Purpose: To evaluate the efficacy and safety of poly (ADP-ribose) polymerase inhibitors (PARP inhibitors [PARPi]) in managing advanced prostate cancer (PCa) in patients with and without homologous recombination repair (HRR) genomic alterations (GAs). Methods: Following PRISMA 2020 guidelines, we systematically searched PubMed, Google Scholar, and ScienceDirect for studies published through January 2025. Randomized controlled trials and observational studies assessing PARPi in advanced PCa with documented HRR GA status were included. Primary outcomes included radiographic progression-free survival (rPFS) and overall survival (OS); secondary outcomes were prostate specific antigen 50 response and safety. Data were pooled using a random-effects meta-analysis model, with hazard ratios (HRs) and 95% confidence intervals (CIs) calculated for time-to-event outcomes. Results: Of 363 articles identified, 6 studies met the inclusion criteria. In patients harboring HRR GAs, PARPi significantly improved rPFS (HR 0.61; 95% CI 0.55-0.68; P < .00001) and OS (HR 0.82; 95% CI 0.69-0.96; P = .01) compared with the control. Subgroup analysis revealed that this improvement in survival was predominantly driven by BRCA1/2 alterations. Patients carrying non-BRCA HRR GAs (eg, ATM, CHECK2, CDK12, PALB2, FANCA, BRIP1, HDAC2) receiving PARPi did not have a significant improvement in their rPFS compared with the controls. Similarly, HRR-negative patients had no significant improvement in rPFS (HR 1.21; 95% CI 0.97-1.51; P = .10) or OS (HR 0.93; 95% CI 0.78-1.10; P = .40). Conclusions: PARPi confer superior efficacy over standard therapy in advanced PCa harboring BRCA1/2 GAs, underscoring the need for routine genomic profiling. In patients with other HRR alterations or HRR-negative PCa, the effect size has wide CIs, indicating the possibility of efficacy of PARPi in these patients. However, this survival does not reach statistical significance.

Background: Penile squamous cell carcinoma (SCC) is now categorized based on human papillomavirus (HPV) status as HPV associated (SCCa) or HPV-independent. While most HPV-independent cases are of the usual type (Usual-SCCi), the prognostic significance of this subclassification—particularly between Usual-SCCi and other SCC HPV-independent variants (Variant-SCCi)—remains unclear. Materials and Methods: Using SEER data (2000–2021), patients with penile SCC were categorized into Usual-SCCi, Variant-SCCi (verrucous, papillary, and sarcomatoid), and SCCa groups. Cancer-specific survival (CSS) was evaluated using Kaplan–Meier estimates and Cox proportional hazard regression adjusted for demographic and clinical factors, with Firth’s penalized likelihood correction applied when appropriate. Temporal trends and subtype-specific outcomes were also analyzed. Results: Among 6332 patients, 5706 (90.1%) were Usual-SCCi, 416 (6.6%) were Variant-SCCi, and 210 (3.3%) were SCCa. Overall, 5-year CSS (proportion of patients (%) [95% CI]) was the highest in Variant-SCCi (90.9% [87.8–94.0]), compared to Usual-SCCi (73.7% [72.4–75.0]) and SCCa (71.5% [63.3–80.8). Within Variant-SCCi, verrucous SCC had the most favorable outcome (94.1% [91.3–97.0]), followed by papillary (81.9% [68.2–98.4]) and sarcomatoid (63.4% [47.4–84.7]). Multivariable analysis confirmed verrucous SCC as being independently associated with significantly lower cancer-specific mortality (HR: 0.31 [95% CI, 0.20–0.45]; p < 0.001). Time-stratified analysis revealed that in the latter half of the study period, SCCa outcomes improved markedly, and no statistically significant differences in CSS were observed among the SCCa, papillary, and Usual-SCCi groups, leaving verrucous SCC as the only subtype with consistently superior survival (p < 0.001). Conclusions: The CSS of SCCa improved over time to become equivalent to those of the SCCi subtypes except for the verrucous SCCi variant, which had a significantly better CSS. Our study clearly demonstrates a temporal shift toward improved CSS in the SCCa subtype, which may be related to increased awareness following recognition as a separate entity in the WHO 2022 classification and other factors.

Recent Phase III trials using immunotherapy agents in perioperative setting for muscle-invasive bladder cancer (MIBC) have reshaped treatment paradigms. Traditional hazard ratios, while statistically robust, may mask modest absolute survival gains, complicating informed decision-making for clinicians and patients alike. This study aims to utilize restricted mean survival time (RMST) analysis to provide more intuitive interpretations of survival benefits and facilitate development of a framework for comparing efficacy, toxicity, and costs across three pivotal trials. Overall survival (OS), disease free survival (DFS) and adverse effects (AE) data were extracted from recently published Phase III MIBC trials reporting results by HR: NIAGARA (perioperative durvalumab), CheckMate-274 (adjuvant nivolumab) and AMBASSADOR (adjuvant pembrolizumab). Using reconstructed individual patient data, RMST was calculated at a 42-month truncation. Costs were sourced from U.S. Medicare prices and calculated using each study's median treatment duration. DFS-RMST differences at 42 months were: 3.39 months (95% CI: 1.4-5.39) for NIAGARA, 4.05 months (95% CI: 1.33-6.78) for CheckMate-274, and 3.97 months (95% CI: 1.3-6.65) for AMBASSADOR. OS-RMST differences were: 1.84 months (95% CI: 0.37-3.37) for NIAGARA, 2.56 months (95% CI: 0.54-4.58) for CheckMate-274, and 0.95 months (95% CI: -1.21 to 3.15) for AMBASSADOR. Cost per month of survival gained ranged from $43,460 to $49,832 for DFS and $52,387 to $207,374 for OS across trials. Our RMST-based analysis highlights the minimal real-world survival benefits and provides more intuitive and clinically relevant interpretations than traditional hazard ratios. Our visualization framework offers an intuitive approach to assist clinicians and patients in making informed decisions.