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Background: Triplet therapy, androgen receptor signaling inhibitors (ARSIs) plus docetaxel plus androgen-deprivation therapy (ADT), is a novel guideline-recommended treatment for metastatic hormone-sensitive prostate cancer (mHSPC). However, the optimal selection of the patient most likely to benefit from triplet therapy remains unclear. Methods: We performed a systematic review, meta-analysis, and network meta-analysis to assess the oncologic benefit of triplet therapy in mHSPC patients stratified by disease volume and compare them with doublet treatment regimens. Three databases and meeting abstracts were queried in March 2023 for randomized controlled trials (RCTs) evaluating patients treated with systemic therapy for mHSPC stratified by disease volume. Primary interests of measure were overall survival (OS). We followed the PRISMA guideline and AMSTAR2 checklist. Results: Overall, eight RCTs were included for meta-analyses and network meta-analyses (NMAs). Triplet therapy outperformed docetaxel plus ADT in terms of OS in both patients with high-(pooled HR: 0.73, 95%CI 0.64–0.84) and low-volume mHSPC (pooled HR: 0.71, 95%CI 0.52–0.97). There was no statistically significant difference between patients with low- vs. high-volume in terms of OS benefit from adding ARSI to docetaxel plus ADT (p = 0.9). Analysis of treatment rankings showed that darolutamide plus docetaxel plus ADT (90%) had the highest likelihood of improved OS in patients with high-volume disease, while enzalutamide plus ADT (84%) had the highest in with low-volume disease. Conclusions: Triplet therapy improves OS in mHSPC patients compared to docetaxel-based doublet therapy, irrespective of disease volume. However, based on treatment ranking, triplet therapy should preferably be considered for patients with high-volume mHSPC while those with low-volume are likely to be adequately treated with ARSI + ADT. [ABSTRACT FROM AUTHOR]

Renal cell carcinoma (RCC) represents 2% of all diagnosed malignancies worldwide, with disease recurrence affecting 20% to 40% of patients. Existing prognostic recurrence models based on clinicopathological features continue to be a subject of controversy. In this meta‐analysis, we summarized research findings that explored the correlation between clinicopathological characteristics and post‐surgery survival outcomes in non‐metastatic RCC patients. Our analysis incorporates 99 publications spanning 140 568 patients. The study's main findings indicate that the following clinicopathological characteristics were associated with unfavorable survival outcomes: T stage, tumor grade, tumor size, lymph node involvement, tumor necrosis, sarcomatoid features, positive surgical margins (PSM), lymphovascular invasion (LVI), early recurrence, constitutional symptoms, poor performance status (PS), low hemoglobin level, high body‐mass index (BMI), diabetes mellitus (DM) and hypertension. All of which emerged as predictors for poor recurrence‐free survival (RFS) and cancer‐specific survival. Clear cell (CC) subtype, urinary collecting system invasion (UCSI), capsular penetration, perinephric fat invasion, renal vein invasion (RVI) and increased C‐reactive protein (CRP) were all associated with poor RFS. In contrast, age, sex, tumor laterality, nephrectomy type and approach had no impact on survival outcomes. As part of an additional analysis, we attempted to assess the association between these characteristics and late recurrences (relapses occurring more than 5 years after surgery). Nevertheless, we did not find any prediction capabilities for late disease recurrences among any of the features examined. Our findings highlight the prognostic significance of various clinicopathological characteristics potentially aiding in the identification of high‐risk RCC patients and enhancing the development of more precise prediction models. [ABSTRACT FROM AUTHOR]

In stage-specific analyses of 98,142 renal cell carcinoma patients, married status independently predicted higher nephrectomy rates in males and females. In stage IV, married status predicted higher systemic therapy rate in males, but not in females. Married males exhibited lower cancer specific mortality across all stages; married females only in stages I and III (all P ≤ .02). Introduction: The association between treatment rates and cancer specific mortality (CSM) according to married status in male and female clear cell renal cell carcinoma (ccRCC) patients across all stages is unknown. Patient and Methods: Using the Surveillance, Epidemiology, and End Results database (2004-2020), ccRCC patients were stratified according to married status (married vs. unmarried). Logistic regression models addressed treatment rates; Cox regression models addressed CSM rates. Results: Of 98,142 patients, 43,999 (72%) males and 20,287 (55%) females were married. In stage-specific analyses, married status independently predicted higher nephrectomy rates in males and females (all P ≤ .03). In stage IV, married status predicted higher systemic therapy rate in males (P < .001), but not in females. In survival analyses, married males exhibited lower CSM rates relative to unmarried males (all P ≤ .02). Conversely, married females exhibited lower CSM rates only in stages I and III (all P ≤ .02), but not in stages II and IV. In subgroup analyses of T1aN0M0 patients, married status was associated with higher partial nephrectomy rates in both males and females (all P ≤ .005). Conclusion: In ccRCC, married status invariably predicts higher rates of guideline recommended surgical management (nephrectomy and partial nephrectomy). Moreover, even after adjustment for treatment type, married status independently predicted lower CSM rates in males across all stages. However, the effect of married status in females is only operational in stages I and III. Lack of association between married status in stages II and IV may potentially be explained by stronger association with treatment assignment which reduces the residual effect on survival. [ABSTRACT FROM AUTHOR]

In clear-cell metastatic renal cell carcinoma (ccmRCC) patients, intensified treatment (systemic therapy [ST] + cytoreductive nephrectomy [CN]) does not result in higher other-cause mortality (OCM), than when ST is used alone. Conversely, a strong association with lower cancer-specific mortality was recorded in ST + CN patients, relative to their ST alone counterparts, even after strictest statistical adjustments. Background: The effect of treatment intensification (systemic therapy [ST] + cytoreductive nephrectomy (CN) vs. ST alone) is unknown regarding rates of other-cause mortality (OCM) in clear-cell metastatic renal cell carcinoma (ccmRCC). We hypothesized that intensified treatment (ST + CN) may result in higher OCM, than when ST is used alone. Methods: Within the Surveillance, Epidemiology, and End Results database, all ccmRCC patients treated 2010-2018 either with ST + CN or ST alone were identified. Propensity score matching (PSM), cumulative incidence plots, multivariable competing risks regression analyses and 6 months' landmark analyses addressed OCM and cancerspecific mortality (CSM) according to treatment status. Results: Of 2271 ccmRCC patients, 1233 (54%) were treated with ST + CN vs 1038 (46%) with ST alone. After 1:1 PSM, OCM was 5.3 vs. 4.6 % (P = .5) and CSM was 73.4 vs. 88.4% (P < .001) in ST + CN vs. ST alone patients. In multivariable competing risks regression, the combination of ST and CN was not associated with higher OCM (HR 1.3; 95% CI 0.8-2.1; P = .4), vs. ST alone. However, the combination of ST and CN was independently associated with lower CSM (HR 0.5; 95% CI 0.5-0.6; P < .001), vs. ST alone. After 6 months' landmark analyses, these multivariable associations remained unchanged. Conclusions: The current study indicates no OCM-disadvantage in ST + CN ccmRCC patients, relative to their ST alone counterparts. Conversely, a strong association with lower CSM was recorded in ST + CN patients, relative to their ST alone counterparts. These associations are robust and remained unchanged after strictest statistical adjustment including control for immortal time bias. [ABSTRACT FROM AUTHOR]

We tested for the prognostic significante of radiographic N-stage in metastatic renal cell carcinoma (mRCC) patients with low metastatic burden (single metastatic site). After multivariable adjustment, radiographic N1 status was an independent predictor of higher cancer-specific mortality (CSM). In consequence, consideration of radiographic lymph node invasion might be of great value in this specific population of mRCC patients. Purpose: To test the prognostic significance of radiographic cN-stage in metastatic renal cell carcinoma (mRCC) patients with low metastatic burden (1 site of metastasis), relying on the Surveillance, Epidemiology, and End Results database (SEER 2010-2020). Methods: Included were mRCC patients with 1 site of metastasis, treated with systemic therapy without cytoreductive nephrectomy (CN). Kaplan-Meier plots and multivariable Cox-regression models addressed cancer-specific mortality (CSM) according to radiographic cN-stage (ccN1 vs. ccN0). Separate subgroup analyses were performed, addressing radiographic N-stage in patients with distinct histology (clear-cell vs. RCC not otherwise specified [RCC NOS]). Results: Of 1756 mRCC patients, 545 (31%) were radiographic cN1. Overall, the median CSM-free survival of the cohort was 11 months. Median CSM-free survival was 8 vs. 14 months in radiographic cN1 vs. cN0 mRCC patients (HR 1.49, P < .0001). In multivariable Cox regression analyses, radiographic cN1 status was an independent predictor of higher CSM (HR 1.39; P = .01). In subgroup analyses, addressing patients with clear-cell histology and patients with RCC NOS separately, radiographic cN1 status remained independently associated with a higher CSM in both groups (clear-cell: HR 1.36; P = .03; RCC NOS: HR 2.06; P = .009). Conclusion: In mRCC patients with low metastatic burden, presence or absence of radiographic lymph node invasion results in a clinically meaningful discrimination between those with poor prognosis and others. In consequence, consideration of radiographic lymph node invasion might be of great value in this specific population of mRCC patients. [ABSTRACT FROM AUTHOR]