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.

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.

Bioabsorbable zinc alloys for use in urological surgery.

PURPOSE: Non-absorbable clips are widely used in urologic surgery and they may come in contact with an open urinary tract intraoperatively. As a result, stray clips in the urinary tract and associated intractable infections have been reported. We developed a bioabsorbable metal and evaluated whether it would dissolve if it strayed into the urinary tract. METHODS: We prepared four types of alloys mainly comprising zinc (Zn) with small amounts of magnesium (Mg) and strontium (Sr), and the biological effects, degradability, strength, and ductility were investigated. Each alloy was implanted in the bladder of five rats for 4, 8, and 12 weeks. The alloys were removed and evaluated for degradability, stone adhesion, and tissue changes. The Zn-Mg-Sr alloy had degradability and no stone adhesion in the rat experiments, and it was implanted in the bladders of five pigs for 24 weeks. The Mg and Zn levels in the blood were measured, and staple changes were confirmed by cystoscopy. RESULTS: Zn-Mg-Sr alloys showed the best degradability of 6.51% at 12 weeks. In pig experiments, the degradation rate was 3.72% at 24 weeks. None of the pigs had changes in the Zn or Mg concentrations in the blood. Overall, the bladder incision was healed and the gross pathology showed wound healing. CONCLUSIONS: The Zn-Mg-Sr alloys were safely used in animal experiments. Furthermore, the alloys are easy to process and can be formed into various shapes, such as staples, making them useful in robotic surgery.

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.

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.

Development of bioabsorbable zinc-magnesium alloy wire and validation of its application to urinary tract surgeries.

PURPOSE: Metallic medical devices are typically constructed from non-bioabsorbable metals that remains in the body and causes considerable complications. Particularly in the urinary tract, calculus, intractable infection, and misdiagnosis as calculus are often caused by non-bioabsorbable metals. Here, we developed a zinc-magnesium alloy as a new bioabsorbable metal and sought to evaluate the bioabsorbable behavior of zinc and zinc-magnesium alloy in a rat bladder implantation model. METHODS: We prepared zinc-magnesium alloy wires with various proportions of magnesium and investigated the strength, shape retention, formability, and absorbability of these novel materials. Then, we implanted zinc and zinc-magnesium alloy rings formed by the wires into rat bladder. Rats were euthanized at the end of the observation period, and the rings were removed for volume evaluation. Extracted bladder tissues were subjected to histological analysis. RESULTS: The strength of the zinc wire was enhanced by more than fourfold upon the addition of magnesium, without loss of ductility. Linear reduction of ring volume in urine was observed based on the concentration of magnesium within the ring. Nearly all rings were covered with a thin layer of calculus. Histological findings of the transected urinary bladder tissues did not differ among groups. CONCLUSIONS: Zinc-magnesium alloy is a promising candidate for use as a bioabsorbable medical device in the urinary tract.

Prognostic impact of bone metastatic volume beyond vertebrae and pelvis in patients with metastatic hormone-sensitive prostate cancer.

BACKGROUND: Although bone metastasis beyond the vertebrae and pelvis has been a key factor in prognostic models of metastatic hormone-sensitive prostate cancer (mHSPC), the clinical significance of it is still unclear. The present study evaluated the prognostic impact of the volume of bone metastasis beyond the vertebrae and pelvis on the outcomes of mHSPC and created an ideal risk classification based on it. METHODS: We retrospectively reviewed 197 patients with mHSPC who were treated with combined androgen blockade as the initial treatment between June 2003 and October 2019. We calculated the bone scan index (BSI), including the BSI beyond the vertebrae and pelvis (bBSI), using BONENAVI, and investigated the association between the BSI and the overall survival (OS) of mHSPC. RESULTS: According to the CHAARTED criteria, 91 and 106 patients were classified into the low- and high-volume groups, respectively. Of the 79 patients who did not have visceral metastasis in the high-volume group, those with a bBSI ≤ 0.27 (n = 16) showed a favorable OS, as did those in the low-volume group. The modified CHAARTED high-volume group (presence of visceral metastases or 4 bone lesions with a bBSI > 0.27) showed a significantly shorter OS than others, with a hazard ratio (HR) of 4.69 (p < 0.001), which was higher than that observed with the original CHAARTED criteria (HR = 4.33). CONCLUSIONS: Our data suggested that considering the volume of bone metastasis beyond the vertebrae and pelvis may help to improve the accuracy of risk classification. Further large-scale prospective studies are needed to validate our findings.

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.

External validation of nomograms for prediction of progression-free survival and liver toxicity in patients with advanced renal cell carcinoma treated with pazopanib.

BACKGROUND: Nomograms have been developed for the prediction of progression-free survival (PFS) and liver toxicity in patients with advanced renal cell carcinoma (RCC) who are treated with pazopanib. The objectives of this study were to review clinical outcomes, to perform an external validation of these nomograms and to develop a new nomogram in Japanese patients. METHODS: A retrospective chart review of 150 Japanese patients with advanced RCC who received pazopanib at Kobe University Hospital and affiliated hospitals from March 2014 to June 2017 was performed. We evaluated the clinical efficacy and safety of pazopanib using logistic regression analysis to analyze the prognostic factors for overall survival (OS) and PFS. For nomogram validation, concordance index (C-index) and calibration were used. RESULTS: The median PFS and OS in this study was 13.1 and 37.4 months, respectively. Multivariate analyses identified prognostic factors for OS (number of metastasis, white blood cell (WBC) count and lactate dehydrogenase) and PFS (number of metastasis, WBC count). The C-index of nomograms for 12-month PFS was 0.598. The C-index of nomograms for liver toxicity was 0.558. A new Nomogram for predicting 12-month PFS for patients who received pazopanib was developed and performed internal validation. The C-index of the nomogram was 0.768. CONCLUSION: The clinical effect and safety of pazopanib reported in this study was similar to previous studies. This study suggests careful application of nomograms to Japanese patients treated with pazopanib. We have developed a new nomogram for predicting 12-month PFS with pazopanib therapy from Japanese patients.

[Clinical Outcome of Laparoscopic Partial Nephrectomy].

The purpose of this study was to evaluate the safety and feasibility of laparoscopic partial nephrectomy with a small renal tumor. Between September 2004 and October 2014, 69 patients who underwent laparoscopic partial nephrectomy in Kansai Rosai Hospial were examined. The mean patient age was 60.3 years, and the mean tumor size was 24.5 mm. The mean estimated blood loss was 111 cc. The mean cold ischemic time was 59.7 minutes, and the mean warm ischemic time was 31.3 minutes. There were 5 complications : intraoperative ureteral injury, blood transfusion, postoperative perinephric hematoma, portsite bleeding, urinary fistula, respectively. All of the cases were cured with non-surgical treatment except ureteral injury which was repaired intraoperatively. The postoperative eGFR loss was 11%. At present, no patients have developed local recurrence or distant metastasis. The initial outcome of laparoscopic partial nephrectomy in our hospital was satisfactory in terms of safety, renal function and cancer control.

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.

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.

The impact of primary region resection on the therapeutic outcome of combination regimens for metastatic renal cell carcinoma.

The present study aimed to clarify the relationship between the therapeutic outcome of combination regimens, including immune checkpoint inhibitors (ICIs) and/or tyrosine kinase inhibitors (TKIs), and cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC). The present study retrospectively assessed the association between treatment efficacy and prognosis with or without CN, and the timing of CN in 151 patients treated with combination regimens for mRCC who were categorized as intermediate/poor risk. The first-line regimens included the ICI-ICI and ICI-TKI regimens in 98 and 53 cases, respectively. In patients with recurrence after radical surgery (n=66), the 50% PFS times of the ICI-ICI and the ICI-TKI groups were 33.6 months and not reached (NR) (P=0.4032), respectively, and the 50% OS times were 53.7 months and NR (P=0.6886), respectively. Among the 38 patients with metastasis from the initial diagnosis who underwent upfront CN, the 50% PFS times of the ICI-ICI and the ICI-TKI groups were 10.5 and 8.2 months (P=0.5806), respectively, and the 50% OS times were NR and 15.8 months (P=0.0587), respectively. Among the 51 patients who did not receive upfront CN, the 50% PFS time of the ICI-TKI group was significantly higher than that in the ICI-ICI group (4.1 months and NR, respectively; P=0.0210), and the 50% OS times were 29.8 months and NR (P=0.7343), respectively. In conclusion, according to the analysis of real-world data, good therapeutic efficacy can be achieved with any regimen in patients with recurrence after radical surgery. In addition, improved results could be achieved through treatment with ICI-TKI in patients without upfront CN.

Comparative Efficacy of Combination Therapy of Ipilimumab Plus Nivolumab for Non-clear Cell Renal Cell Carcinoma.

BACKGROUND/AIM: The survival benefit of immune checkpoint inhibitors for non-clear cell renal cell carcinoma (nccRCC) is unclear. Our purpose was to evaluate the real-world survival benefit of ipilimumab plus nivolumab retrospectively. PATIENTS AND METHODS: We retrospectively reviewed medical records of 33 patients with metastatic nccRCC who received combination therapy with ipilimumab plus nivolumab or monotherapy with a molecular targeted agent as initial systemic therapy. Progression-free survival (PFS), overall survival (OS) and objective response rate were compared between the two groups. RESULTS: Median PFS of each therapy was 3.5 and 4.7 months (p=0.61) and median OS was 19.6 and 10.6 months (p=0.23), respectively. Three patients treated with ipilimumab and nivolumab had a complete response, resulting in an objective response rate of 30.0%, while that for molecular targeted therapy was 4.5% (p=0.04). CONCLUSION: Ipilimumab plus nivolumab achieved statistically non-significant, but longer overall survival and significantly higher objective response rate.