Oncologic Outcomes of Patients with Immune Checkpoint Inhibitor Resistant Urothelial Carcinoma Treated with Enfortumab Vedotin and the Impact of Neutrophil-to-Lymphocyte Ratio and Dysgeusia on Overall Survival: A Retrospective Multicenter Cohort Study in Japan.

Randomized phase III trial results have demonstrated enfortumab vedotin (EV), an antibody-drug conjugate (ADC) consisting of an anti-Nectin-4 human IgG1 monoclonal antibody and monomethyl auristatin E, is a useful treatment for patients with locally advanced or metastatic urothelial carcinoma (la/mUC) that progressed after immune checkpoint inhibitor (ICI) therapies. This multicenter retrospective cohort study aimed to identify predictive factors for the efficacy of EV therapy and prolonged overall survival (OS) of patients in clinical practice. This study included patients with la/mUC who received ICI treatment. Patients who subsequently received EV treatment, those who received non-EV chemotherapy, and those who received no treatment were defined as EV, non-EV, and best supportive care (BSC) groups, respectively. The median OS was 20, 15, and 7 months in the EV, non-EV, and BSC groups, respectively (p < 0.001). Patients with la/mUC who had a complete or partial response after EV treatment had a significantly prolonged OS compared with those with stable or progressive disease. Univariate analysis showed age, neutrophil-to-lymphocyte ratio (NLR), dysgeusia, and rash as independent predictors of OS improvement. NLR and dysgeusia were independent predictors of OS after EV in multivariate analysis. Patients without these factors had a significantly prolonged OS compared to those with both factors. In real-world practice, EV therapy is an effective treatment for patients with la/mUC after ICI treatment.

Utility and safety of robot-assisted radical cystectomy in older patients with bladder cancer.

Introduction: This study aimed to investigate the efficacy and safety of robot-assisted radical cystectomy (RARC) in older patients with bladder cancer (BCa).Material and methods: We reviewed the clinical and pathological records of 110 patients with BCa who underwent RARC at Gifu University Hospital between February 2019 and January 2023. Older patients were defined as those with BCa aged ≥ 75 years. The enrolled patients were divided into two groups: those aged < 75 years (Group I) and those aged ≥ 75 years (Group II). Oncological outcomes, including overall survival (OS) and recurrence-free survival (RFS), were the primary endpoints of the study; the secondary endpoints were the surgical and pathological outcomes.Results: A shorter console time, less blood loss, and reduced time to postoperative fluid and food intake in Group II may be attributed to the fact that more patients opted for ureterocutaneostomy in Group II than in Group I. In all patients, the three-year OS and RFS rates were 84.7% and 88.5%, respectively. There were no significant differences in OS or RFS between the two groups. (p = .403, p = .963, respectively).Conclusions: RARC appears to be a safe and useful treatment option for older patients with BCa.

Perilesional Targeted Biopsy Combined with MRI-TRUS Image Fusion-Guided Targeted Prostate Biopsy: An Analysis According to PI-RADS Scores.

A prostate-targeted biopsy (TB) core is usually collected from a site where magnetic resonance imaging (MRI) indicates possible cancer. However, the extent of the lesion is difficult to accurately predict using MRI or TB alone. Therefore, we performed several biopsies around the TB site (perilesional [p] TB) and analyzed the association between the positive cores obtained using TB and pTB and the Prostate Imaging Reporting and Data System (PI-RADS) scores. This retrospective study included patients who underwent prostate biopsies. The extent of pTB was defined as the area within 10 mm of a TB site. A total of 162 eligible patients were enrolled. Prostate cancer (PCa) was diagnosed in 75.2% of patients undergoing TB, with a positivity rate of 50.7% for a PI-RADS score of 3, 95.8% for a PI-RADS score of 4, and 100% for a PI-RADS score of 5. Patients diagnosed with PCa according to both TB and pTB had significantly higher positivity rates for PI-RADS scores of 4 and 5 than for a PI-RADS score of 3 (p < 0.0001 and p = 0.0009, respectively). Additional pTB may be performed in patients with PI-RADS ≥ 4 regions of interest for assessing PCa malignancy.

Efficacy and Safety of Neoadjuvant Luteinizing Hormone-Releasing Hormone Antagonist and Tegafur-Uracil Chemohormonal Therapy for High-Risk Prostate Cancer.

BACKGROUND: This retrospective single-center cohort study evaluated the efficacy and safety of a combination of neoadjuvant luteinizing hormone-releasing hormone (LHRH) antagonist and tegafur-uracil (UFT) therapy (NCHT) and investigated the medical records of patients with high-risk PCa who underwent robot-assisted radical prostatectomy (RARP). The therapy was followed by RARP for high-risk PCa. MATERIALS AND METHODS: The enrolled patients were divided into two groups: low-intermediate-risk PCa patients who underwent RARP without neoadjuvant therapy (non-high-risk) and those who underwent NCHT followed by RARP (high-risk group). This study enrolled 227 patients (126: non-high-risk and 101: high-risk group). Patients in the high-risk-group had high-grade cancer compared to those in the non-high-risk-group. RESULTS: At the median follow-up period of 12.0 months, there were no PCa deaths; two patients (0.9%) died of other causes. Twenty patients developed biochemical recurrence (BCR); the median time until BCR was 9.9 months after surgery. The 2-year biochemical recurrence-free survival rates were 94.2% and 91.1% in the non-high-risk and high-risk-group, respectively (p = 0.465). Grade ≥3 NCHT-related adverse events developed in nine patients (8.9%). CONCLUSIONS: This study indicates that combining neoadjuvant LHRH antagonists and UFT followed by RARP may improve oncological outcomes in patients with high-risk PCa.

Efficacy and Safety of Cabozantinib in Patients with Advanced or Metastatic Renal Cell Carcinoma: A Multicenter Retrospective Cohort Study.

A multicenter retrospective study was conducted to evaluate the efficacy and safety of cabozantinib in patients with advanced or metastatic renal cell carcinoma (mRCC). We enrolled 53 patients with mRCC who received cabozantinib at eight institutions in Japan. The primary endpoint was overall survival (OS). The secondary endpoints were objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS). In addition, we analyzed prognostic factors in patients with mRCC treated with cabozantinib. The median follow-up period was 8 months, and the median OS was 20.0 months. The ORR and DCR were 39.6% and 83.0%, respectively. The median PFS was 11.0 months. PFS was significantly shorter in patients previously treated with at least two tyrosine kinase inhibitors and in those with C-reactive protein (CRP) ≥ 1.27 mg/dL (p = 0.021 and p = 0.029, respectively). Adverse events of any grade and grades ≥3 occurred in 42 (79.2%) and 10 (18.9%) patients, respectively. Cabozantinib is a useful treatment option for patients with mRCC and may benefit from earlier use. In this study, CRP ≥ 1.27 mg/dL is a poor prognostic factor in patients treated with cabozantinib, and careful follow-up may be required in treating patients with high CRP.

Efficacy and Safety of the "Trisection Method" Training System for Robot-Assisted Radical Cystectomy at a Single Institution in Japan.

To maintain a surgeon's concentration, reduce fatigue, and train young surgeons, surgical procedures for bladder cancer are divided into the following parts: robot-assisted radical cystectomy (RARC), bowel reconstruction, and totally intracorporeal urinary diversion (ICUD) (RARC+ICUD). Each part is performed by a different surgeon (Trisection method). We retrospectively evaluated the efficacy and safety of this approach at a single institution in Japan. One hundred consecutive patients who underwent RARC+ICUD at Gifu University Hospital between November 2018 and August 2022 were included in this study. The patient background, surgical outcomes, and postoperative complications were compared between surgeries by first-, second-, and third-generation surgeons. The overall survival (OS) and recurrence-free survival (RFS) were compared between surgeries by each generation. Of the 100 patients, 19, 38, and 43 RARCs were performed by first-, second-, and third-generation surgeons, respectively. There were 35, 25, and 39 patients who underwent ileal conduit, neobladder, and ureterocutaneostomy, respectively. No significant differences were found among the patients respective to the type of ICUDs. Although the first-generation surgeon had a significantly shorter operative time with RARC, the surgical time for bowel reconstruction, length of hospital stays, and incidence of postoperative complications were not significantly different among the groups. Additionally, OS and RFS did not differ significantly among the generations. The "Trisection method" is an effective and safe concept with no difference in outcomes between the generations of surgeons.

The Impact of Neutrophil-to-Lymphocyte Ratio after Two Courses of Pembrolizumab for Oncological Outcomes in Patients with Metastatic Urothelial Carcinoma.

We focused on the therapeutic effect of pembrolizumab for metastatic urothelial carcinoma (mUC) and evaluated predictive factors for improving clinical outcomes. We conducted a retrospective multicenter cohort study of patients with mUC who received pembrolizumab. The endpoint was to evaluate the association between clinicopathological features and oncological outcomes. A total of 160 patients were enrolled in this study and were divided into two groups: the responder and the non-responder group, according to the best response. They were followed up for a median period of 10 months. The median overall (OS) and progression-free survival (PFS) in this study were 17 and 4 months, respectively. The responder group did not achieve median OS and it was 10 months in the non-responder group (p < 0.001). Similarly, the responder group did not achieve PFS, and it was 2 months in the non-responder group (p < 0.001). Regarding the neutrophil-to-lymphocyte ratio (NLR) after two courses of administration of pembrolizumab, patients with NLR < 3.24 had significantly better oncological outcomes than those with NLR ≥ 3.24. Multivariate analysis showed a significant association between NLR after two courses of pembrolizumab and OS. Therefore, the absolute value of NLR after two courses of pembrolizumab was a significant predictive factor for oncological outcomes.