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.

Biochemical recurrence after chemohormonal therapy followed by robot-assisted radical prostatectomy in very-high-risk prostate cancer patients.

Robot-assisted radical prostatectomy (RARP) has become one of the standard radical treatments for prostate cancer (PCa). A retrospective single-center cohort study was conducted on patients with PCa who underwent RARP at Gifu University Hospital between September 2017 and September 2022. In this study, patients were classified into three groups based on the National Comprehensive Cancer Network risk classification: low/intermediate-risk, high-risk, and very-high-risk groups. Patients with high- and very-high-risk PCa who were registered in the study received neoadjuvant chemohormonal therapy prior to RARP. Biochemical recurrence-free survival (BRFS) after RARP in patients with PCa was the primary endpoint of this study. The secondary endpoint was the relationship between biochemical recurrence (BCR) and clinical covariates. We enrolled 230 patients with PCa in our study, with a median follow-up of 17.0 months. When the time of follow-up was over, 19 patients (8.3%) had BCR, and the 2 years BRFS rate for the enrolled patients was 90.9%. Although there was no significant difference in BRFS between the low- and intermediate-risk group and the high/very-high-risk group, the 2 years BRFS rate was 100% in the high-risk group and 68.3% in the very-high-risk group (P = 0.0029). Multivariate analysis showed that positive surgical margins were a significant predictor of BCR in patients with PCa treated with RARP. Multimodal therapies may be necessary to improve the BCR in patients with very-high-risk PCa.

Case of extragonadal germ cell tumor mimicking left adrenal tumor.

A 30-year-old man presented to his previous physician with left abdominal pain. Computed tomography revealed a left retroperitoneal mass with calcification, measuring 15 × 9 × 6 cm, and the patient was referred to our hospital for further examination. Based on the endocrinologic examination and magnetic resonance imaging results, the patient was diagnosed with a nonfunctional left adrenal tumor, and laparoscopic left adrenalectomy was performed. Histopathology revealed well-defined boundaries between the tumor and the left adrenal gland, and the tumor was diagnosed as a non-seminoma consisting mainly of an immature teratoma with germ cell neoplasm in situ.

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.

The Efficacy and Safety of Immune Checkpoint Inhibitor and Tyrosine Kinase Inhibitor Combination Therapy for Advanced or Metastatic Renal Cell Carcinoma: A Multicenter Retrospective Real-World Cohort Study.

We evaluated the efficacy and safety of combination therapy with immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKI) as first-line therapy for patients diagnosed as having advanced or metastatic renal cell carcinoma (mRCC). We enrolled 51 patients to receive ICI+TKI therapy for mRCC at 9 Japanese institutions. The overall survival (OS) of the patients treated with ICI+TKI was the primary endpoint., and the secondary endpoints were progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). Furthermore, we analyzed the clinical prognostic and predictive factors in patients with mRCC treated with ICI+TKI therapy. Seven months was the median follow-up period. The OS rates at 6, 12, and 18 months were 93.1, 82.5, and 68.8%, respectively. The median PFS for patients who received ICI+TKI was 19.0 months, ORR was 68.6%, and DCR was 88.2%. ICI+TKI-related adverse events occurred in 43 patients (84.3%) with any grade and in 22 patients (43.1%) with grade ≥3. Treatment selection with poor prognostic factors may be prudent, even though ICI+TKI is an efficacious and safe first-line treatment in patients with mRCC.

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.

Oncological Outcomes in Patients with Metastatic Urothelial Carcinoma after Discontinuing Pembrolizumab as a Second-Line Treatment: A Retrospective Multicenter Real-World Cohort Study.

The treatment options are currently limited, and the oncological outcomes remain unclear, for patients with metastatic urothelial carcinoma (mUC) with or without third-line systemic therapy. We aimed to evaluate the oncological outcomes in real-world daily clinical practice after platinum-based chemotherapy followed by pembrolizumab for mUC. This retrospective, multicenter cohort study included patients with mUC who received second-line pembrolizumab in Japan. The patients were divided into the treatment group (those who received third-line treatment) and the BSC group (those who did not receive other treatments). The primary endpoint of this study was to evaluate the oncological outcomes. Of 126 patients enrolled in this study, 40 received third-line therapy. The median follow-up period was 8.0 months. The median overall survival (OS) times were nine months in the BSC group and 17 months in the treatment group (p < 0.001). The median progression-free survival (PFS) times were 4 months in the BSC group and 14 months in the treatment group (p < 0.001). In the multivariate analysis, performance status and liver metastasis were significantly associated with OS. Third-line therapy may have clinical potential advantages for improving the oncological outcomes in patients with mUC.