Network meta-analysis of combination strategies in metastatic hormone-sensitive prostate cancer.

ABSTRACT: This study compared different doublet and triplet therapies for efficacy and safety in metastatic hormone-sensitive prostate cancer (mHSPC). PubMed, EMBASE, and the Cochrane Library were comprehensively searched for eligible randomized controlled trials (RCTs) published from inception to October 2023. Interventions included abiraterone, apalutamide, enzalutamide, docetaxel, darolutamide, and androgen deprivation therapy (ADT), either as doublet or triplet therapies. The outcomes examined were overall survival (OS), progression-free survival (PFS), castration-resistant prostate cancer (CRPC)-free survival, time to symptomatic skeletal event (SSE), and toxicity. The surface under the cumulative ranking curve (SUCRA) was determined to identify the preferred treatments. Ten RCTs were included. The combination of darolutamide, docetaxel, and ADT had the highest SUCRA of 84.3 for OS, followed by combined abiraterone, docetaxel, and ADT (SUCRA = 71.6). The highest SUCRAs for PFS were observed for triplet therapies (abiraterone, docetaxel, and ADT [SUCRA = 74.9], followed by enzalutamide, docetaxel, and ADT [SUCRA = 74.3]) and other androgen receptor axis-targeted therapy-based doublet therapies (SUCRAs: 26.5-59.3). Darolutamide, docetaxel, and ADT had the highest SUCRAs, i.e., 80.8 and 84.0 regarding CRPC-free survival and time to SSE, respectively. Regarding Grade >3 adverse events (AEs), the SUCRAs of triplet therapies (SUCRAs: 14.8-31.5) were similar to that of docetaxel and ADT (SUCRA = 39.5). Three studies had a low risk of bias in all categories; the remaining studies had at least an unclear risk of bias in at least one category. Triplet therapy demonstrated potentially enhanced effectiveness than doublet therapy in mHSPC, with acceptable safety concerns. Darolutamide might be the optimal option for triplet therapy in combination with docetaxel and ADT.

Prognostic value of primary tumor surgery in seminoma patients with distant metastasis at diagnosis: a population-based study.

The aims of this study were to determine the prognostic value of primary tumor surgery and identify optimal candidates for such surgery among patients with seminoma and distant metastasis at diagnosis. We identified 521 patients with seminoma and distant metastasis at diagnosis between 2004 and 2014 from the Surveillance, Epidemiology, and End Results database. Among these patients, 434 had undergone surgery, whereas 87 had not. The prognostic value of primary tumor surgery was assessed by Kaplan-Meier methods, log-rank analyses, and multivariate Cox's proportional hazards model. Survival curves and forest plots were also plotted. Survival analysis indicated that patients who underwent surgery had a better 5-year overall survival and cancer-specific survival than those who did not. Multivariate analyses demonstrated that primary tumor surgery is an independent prognostic factor for overall survival and cancer-specific survival, along with age at diagnosis, M stage, and marital status. In addition, primary tumor surgery still had considerable prognostic value in the subgroup of patients with lymph node metastasis. Further, forest plots demonstrated that patients with M1a stage, N1 or N2-3 stage, and a younger age at diagnosis (<60 years) may benefit from primary tumor surgery. In conclusion, our findings indicate that primary tumor surgery is correlated with improved survival in patients with seminoma and distant metastasis. Furthermore, primary tumor surgery is an independent prognostic indicator for patients with seminoma and distant metastasis.

Important Therapeutic Considerations in T1b Penile Cancer: Prognostic Significance and Adherence to Treatment Guidelines.

BACKGROUND: The clinical implications and contemporary management of T1b penile cancer are unknown. National treatment guidelines advocate surgical lymph node examination (SLNE) for T1b disease. OBJECTIVE: The aim of this study was to evaluate the prognosis of T1b disease and adherence to corresponding treatment guidelines. METHODS: We analyzed 296 patients from two academic centers, and 1263 patients from the Surveillance, Epidemiology, and End Results (SEER) registry (median follow-up 48.3 and 21 months, respectively). Multivariate Cox and Fine-Gray regressions were applied for penile cancer-specific survival (PCSS) analyses. RESULTS: In the academic center cohort, 28.3% of T1 patients had T1b disease, all of whom underwent SLNE. Nodal metastases were detected in 86.7% of T1b patients and 13.2% of T1a patients (p < 0.001). Using T1a as a reference, PCSS was significantly poorer in the T1b patients, with an adjusted hazard ratio (aHR) of 4.10 (p = 0.03). In the SEER cohort, 16.8% of T1 patients were classified as T1b. SLNE was performed in 21.7% of the T1b patients versus 38.2% of the T2 patients (p = 0.002). The probability of nodal metastases was 2.23-fold higher in T1b patients than in T1a patients (p < 0.001). In clinical N0M0 patients without SLNE, compared with T1a disease, T1b was associated with an aHR of 4.40 and a subdistribution HR of 4.53 for PCSS (both p = 0.003). CONCLUSIONS: T1b penile cancer is strongly associated with nodal metastases and adverse PCSS, and is poorly managed according to guidelines recommended in the nationwide registry.