Adrenalectomy for pheochromocytoma: Surgical outcomes and preoperative risk factors for hemodynamic instability.

BACKGROUND: Surgical resection for pheochromocytoma (PCC) is still challenging. This study assessed the perioperative outcomes of adrenalectomy for PCC and investigated the risk factors for intraoperative hemodynamic instability (HI). METHODS: This retrospective study included 571 patients with adrenal tumors who underwent adrenalectomy at Kobe University Hospital and other related hospitals between April 2008 and October 2023. The perioperative outcomes of laparoscopic adrenalectomy were compared between PCC (n = 92) and non-PCC (n = 464) groups. In addition, we investigated several potential risk factors for intraoperative HI in patients with PCC (n = 107; open, n = 11; laparoscopic, n = 92; robot-assisted, n = 4). RESULTS: While patients with PCC had a significantly larger amount of blood loss in comparison to those with non-PCC (mean, 70 and 30 mL, respectively; p = 0.004), no significant difference was observed in the rate of perioperative grade ≥III complications (1.1% vs. 0.6%; p = 0.516), and no perioperative mortality was observed in either group. A tumor size of ≥40 mm, with preoperative hypertension and urinary metanephrines at a level ≥3 times the upper limit of the normal value, were found to be significant predictors of HI, with odds ratios of 2.74 (p = 0.025), 3.91 (p = 0.005), and 3.83 (p = 0.004), respectively. CONCLUSIONS: Our data suggest that laparoscopic adrenalectomy for PCC may be as safe as that for other types of adrenal tumors and that large tumors and hormonally active disease may be risk factors for intraoperative HI. The optimal perioperative management for PCC with these risk factors should be established.

Prognostic outcomes in patients with metastatic renal cell carcinoma receiving second-line treatment with tyrosine kinase inhibitor following first-line immune-oncology combination therapy.

OBJECTIVES: This study aimed to assess the prognostic outcomes in mRCC patients receiving second-line TKI following first-line IO combination therapy. METHODS: This study retrospectively included 243 mRCC patients receiving second-line TKI after first-line IO combination therapy: nivolumab plus ipilimumab (n = 189, IO-IO group) and either pembrolizumab plus axitinib or avelumab plus axitinib (n = 54, IO-TKI group). Oncological outcomes between the two groups were compared, and prognostication systems were developed for these patients. RESULTS: In the IO-IO and IO-TKI groups, the objective response rates to second-line TKI were 34.4% and 25.9% (p = 0.26), the median PFS periods were 9.7 and 7.1 months (p = 0.79), and the median OS periods after the introduction of second-line TKI were 23.1 and 33.5 months (p = 0.93), respectively. Among the several factors examined, non-CCRCC, high CRP, and low albumin levels were identified as independent predictors of both poor PFS and OS by multivariate analyses. It was possible to precisely classify the patients into 3 risk groups regarding both PFS and OS according to the positive numbers of the independent prognostic factors. Furthermore, the c-indices of this study were superior to those of previous systems as follows: 0.75, 0.64, and 0.61 for PFS prediction and 0.76, 0.70, and 0.65 for OS prediction by the present, IMDC, and MSKCC systems, respectively. CONCLUSIONS: There were no significant differences in the prognostic outcomes after introducing second-line TKI between the IO-IO and IO-TKI groups, and the histopathology, CRP and albumin levels had independent impacts on the prognosis in mRCC patients receiving second-line TKI, irrespective of first-line IO combination therapies.

Treatment of Osteoporosis in Men on Androgen Deprivation Therapy in Japan.

Background and Objectives: Androgen deprivation therapy (ADT) for prostate cancer has greatly improved treatment outcomes. As patient survival rates have increased, reports of decreased bone density and increased bone fractures as side effects of ADT have emerged. The prevalence of osteoporosis in Japanese men was 4.6%. The purpose of this study was to evaluate the effect of osteoporosis treatment in prostate cancer patients who underwent ADT in Japan. Materials and Methods: The subjects were 33 male patients who had undergone ADT for prostate cancer, who were noted to have decreased bone density. Mean age was 76.2 ± 7.7 years (64-87). Medications included vitamin D in one case, bisphosphonates (BP) in 27 cases, and denosumab in five cases. The evaluation method examined the rate of change in bone mineral density (BMD) before osteoporosis treatment and 1 year after. For comparison, a group without osteoporosis treatment intervention (n = 33) was selected, and matched for prostate cancer treatment and age. The rate of change in trabecular bone score (TBS) was also calculated. Results: The percentage changes in BMD before and 1 year after treatment were as follows: lumbar spine, 7.1 ± 5.8% in the treatment group versus -3.9 ± 4.1% in the no treatment group; femoral neck, 5.5 ± 6.2% in the treatment group versus -0.9 ± 3.9% in the no treatment group; total femur, 6.6 ± 6.4% in the treatment group versus the no treatment group which was -1.7 ± 3.2%. In all cases, there was a clear significant difference (p < 0.01). The percent change in TBS was further calculated in the same manner. There was no significant difference between the two groups: +1.7 ± 3.8% in the treated group versus +0.3 ± 4.1% in the untreated group. Conclusions: Osteoporosis treatment in Japanese patients with prostate cancer on ADT therapy was found to significantly increase BMD compared to the untreated group. BP and denosumab were found to be very effective in increasing BMD.

Real-world analysis of metastatic prostate cancer demonstrates increased frequency of PSA-imaging discordance with visceral metastases and upfront ARAT/docetaxel therapy.

BACKGROUND: The objective of this study was to evaluate the background and treatment course of patients with metastatic prostate cancer (PC), with a particular focus on radiographic progression in the absence of prostate-specific antigen (PSA) progression. METHODS: The study population consisted of 229 patients with metastatic hormone-sensitive PC (HSPC), who received prostate biopsy and androgen deprivation therapy at Kobe University Hospital between January 2008 and June 2022. Clinical characteristics were retrospectively evaluated using medical records. PSA progression-free status was defined as ≤1.05 times greater than that from 3 months before. Multivariate analyses were performed using the Cox proportional hazards regression model to identify parameters associated with time to progression on imaging without PSA elevation. RESULTS: A total of 227 patients with metastatic HSPC without neuroendocrine PC were identified. The median follow-up period was 38.0 months, with a median overall survival of 94.9 months. Six patients exhibited disease progression on imaging without PSA elevation during HSPC treatment, three during first-line castration-resistant PC (CRPC) treatment, and two during late-line CRPC treatment. The rate of disease progression without PSA elevation at 3 years after treatment initiation was 7.4%. Multivariate analysis revealed that organ metastases and upfront treatment with docetaxel or androgen receptor axis-targeted therapy were independent prognostic factors for imaging progression without PSA elevation. CONCLUSIONS: Disease progression on imaging without PSA elevation occurred not only during HSPC treatment and first-line CRPC treatment, but also during late-line CRPC treatment. Patients with visceral metastases or those treated with upfront androgen receptor axis-targeted or docetaxel may be more prone to such progression.

Treatment outcome after sequential chemotherapy with cisplatin-etoposide, amrubicin and nogitecan in patients with treatment-related pure small-cell neuroendocrine prostate cancer.

OBJECTIVE: This study retrospectively reviewed the clinical characteristics and treatment outcomes of patients with histologically diagnosed treatment-related pure small-cell neuroendocrine prostate cancer. METHODS: We retrospectively evaluated data for 13 patients with treatment-related neuroendocrine prostate cancer who were diagnosed between May 2015 and February 2022. Standardized systemic therapies of etoposide plus cisplatin (or carboplatin), amrubicin and nogitecan were selected as sequential treatments. Cancer-specific survival and progression-free survival were evaluated as the primary endpoint. The Cox proportional hazards model was used to evaluate the relationships between treatment regimens, clinical variables, cancer-specific survival and progression-free survival. RESULTS: The median cancer-specific survival after diagnosis for all patients was 22.4 months (range 1.3-33.4 months). The median progression-free survival was 9.3 months after first-line etoposide plus cisplatin (or carboplatin) treatment (n = 13); 4.2 months after second-line amrubicin treatment (n = 4); and >15 months after third-line nogitecan treatment (n = 2). The median progression-free survival after first-line chemotherapy of the liver metastasis (-) group was 10.2 months, and that of the (+) group was 5.3 months (P = 0.015, hazard ratio = 11.6, 95% confidence interval = 1.01 - 133.7). No clinicopathological parameters were identified as significant independent predictors of cancer-specific survival in univariate analysis. CONCLUSION: Sequential chemotherapy with etoposide plus cisplatin (or carboplatin), amrubicin and nogitecan may be helpful for patients with treatment-related pure small-cell neuroendocrine prostate cancer. Early biopsy of metastases and initiation of effective therapy is essential for patients with progressive castration-resistant prostate cancer and low prostate-specific antigen.

Avelumab plus Axitinib for the Treatment of Patients with End-Stage Renal Disease Undergoing Dialysis: A Retrospective Case Series and Literature Review.

Combination therapies of an immune checkpoint inhibitor and a molecular targeted agent are widely accepted as an appropriate initial systemic therapy for metastatic renal cell carcinoma (RCC), but there is little published evidence regarding the efficacy of this approach in patients with end-stage renal disease (ESRD). Here, we report three patients who were undergoing hemodialysis for ESRD whose metastatic RCC was successfully treated using avelumab plus axitinib. The patients were a 67-year-old man with swollen lymph nodes, a 65-year-old man with pleural dissemination, and a 71-year-old man with lung nodules and an infra-diaphragmatic nodule. They were administered a combination of avelumab plus axitinib as their initial systemic therapy following definitive surgical therapy. The best response of three patients was graded as partial response. No severe adverse events were identified. This is the first report of the use of combination therapy consisting of avelumab plus axitinib in patients with ESRD undergoing hemodialysis. We found that this combination was useful in such patients.

Impact of cytoreductive nephrectomy prior to combination therapy of ipilimumab plus nivolumab in metastatic renal cell carcinoma.

OBJECTIVES: The efficacy of cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC) treated with immune checkpoint inhibitors (ICIs) has been suggested in the real-world setting. We retrospectively examined the efficacy of CN prior to nivolumab plus ipilimumab systemic therapy for synchronous mRCC. METHODS: Synchronous mRCC patients who received nivolumab plus ipilimumab at Kobe University Hospital or five affiliated hospitals between October 2018 and December 2021 were included in this study. We compared the outcomes of objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) between patients with CN prior to systemic therapy and without CN. In addition, patients were 1:1 matched by propensity scores accounting for factors associated with treatment assignment. RESULTS: Twenty-one patients received CN prior to nivolumab plus ipilimumab (Prior CN) and 33 received nivolumab plus ipilimumab alone (Without CN). PFS of the Prior CN group was 10.8 months (95%CI 5.5-NR) and 3.4 months (95%CI 2.0-5.9) for the Without CN group (p = 0.0158). OS of Prior CN was 38.4 months (95%CI NR-NR) and 12.6 months (95%CI 4.2-30.8) for Without CN (p = 0.0024). Univariate and multivariate analyses identified prior CN as a significant prognostic indicator for PFS and OS. Moreover, propensity score matching analysis showed significant improvements in PFS and OS in Prior CN. CONCLUSIONS: Patients who underwent CN prior to nivolumab plus ipilimumab systemic therapy for synchronous mRCC had a better prognosis than patients treated with nivolumab plus ipilimumab alone. These results suggest the efficacy of prior CN for synchronous mRCC with ICI combination therapy.

Efficacy and safety of pembrolizumab and axitinib as first-line treatment for patients with advanced renal cell carcinoma: Real-world experience in Japan.

OBJECTIVES: The objective of this study was to assess the clinical outcomes following combined treatment with pembrolizumab and axitinib as first-line therapy for patients with advanced RCC. METHODS: This study retrospectively included 47 consecutive Japanese patients who were diagnosed with advanced RCC and subsequently received pembrolizumab and axitinib between February 2020 and January 2022. Efficacy and safety of this combined therapy in these patients were comprehensively investigated. RESULTS: The 47 included patients were classified into the following 3 groups by the IMDC system: favorable, 7 (14.9%); intermediate, 24 (51.1%) and poor, 16 (34.0%). Responses to this combined therapy in the 47 patients were as follows: CR, 8 (17.0%); PR, 20 (42.6%); SD, 16 (34.0%) and PD, 3 (6.4%); thus, the ORR was 59.6%. During the observation period, disease progression and death occurred in 19 (40.4%) and 9 (19.1%) patients, respectively, and the median PFS and OS were 18 months and not reached, respectively. Univariate analyses identified the following significant predictors for poor prognostic outcomes: lack of nephrectomy, liver metastasis, bone metastasis, elevated CRP and IMDC poor risk for PFS; and lack of nephrectomy, non-CCC and elevated CRP for OS. AEs and those corresponding to grade ≥ 3 occurred in all (100%) and 30 (63.8%) patients, respectively. CONCLUSIONS: To our knowledge, this is the first study focusing on real-world outcomes following pembrolizumab and axitinib for treatment-naïve advanced Japanese RCC patients, which showed the efficacy and safety of this combined therapy being similar or even superior to those in clinical trial.

The poor antitumor effect of pembrolizumab in advanced upper urothelial carcinoma with renal parenchymal invasion.

OBJECTIVES: We investigated poor prognosticators in advanced or unresectable urothelial carcinoma, focusing on renal parenchymal invasion (RPI). METHODS: This study included 48 bladder cancer (BC) and 67 upper tract urothelial carcinoma (UTUC) patients treated with pembrolizumab from December 2017 to September 2022 at Kobe University Hospital. Medical records were retrospectively reviewed for clinical characteristics, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Multivariate analyses were performed using the Cox proportional hazard regression model to identify parameters associated with either PFS or OS. RESULTS: Of 67 UTUC patients, 23 had RPI and 41 patients did not, while 3 cases could not be evaluated. Patients with RPI were predominantly elderly and had liver metastases. ORR for patients with RPI was 8.7%, while it was 19.5% for those without RPI. PFS was significantly shorter for patients with RPI compared with those without RPI. Patients with RPI had significantly shorter OS than those without RPI. On multivariate analysis, performance status (PS) ≥ 2, neutrophil-lymphocyte ratio (NLR) ≥ 3, C-reactive protein ≥0.3 mg/dL and RPI were independent prognostic factors for PFS. PS ≥ 2, NLR ≥ 3, visceral metastasis and RPI were independent prognostic factors for OS. UTUC patient OS was significantly shorter than BC patient OS, while no significant difference in PFS or OS was observed between BC patients and UTUC patients without RPI. CONCLUSIONS: RPI was a poor prognostic factor in advanced urothelial carcinoma treated with pembrolizumab, possibly resulting in a poorer prognosis for UTUC compared with BC.

Treatment outcomes of molecular targeted therapy following nivolumab in metastatic renal cell carcinoma.

OBJECTIVE: The purpose of this study was to assess the therapeutic efficacy of molecular targeted therapies following nivolumab in metastatic renal cell carcinoma and to examine the relationship between therapeutic efficacy and the specific molecular targeted therapy used. METHODS: We retrospectively reviewed the medical records of 115 metastatic renal cell carcinoma patients who were treated with nivolumab at our institution and five affiliated hospitals. Among them, 52 patients who received subsequent molecular targeted therapy following nivolumab were selected to survey treatment outcomes. Progression-free survival and overall survival were estimated with Kaplan-Meier curves, and differences were analyzed by the log-rank test. RESULTS: Among the 52 eligible patients, 40 (76.9%) were treated with tyrosine kinase inhibitors and 12 (23.1%) were treated with mammalian target of rapamycin inhibitor. The median time to treatment failure and progression-free survival of subsequent molecular targeted therapy were 5.6 and 8.0 months, respectively. The median overall survival from the initiation of first-line therapy was not reached. The disease control rate of subsequent molecular targeted therapy was 69.2% (partial response: 25.0%, stable disease: 44.2%). The median progression-free survival of subsequent tyrosine kinase inhibitor and mammalian target of rapamycin inhibitor were 9.2 and 8.0 months, respectively (P = 0.37). The progression-free survival of patients whose best response to prior nivolumab was either progressive disease or stable disease/partial response were 6.3 and 11.3 months, respectively (P = 0.36). CONCLUSIONS: Molecular targeted therapies following nivolumab had comparatively better therapeutic efficacy, which was confirmed regardless of the type of molecular targeted agent used.

Comparison of robot-assisted partial nephrectomy for complex (RENAL scores ≥10) and non-complex renal tumors: A single-center experience.

OBJECTIVES: To compare functional and surgical outcomes of robot-assisted partial nephrectomy for complex tumors with RENAL scores ≥10 and non-complex tumors at a single academic institution. METHODS: We retrospectively analyzed the data of all patients who underwent robot-assisted partial nephrectomy at Kobe University Hospital (Kobe, Hyogo, Japan) from 2011 to 2020. Functional and surgical outcomes for complex tumors (RENAL score ≥10) were compared with those of patients with non-complex tumors (RENAL <10). Outcomes analyzed included blood loss, warm ischemia time, console time, perioperative complications, and preoperative and postoperative renal function. RESULTS: A total of 348 patients were included in our present study, with a median follow-up time of 35.1 months. Of these, 299 patients (85.9%) had non-complex tumors and 49 patients (14.1%) had complex tumors. Warm ischemia time and console time were significantly longer in the complex tumors group. Major perioperative complications (Clavien-Dindo classification system ≥3) were significantly more frequent in the complex tumors group than the non-complex tumor group (16.3% vs 5.7%, P = 0.018). Postoperative preservation of estimated glomerular filtration rate and percentage of chronic kidney disease upstage by 1 year were significantly inferior in the complex tumors group. The positive surgical margin rate was 0% and 0.3% in the complex and non-complex tumor groups, respectively. There were no significant differences in recurrence-free survival between the two groups (P = 0.11). CONCLUSIONS: Robot-assisted partial nephrectomy for complex renal tumors is safe, with no difference in oncological outcomes, although more postoperative complications and decreased renal function can be observed than non-complex tumors.

Diagnostic and therapeutic value of pelvic lymph node dissection in the fossa of Marcille in patients with clinically localized high-risk prostate cancer: Histopathological and molecular analyses.

BACKGROUND: The optimal extent of lymph node dissection in radical prostatectomy has not been determined. Lymph nodes in the fossa of Marcille, which is an important pelvic lymphatic pathway and candidate for additional dissection, have not been evaluated at the molecular level. Here, we assessed by molecular analysis the presence of occult positive lymph nodes in the fossa of Marcille in patients with clinically localized high-risk prostate cancer. METHODS: Fifty-two patients with clinically localized high-risk prostate cancer underwent pelvic lymph node dissection accompanied by robot-assisted radical prostatectomy. All nodal packets were dissected separately and grouped into right and left obturator, external and internal iliac regions (including common iliac region to ureter crossing), and fossa of Marcille. All lymph nodes were bisected and evaluated by histopathological or molecular analysis using a quantitative reverse transcription-polymerase chain reaction. The number of positive lymph nodes in the fossa of Marcille and the difference in detection rate were investigated using histopathological and molecular analyses. Perioperative complication rate and predictive factors for biochemical recurrence were evaluated. RESULTS: In the molecular analysis, there were seven positive lymph nodes in the fossa of Marcille in three patients, which were coexistent with positive nodes in other regions. The detection rate of positive lymph nodes was significantly higher using molecular than histopathological analysis (P < .01). Perioperative complication rate within 90 days after the operation was 25.0% and no Clavien-Dindo grade ≥3 complication was confirmed. Detection of metastasis by histopathological and molecular analysis was a significant factor related to biochemical recurrence in the Cox proportional hazards regression model. CONCLUSIONS: No case of positive lymph nodes in the fossa of Marcille that had skipped over other regions was confirmed. Additional lymph node dissection of fossa of Marcille did not lead to complete resection of molecularly positive lymph nodes.

Application of hyaluronic acid/carboxymethyl cellulose membrane for early continence after nerve-sparing robot-assisted radical prostatectomy.

BACKGROUND: To assess whether application of a hyaluronic acid-carboxymethyl cellulose membrane (HA/CMC) to the prostate bed and neurovascular plate facilitated early return of continence after nerve-sparing robot-assisted radical prostatectomy (RARP). METHODS: The subjects were 183 consecutive patients with organ-confined prostate cancer who underwent unilateral or bilateral nerve-sparing RARP. After vesicourethral anastomosis, HA/CMC was placed to cover Denonvilliers' fascia (behind the anastomotic suture) and the preserved neurovascular plate. The time until complete continence after RARP and perioperative complications were compared between patients with or without HA/CMC. RESULTS: HA/CMC was applied in 13/46 patients (28.3%) receiving bilateral nerve-sparing surgery and 40/137 patients (29.2%) receiving unilateral nerve-sparing surgery. After bilateral nerve-sparing RARP, the median time until continence was significantly shorter in patients with HA/CMC than in those without HA/CMC (3.2 vs. 9.3 months, respectively, p < 0.01). After unilateral nerve-sparing RARP, the median time until continence was also significantly shorter in patients with HA/CMC than in those without HA/CMC (3.2 vs. 12.0 months, respectively, p < 0.01). Multivariate Cox proportional hazards regression analysis showed that an age < 70 years (hazard ratio [HR]: 1.74, 95% confidence interval [CI]: 1.12-2.80), institutional caseload > 200, (HR: 1.64, 95%CI: 1.10-2.47), and use of HA/CMC (HR: 1.84, 95%CI: 1.22-2.76) were independent predictors of early postoperative continence. Complication rates, including urinary leakage, did not differ significantly between patients with or without HA/CMC. CONCLUSION: Application of HA/CMC to the prostate bed and neurovascular plate resulted in significantly faster postoperative return of continence after both unilateral and bilateral nerve-sparing RARP.

Presurgical pazopanib for renal cell carcinoma with inferior vena caval thrombus: a single-institution study.

The aim of this study was to investigate the clinical benefit of presurgical therapy with pazopanib in renal cell carcinoma (RCC) patients with a tumor thrombus extending to a high level in the vena cava. A retrospective review was performed for seven consecutive patients with RCC and tumor thrombus involving the vena cava above the hepatic vein (level 3-4, Mayo Clinic classification) treated with pazopanib without initial cytoreductive nephrectomy at our institution. The effect of pazopanib was assessed in terms of the primary site response, thrombus diameter, and height (before and after treatment) on computed tomography or MRI. The tumor thrombus level before the induction of pazopanib was 3 in one patient and 4 in the remaining six patients. After pazopanib, shrinkage of the primary site and thrombus diameter and length were observed in all patients except one (with a rhabdoid tumor). The mean decreases of primary tumor diameter, tumor thrombus diameter, and length were 14, 9, and 31 mm, respectively. The tumor thrombus level decreased in three (43%) patients and remained stable in the remaining patient. Our findings suggest that presurgical treatment with pazopanib may shrink the tumor thrombus and decrease the surgical invasiveness in RCC patients with a high-level tumor thrombus.

Therapeutic outcome of combination therapy using immune-checkpoint inhibitors and tyrosine kinase inhibitors for metastatic non-clear-cell renal cell carcinoma.

INTRODUCTION: We aimed to clarify the therapeutic outcome of combination therapy using immune-checkpoint inhibitors (ICIs) and/or tyrosine kinase inhibitors (TKIs) for meta-static non-clear-cell renal cell carcinoma (nccRCC). METHODS: We have been retrospectively investigating the therapeutic efficacy and prognosis in 36 patients with metastatic nccRCC undergoing combination therapy using two ICIs, ipilimumab plus nivolumab (ICI-ICI), and ICI plus TKI (ICI-TKI), at Kobe University and affiliated institutions since 2018. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and adverse event (AE) were compared. RESULTS: The first-line regimen was ICI-ICI in 26 cases and ICI-TKI in 10 cases. The ORRs in the ICI-ICI and ICI-TKI groups were 34.6 and 30.0%, respectively (p=0.9433). The 50% PFS for the ICI-TKI group was 9.7 months, significantly longer than that for the ICI-ICI group (4.6 months, p=0.0499), and there was no significant difference in OS between groups (p=0.3984). There was no significant difference in the occurrence rate of AE for below grade 2 (p=0.8535), nor above grade 3 (p=0.3786) between the ICI-ICI and ICI-TKI groups. CONCLUSIONS: From our analysis of real-world data, a better outcome of PFS was expected in the ICI-TKI group compared with that in the ICI-ICI group, while there was no significant difference in OS or ORR.

Clinical Outcomes and Risk Stratification in Patients With Metastatic Hormone-Sensitive Prostate Cancer Treated With New-Generation Androgen Receptor Signaling Inhibitors.

BACKGROUND: Optimal drug selection for metastatic hormone-sensitive prostate cancer (mHSPC) remains unclear. We therefore assessed the clinical outcomes of mHSPC treated with new-generation androgen receptor pathway inhibitors (ARSIs) and identified risk factors associated with the prognosis of mHSPC. METHODS: We retrospectively reviewed 324 patients with mHSPC who were treated with ARSIs, including abiraterone acetate, enzalutamide, and apalutamide, between January 2018 and December 2022. In addition to assessing the prostate-specific antigen (PSA) response and overall survival (OS) during ARSI treatment, we investigated several potential risk factors for a poor OS in patients with mHSPC. RESULTS: Patients with a ≥ 90% PSA reduction (hazard ratio [HR]: 0.24, 95% confidence interval [CI], 0.10-0.58; P = .002) and those whose PSA declined to ≤ 0.2 ng/mL (HR: 0.22, 95% CI, 0.08-0.63; P = .005) showed significantly better OS than other patients. Gleason grade group 5 (GG5), presence of liver metastasis, and an LDH ≥ 250 U/L were identified as prognostic factors significantly associated with a poor OS, with HRs of 2.31 (95% CI, 1.02-5.20; P = .044), 7.87 (95% CI, 2.61-23.8; P < .001) and 3.21 (95% CI, 1.43-7.23; P = .005). CONCLUSION: We identified GG5, the presence of liver metastasis, and elevated LDH at the diagnosis as significant factors predicting the OS of mHSPC, but the choice of ARSIs did not affect the prognosis. The potential prognostic impact of these markers requires further investigation.

Comparison of Cabozantinib and Axitinib as Second-line Therapy After Nivolumab Plus Ipilimumab in Patients With Metastatic Clear Cell Renal Cell Carcinoma: A Comparative Analysis of Retrospective Real-world Data.

BACKGROUND: To date, no studies have compared the treatment outcomes of second-line therapies in patients with metastatic clear cell renal cell carcinoma (ccRCC). This study retrospectively evaluated the efficacy of cabozantinib and axitinib as second-line treatments in patients with metastatic ccRCC who previously received immune-oncology combination therapy. PATIENTS AND METHODS: Patients with metastatic ccRCC treated with cabozantinib and axitinib as second-line therapy after nivolumab-ipilimumab treatment were identified among 243 patients with RCC treated between August 1, 2018 and January 31, 2022 at 34 institutions belonging to the Japanese Urological Oncology Group. Patients were assessed for treatment outcomes, including progression-free survival (PFS), overall survival, objective response rate (ORR), and incidence rate of treatment-related adverse events (AEs). RESULTS: Forty-eight patients treated with cabozantinib and 60 treated with axitinib as second-line therapy after nivolumab-ipilimumab treatment for metastatic ccRCC were identified. The median PFS (95% confidence interval) was 11.0 months (9.0-16.0) with cabozantinib and 9.5 months (6.0-13.0) with axitinib. The ORRs were 37.5% (cabozantinib) and 38.3% (axitinib). The rates of any-grade AEs and grade ≥3 AEs were 79.2% (cabozantinib) versus 63.3% (axitinib; P = .091) and 35.4% (cabozantinib) versus 23.3% (axitinib; P = .202), respectively. In the poor-risk group, PFS was longer in the cabozantinib group than in the axitinib group (P = .033). CONCLUSION: The efficacy and safety of cabozantinib and axitinib were comparable. In the poor-risk group, cabozantinib was more effective than axitinib. These findings provide valuable insights into the selection of second-line treatment options after nivolumab-ipilimumab treatment in patients with metastatic ccRCC.

Prognostic Value of Serum Soluble PD-L1 in Metastatic Renal Cell Carcinoma Patients Treated With Nivolumab.

BACKGROUND/AIM: Increasing availability of effective treatment options for metastatic renal cell carcinoma (mRCC) has highlighted the importance of identifying predictors of treatment response. Although PD-L1 expression in renal cancer has been reported as a predictor of treatment response and prognosis, its assessment by immunohistochemistry is invasive and difficult to perform repeatedly. Soluble PD-L1 (sPD-L1) has recently been proposed as a predictive biomarker for several tumour types. Therefore, we evaluated sPD-L1 levels in patients with mRCC treated with nivolumab and investigated its association with treatment response. PATIENTS AND METHODS: We performed a prospective single-arm study in patients with mRCC treated with nivolumab as second line or later therapy. We measured serum sPD-L1 before and during treatment, classified patients based on baseline values (sPDL1 ≥0.23 ng/ml vs. <0.23 ng/ml) and compared outcomes between the two groups. RESULTS: A total of 43 patients with mRCC were included in this study, with 17 (39.5%) classified as low sPD-L1 and 26 (60.5%) as high sPD-L1. The International Metastatic RCC Database Consortium risk score was significantly poorer in the high sPD-L1 group. The objective response rate was significantly higher (41.2% vs. 7.7%) and overall survival significantly longer (p=0.0323) in the low group compared to the high group. There were no significant differences in progression-free survival between the two groups. CONCLUSION: Our study findings indicate that sPD-L1 might be a predictor of treatment response to nivolumab in patients with mRCC.

Robot-assisted laparoscopic pyeloplasty in the management of lower pole ureteropelvic junction obstruction in a patient with an incomplete duplicated collecting system.

Introduction: The performance of robot-assisted laparoscopic pyeloplasty has recently been increasing in frequency. However, patients with duplicated renal pelvises and ureters can present challenges. Case presentation: A 71-year-old woman presented with flank pain and was diagnosed with ureteropelvic junction obstruction with an incomplete duplicated collecting system. Preoperative imaging did not reveal the details of the stenosis. Therefore, three reconstructive procedures were prepared: The Anderson-Hynes procedure, end-to-side pyeloureterostomy, and upper pole ureter to lower pole pyeloplasty with the Anderson-Hynes procedure for the lower pole. These procedures were determined by the length of the intact ureter and the presence of crossed vessels. During the surgery, the crossing vein was severed, allowing successful reconstruction with Anderson-Hynes anastomosis. Conclusion: Preoperative evaluation and preparation of multiple surgical techniques are crucial in robot-assisted laparoscopic pyeloplasty for incomplete duplicated collecting systems.

An oral cancer vaccine using Bifidobacterium vector augments combination of anti-PD-1 and anti-CTLA-4 antibodies in mouse renal cell carcinoma model.

Recently, immune checkpoint inhibitor (ICI) based combination therapies, including anti-PD-1 antibody, nivolumab with anti-CTLA-4 antibody, and ipilimumab have become the primary treatment option for metastatic or unresectable renal cell carcinoma (RCC). However, despite the combination of two ICIs, 60-70% of patients are still resistant to first-line cancer immunotherapy. In the present study, undertook combination immunotherapy for RCC using an oral cancer vaccine (Bifidobacterium longum displaying WT1 tumor associated antigen (B. longum 420)) with anti-PD-1 and anti-CTLA-4 antibodies in a mouse syngeneic model of RCC to explore possible synergistic effects. We found that B. longum 420 significantly improved the survival of mice bearing RCC tumors treated by anti-PD-1 and anti-CTLA-4 antibodies compared to the mice treated by the antibodies alone. This result suggests that B. longum 420 oral cancer vaccine as an adjunct to ICIs could provide a novel treatment option for RCC patients. Our microbiome analysis revealed that the proportion of Lactobacilli was significantly increased by B. longum 420. Although the detailed mechanism of action is unknown, it is possible that microbiome alteration by B. longum 420 enhances the efficacy of the ICIs.