Many liquid biomarkers have entered clinical practice with the praise to improve the detection of clinically significant prostate cancer (csPCa), helping avoid unnecessary prostate biopsies. We aimed to assess the diagnostic accuracy of multianalyte biomarkers for csPCa detection using multiple thresholds. A comprehensive literature search was done through PubMed, Web of Science, and Scopus in March 2023 for prospective and retrospective studies reporting the diagnostic performance of liquid biomarkers for detecting csPCa. The outcomes of interest were the diagnostic performance of liquid biomarkers for csPCa detection and identification of optimal thresholds for each biomarker. Overall, 49 studies were eligible for this meta-analysis. Using each representative threshold based on the Youden Index, the pooled sensitivity and specificity for detecting csPCa were 0.85 and 0.37 for prostate cancer gene 3 (PCA3), 0.85 and 0.52 for prostate health index (PHI), 0.87 and 0.58 for four kallikrein (4K), 0.82 and 0.56 for SelectMDx, 0.85 and 0.54 for ExoDx, and 0.82 and 0.59 for mi prostate score (MPS), respectively. The diagnostic odds ratio was highest for 4K (8.84), followed by MPS (7.0) and PHI (6.28). According to the meta-analysis incorporating multiple thresholds, the corresponding sensitivity was 0.77 for 4K, 0.69 for PHI, and 0.63 for PCA3; specificity was 0.72 for PHI, 0.70 for 4K, and 0.69 for PCA3. Regarding the detection of csPCa, 4K had the highest diagnostic performance among the commercial liquid biomarkers. Based on the optimal thresholds calculated by the present meta-analysis, 4K had the highest sensitivity and PHI had the highest specificity for detecting csPCa. Nevertheless, clinical decision-making requires combination strategies between liquid and imaging biomarkers. Novel biomarkers for prostate cancer detection were useful for more accurate diagnosis of clinically significant prostate cancer to avoid unnecessary biopsies.

Purpose: To analyze and summarize the efficacy of immune checkpoint inhibitor (ICI) alone or in combination therapy for renal cell carcinoma (RCC) and urothelial carcinoma (UC) stratified by sex. Methods: Three databases were queried in October 2022 for randomized controlled trials (RCTs) analyzing RCC and UC patients treated with ICIs. We analyzed the association between sex and the efficacy of ICIs in RCC and UC patients across several clinical settings. The outcomes of interest were overall survival (OS) and progression-free survival for the metastatic setting and disease-free survival (DFS) for the adjuvant setting. Results: Overall, 16 RCTs were included for meta-analyses and network meta-analyses. In the first-line treatment of metastatic RCC (mRCC) and UC (mUC) patients, ICI-based combination therapies significantly improved OS compared to the current standard of care, regardless of sex. Adjuvant ICI monotherapy reduced the risk of disease recurrence in female patients with locally advanced RCC (pooled hazard ratio [HR]: 0.71, 95% confidence interval [CI] 0.55–0.93) but not in male patients, and, conversely, in male patients with muscle-invasive UC (pooled HR: 0.80, 95%CI 0.68–0.94) but not in female patients. Treatment ranking analyses in the first-line treatment of mRCC and mUC showed different results between sexes. Of note, regarding adjuvant treatment for RCC, pembrolizumab (99%) had the highest likelihood of improved DFS in males, whereas atezolizumab (84%) in females. Conclusions: OS benefit of first-line ICI-based combination therapy was seen in mRCC and mUC patients regardless of sex. Sex-based recommendations for ICI-based regimens according to the clinical setting may help guide clinical decision-making.

This study aimed to assess both efficacy and safety outcomes of lowering the dose of BCG compared to intravesical chemotherapies in non-muscle-invasive bladder cancer (NMIBC) patients using a systematic review, meta-analysis, and network meta-analysis approach. A comprehensive literature search was performed through Pubmed®, Web of Science™, and Scopus® in December 2022 to identify randomized controlled trials comparing the oncologic and/or safety outcomes of reduced dose intravesical BCG and/or intravesical chemotherapies according to the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) statement. The outcomes of interest were risk of recurrence, progression, treatment-related adverse events, and discontinuation. Overall, 24 studies were eligible for quantitative synthesis. Among 22 studies that adopted induction followed by maintenance intravesical therapy, with reference to the lower-dose BCG, epirubicin was associated with a significantly higher risk of recurrence (Odds ratio [OR]: 2.82, 95% CI: 1.54-5.15), but not other intravesical chemotherapies. There were no significant differences in risk of progression among the intravesical therapies. On the other hand, standard-dose BCG was associated with a higher risk of any AEs (OR: 1.91, 95% CI: 1.07-3.41) but other intravesical chemotherapies had a comparable risk of AEs compared to lower-dose BCG. The discontinuation rate did not significantly differ between lower-dose and standard-dose BCG (OR: 1.40, 95% CI: 0.81-2.43) as well as other intravesical. According to the surface under the cumulative ranking curve, gemcitabine, and standard-dose BCG were preferable to lower-dose BCG in terms of recurrence risk; gemcitabine was also preferable to lower-dose BCG in terms of risk of AEs. In patients with NMIBC, lowering the dose of BCG decreases the risks of AEs and discontinuation rate compared to standard-dose BCG, but there is no difference in these endpoints compared to other intravesical chemotherapies. Standard-dose of BCG is preferred for all intermediate and high-risk NMIBC patients based on oncologic efficacy; however, lower-dose BCG and intravesical chemotherapies, especially gemcitabine, could be considered a reasonable alternative to BCG in selected patients who suffer from significant AEs or in case standard-dose BCG is not available.