) assessments of progression. One patient each with neuroendocrine somatic transformation and growing teratoma syndrome progressed with undetectable ctDNA. Conclusion ctDNA demonstrates high concordance with disease status in marker-negative non-teratomatous GCT, with potential utility in SM.
PARP inhibitors (PARPi) combined with androgen-receptor signaling inhibitors (ARSI) improve radiographic progression-free survival (rPFS) in homologous-recombination-repair (HRR)-altered metastatic prostate cancer, but effects across disease states and genomic subgroups remain uncertain. We searched MEDLINE, Embase, CENTRAL, Web of Science, and ClinicalTrials.gov through June 2026 for randomized trials of PARPi plus ARSI versus the same ARSI alone in HRR-altered metastatic prostate cancer. Trial-level log hazard ratios were pooled using REML random-effects models with Hartung-Knapp confidence intervals. Disease-state and BRCA/non-BRCA comparisons, including a paired ratio-of-hazard ratios [HRs] analysis, were exploratory. Five phase III trials included 2343 men. PARPi plus ARSI improved rPFS overall (HR 0.56, 95% confidence intervals 0.43-0.72). Pooled HRs were 0.36 (0.21-0.63) for BRCA-altered disease and 0.75 (0.51-1.09) for the heterogeneous non-BRCA group. The exploratory paired BRCA/non-BRCA ratio of HRs was 0.54 (0.32-0.90; P = .031), assuming zero covariance. Disease-state estimates were imprecise (mHSPC 0.56, 0.10-3.11; mCRPC 0.55, 0.29-1.07). The latest pooled overall-survival estimate was 0.75 (0.61-0.93; I² = 25%), but 2 trials remained interim. Grade ≥ 3 adverse events were consistently increased. PARPi plus ARSI improves rPFS in HRR-altered metastatic prostate cancer. The relative effect appears larger in BRCA-altered disease, but the interaction remains exploratory and non-BRCA alterations are biologically heterogeneous. Disease-state estimates do not support comparative inference. Overall-survival evidence suggests a signal, not definitive benefit, and must be balanced against increased toxicity.
Fibroblast growth factor receptor (FGFR) alterations have emerged as clinically actionable biomarkers in urothelial carcinoma (UC), particularly following the introduction of FGFR-targeted therapies for patients with advanced disease. Activating mutations, gene fusions, copy number alterations, and expression changes involving FGFR2 and, especially, FGFR3 contribute to urothelial tumorigenesis through persistent activation of oncogenic signaling pathways and are enriched in specific molecular subtypes. Because these alterations occur at different molecular levels, their accurate detection requires complementary diagnostic methodologies rather than a single analytical platform. This review summarizes the current landscape of FGFR alteration testing in UC, with a particular focus on the analytical principles, strengths, limitations, and clinical applications of tissue- and liquid biopsy-based approaches. Conventional techniques, including DNA- and RNA-based next-generation sequencing, PCR-based companion diagnostic assays, fluorescence in situ hybridization, and immunohistochemistry, are critically discussed together with emerging liquid biopsy strategies for longitudinal disease monitoring and resistance assessment. We also review the current clinical indications for FGFR testing, its role in patient selection for targeted therapies such as erdafitinib, and the molecular mechanisms underlying acquired resistance. Finally, future perspectives involving artificial intelligence, single-cell and spatial transcriptomics, multi-omics integration, and novel biomarker discovery are examined as potential strategies to further refine precision oncology in UC. Collectively, accurate and standardized detection of FGFR alterations represents a fundamental component of contemporary molecular pathology and is expected to play an increasingly important role in guiding personalized therapeutic strategies for patients with UC.
Introduction There is a need for contemporary data on clinical outcomes following Bacillus Calmette-Guérin (BCG) treatment in patients with high-risk (HR) non-muscle-invasive bladder cancer (NMIBC). This study evaluated recurrence and survival outcomes among patients with HR-NMIBC who received BCG in the United States. Methods Surveillance, Epidemiology and End Results-Medicare data were used to identify patients aged ≥65 years with a primary diagnosis of HR-NMIBC who received BCG therapy (initiation date was the index date). Post-BCG recurrence was assessed overall and by recurrence type: local NMIBC recurrence, progression to muscle-invasive bladder cancer (MIBC), and distant metastasis (DM). Event-free survival (EFS; time to the first recurrence event or death) and overall survival (OS; time to death) were estimated using Kaplan-Meier analysis. Cystectomy use following recurrence was also evaluated. Results A total of 5,490 patients with HR-NMIBC who received BCG were included in this study, of whom 33.6% had high-grade Ta, 55.0% had T1 (± Ta), and 11.4% had Tis (±Ta/T1) at initial diagnosis. Over a median follow-up of 2.9 years, 2,178 (39.7%) patients experienced recurrence, with 97.2% occurring within the first 5 years after BCG initiation. Recurrence rates for local NMIBC recurrence, progression to MIBC, and DM increased from 15.9%, 4.1%, and 3.7% at 1 year to 33.6%, 15.9%, and 16.7% at 10 years, respectively. Recurrence rates were similarly high among patients with Tis (42.1%) and T1 (40.6%) disease. Among patients with recurrence, 312 (14.3%) underwent cystectomy, 83.3% of which were performed within 1 year after recurrence. Conclusions In this population-based study, patients with HR-NMIBC experienced substantial recurrence burden following BCG treatment, with the majority of recurrences occurring within 5 years after BCG initiation. These findings underscore the need for improved strategies to effectively delay or prevent disease recurrence in patients with HR-NMIBC. Micro abstract This study evaluated recurrence and survival in patients aged ≥65 years with high-risk non-muscle-invasive bladder cancer (HR-NMIBC) receiving Bacillus Calmette-Guérin (BCG). Among 5,490 patients, 2,178 (39.7%) experienced recurrence over a median of 2.9 years, with 97.2% occurring within the first 5 years after BCG initiation. These findings underscore the need for improved strategies to delay/prevent disease recurrence in HR-NMIBC.
INTRODUCTION:Non-clear cell renal cell carcinoma (nccRCC) comprises heterogeneous cancers historically managed using evidence extrapolated from clear cell RCC. Current guidelines support histology-guided treatment, but real-world adoption of systemic strategies and cytoreductive nephrectomy remains incompletely characterized. We assessed temporal trends in systemic treatment and cytoreductive surgery and identified predictors of treatment allocation in metastatic nccRCC. METHODS:We used the National Cancer Database to identify adults diagnosed with metastatic nccRCC from 2016 to 2022. Patients were classified as receiving targeted therapy (TT) only, immunotherapy (IO) only, IO + TT, or no documented systemic therapy. Temporal trends were assessed using annual treatment proportions and estimated annual percentage change (EAPC). Multivariable logistic regression evaluated predictors of systemic treatment allocation and receipt of cytoreductive surgery. RESULTS:Among 3677 patients, 30.9% received TT only, 19.3% IO only, 13.7% IO + TT, and 36.1% had no documented systemic therapy. Among treated patients, TT use decreased over time (EAPC -23.46%, 95% CI -25.80 to -21.05; P < .001), whereas IO only (EAPC +32.26%, 95% CI +6.21 to +64.71; P = .022) and IO + TT (EAPC +30.70%, 95% CI +25.00 to +36.66; P < .001) increased. Cytoreductive surgery declined (EAPC -8.89%, 95% CI -12.04 to 5.64; P = .001). Later year of diagnosis was associated with IO-based treatment, with differential use across histologic subtypes. CONCLUSIONS:Between 2016 and 2022, treatment patterns for metastatic nccRCC in the US shifted from TT toward IO-based regimens, while cytoreductive surgery declined, reflecting evolving real-world management of this heterogeneous disease.
