Efficacy of Combination Therapy With Radium-223 and Enzalutamide in Castration-resistant Prostate Cancer With Bone Metastases.

BACKGROUND/AIM: Radium-223 therapy has been reported to improve prognosis in patients with castration-resistant prostate cancer (CRPC) and bone metastases. Occasionally, radium-223 and androgen receptor signaling inhibitors (ARSIs) are used in combination for disease control, but the efficacy of this combination is unclear. This study assessed the efficacy of the addition of enzalutamide in patients treated with radium-223. PATIENTS AND METHODS: We included patients with CRPC and bone metastases who were treated with radium-223 at our institution. Patients were assigned to the enzalutamide combination group or non-combination group. We compared progression-free survival (PFS), overall survival (OS), and the completion rate of radium-223 between the two groups. RESULTS: In total, 39 patients with CRPC were included in this retrospective study. The median follow-up duration was 8.8 months. The enzalutamide combination and non-combination groups included 22 (56.4%) and 17 patients (43.6%), respectively. Median PFS was 11.3 months [95% confidence interval (CI)=3.9-19.9] in the combination group, versus 3.0 months (95%CI=1.9-5.5) in the non-combination group (p=0.004). Median OS did not significantly differ between the groups. The radium-223 completion rate was higher in the combination group than in the non-combination group (72.7% vs. 35.3%, p=0.026). CONCLUSION: The combined use of enzalutamide with radium-223 therapy improved PFS and treatment completion rates in patients with CRPC and bone metastases. This combination may be associated with a more favorable prognosis.

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 metastatic 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 regimens was ICI-ICI regimens in 26 cases and ICI-TKI regimens 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 them (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 ICITKI 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.

The harmful effects of overlooking acute bacterial prostatitis.

Prostatitis is a major urological disease affecting 25%-50% of men over their lifetime. However, prostatitis is often overlooked in nonurologic departments due to its sometimes indeterminate symptoms. In this review, we describe how to recognize and treat acute bacterial prostatitis, which manifests as a clinical problem in other departments as well as urology, to help prevent this disease from being overlooked. There are several possible negative effects of not recognizing acute bacterial prostatitis (ABP). First, initial treatment can fail. In the hyperacute phase, common antibiotics are often effective, but in rare cases, such antibiotics may not be effective. In addition, once ABP progresses to form a prostate abscess, potentially avoidable surgical interventions are often needed. A second issue is the transition to chronic prostatitis. If chronic bacterial prostatitis progresses, treatment requires long-term antibiotic administration and the response rate is not high. Some patients may have to deal with urinary tract infections for the rest of their lives. Finally, there is the problem of overlooking the underlying disease. ABP is rare in healthy adult men without underlying disease, including sexually transmitted diseases as well as benign prostatic hyperplasia, urinary stones, and malignant tumors, and may not be obvious. When examining patients with fever of unknown origin, it is necessary to exclude not only infectious diseases but also collagen diseases and malignant tumors. If there are any doubts, we recommend a rectal exam and consultation with a urologist.

Cine magnetic resonance imaging in evaluating retroperitoneal leiomyosarcoma arising from the inferior vena cava.

Introduction: Leiomyosarcoma of the inferior vena cava is associated with poor prognosis. Complete resection is the only curative treatment. We present a patient with this disease in whom cine magnetic resonance imaging was valuable in selecting the surgical strategy and mitigating invasiveness. Case presentation: A 68-year-old woman presented with right-sided abdominal pain. Computed tomography revealed an 86 mm tumor in the right retroperitoneal space that extended into the inferior vena cava and reached superiorly to the right atrium. Percutaneous needle biopsy confirmed leiomyosarcoma. Cine magnetic resonance imaging demonstrated no adhesions between the tumor and the upper segment of inferior vena cava wall, nor with the right atrial wall, indicating resectability. Radical tumor resection was successfully performed without requiring thoracotomy. Conclusion: Cine magnetic resonance imaging appears to be useful in inferior vena cava leiomyosarcoma for evaluating adhesions between the tumor and vessel wall.

Cine magnetic resonance imaging predicts thrombus adhesion in metastatic renal cell carcinoma with an inferior vena cava tumor thrombus: A case of pathological complete response with pembrolizumab plus lenvatinib.

Introduction: Renal cell carcinoma with an inferior vena cava tumor thrombus is a challenging disease that requires a multimodal treatment approach. Pembrolizumab plus lenvatinib has displayed promising efficacy in metastatic renal cell carcinoma. Case presentation: A 61-year-old man was diagnosed with metastatic renal cell carcinoma and a tumor thrombus adhering to the inferior vena cava wall by cine magnetic resonance imaging. After 6 months of pembrolizumab and lenvatinib therapy, tumor shrinkage was detected, excluding the advanced portion of the inferior vena cava thrombus, and nephrectomy and thrombectomy were performed. Adhesion of the tumor thrombus to the inferior vena cava wall was observed during surgery. Resection produced a remarkable pathological complete response with no viable cells in the resected specimens, including the thrombus site. Conclusion: This case highlights the potential of pembrolizumab plus lenvatinib for treating advanced renal cell carcinoma with an inferior vena cava thrombus and the utility of cine magnetic resonance imaging for evaluating thrombus adhesion to the inferior vena cava.

Real-world outcomes of avelumab plus axitinib as first-line therapy in patients with advanced renal cell carcinoma in Japan: A multicenter, retrospective, observational study (J-DART).

OBJECTIVES: In the phase 3 JAVELIN Renal 101 trial in patients with advanced renal cell carcinoma (aRCC), objective response rate (ORR) and progression-free survival (PFS) were significantly improved in patients treated with first-line avelumab plus axitinib vs sunitinib. Here we evaluate real-world outcomes with first-line avelumab plus axitinib in Japanese patients with aRCC. METHODS: In this multicenter, noninterventional, retrospective study, clinical data from patients with aRCC treated with first-line avelumab plus axitinib between December 2019 and December 2020 in Japan were reviewed. Endpoints included ORR and PFS per investigator assessment, and time to treatment discontinuation (TTD). RESULTS: Data from 48 patients (median age, 69 years) from 12 sites were analyzed. Median follow-up was 10.4 months (range, 2.6-16.5), and median duration of treatment was 7.4 months (range, 0.5-16.5). International Metastatic RCC Database Consortium risk category was favorable, intermediate, or poor in 16.7%, 54.2%, and 29.2% of patients, respectively. The ORR was 48.8% (95% CI, 33.3%-64.5%), including complete response in 3/43 patients (7.0%). Thirteen patients (27.1%) had disease progression or died, and median PFS was 15.3 months (95% CI, 9.7 months - not estimable). At data cutoff, 24 patients (50.0%) were still receiving avelumab plus axitinib, and median TTD was 15.2 months (95% CI, 7.4 months - not estimable). Three patients (6.3%) received high-dose corticosteroid treatment for immune-related adverse events, and 8 (16.7%) received treatment for infusion-related reactions. CONCLUSIONS: We report the first real-world evidence of the effectiveness and tolerability of first-line avelumab plus axitinib in Japanese patients with aRCC. Results were comparable with the JAVELIN Renal 101 trial.

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.

Renal cell carcinoma in the contralateral kidney with TFE3 gene translocation following chemotherapy for childhood nephroblastoma: A case report and literature review.

Key Clinical Message: Renal cell carcinoma as a secondary malignant neoplasm is relatively rare; however, the possibility of secondary renal cell carcinoma following chemoradiotherapy for childhood nephroblastoma should be considered. Abstract: The occurrence of secondary renal cell carcinoma (RCC) following chemoradiotherapy for nephroblastoma is relatively rare, especially in microphthalmia transcription factor family translocation renal cell carcinoma. A 13-year-old Japanese male was referred to our department for treatment of a right kidney mass. The patient had undergone open left nephrectomy and adjuvant chemotherapy for nephroblastoma, 12 years before. Diagnostic imaging revealed a tumor in the right kidney and a lesion suspected to be metastasis in the left eighth rib. Chromophobe RCC or translocation RCC was suspected from the imaging pattern. TNM classification was cT1aN0M1, and the clinical stage was IV. Partial nephrectomy by robot-assisted surgery for the right renal tumor and resection of the left eighth rib were performed. Pathologically, the renal tumor was diagnosed as translocation RCC, and the rib lesion demonstrated no evidence of malignancy. We are currently undergoing imaging follow-up and the patient has been recurrence-free for 15 months. In this study, we present a rare case of secondary translocation RCC after successful treatment of nephroblastoma.

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.

Urinary tract infections after retrograde pyelography and prophylactic antibiotics.

INTRODUCTION: Retrograde pyelography (RP) is performed for examination of upper urinary tract cancers and hydronephrosis. Although urinary tract infections (UTI) are known to be complicated by the examination, there are few reports on the frequency of occurrence and prophylactic antibiotics. METHODS: The incidence of UTI and febrile UTI (f-UTI) and patient background information were compared in 388 patients who underwent RP at our hospital from January 2018 to December 2022. We also examined the administration of pre-RP antibiotics. RESULTS: Of the 388 patients who underwent RP, 27 (6.9%) had UTI and 17 (4.4%) had f-UTI. Of the 27 UTI cases, 25 (92.6%) were pyelonephritis; 20 (74.0%) were hospitalized and 2 (7.4%) presented with septic shock and were managed in the intensive care unit. When comparing the background of patients with UTI, no significant differences were found in the present study, but when limited to the 17 cases of f-UTI, the presence of hydronephrosis before RP and not prescribing antibiotics before RP were associated with significantly higher incidence of f-UTI (p = 0.019, p = 0.036, respectively). Especially for patients without pyuria and bacteriuria before RP, prescribing antibiotics before RP resulted in 0 cases of f-UTI (p = 0.020). CONCLUSION: This retrospective study showed that the presence of hydronephrosis before RP and not prescribing prophylactic antibiotics before RP are risk factors for f-UTI.

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.

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.

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.

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.

Proapoptotic effect of nonthermal pulsed ultrasound on prostate cancer cells in a nude mouse model.

BACKGROUND: Ultrasound (US) can induce cell injury, and we have previously reported that adjusting the pulse repetition frequency (PRF) of ultrasound output can induce prostate cancer cell destruction without causing a rise in the temperature of the irradiated area. In this study, we examined the mechanism of nonthermal ultrasound cell destruction, which was not fully clarified in our previous reports. METHODS: In vitro, we evaluated postirradiation cells immediately after treatment and examined membrane disruption by proliferation assay, LDH assay, and apoptosis assay. In vivo, we injected mice with human LNCaP and PC-3 prostate cancer cells and evaluated the therapeutic effects of US irradiation by H-E staining and immunostaining. RESULTS: Proliferation assays showed inhibition at 3 h postirradiation independently of PRF and cell line (p < 0.05). Quantitative assessment of apoptosis/necrosis by flow cytometry showed widely varying results depending on cell type. LNCaP showed an increase in late apoptosis at 0 h independent of PRF (p < 0.05), while PC-3 showed no significant difference at 0 h. The LDH assay showed an increase in LDH independent of PRF in LNCaP (p < 0.05 respectively), but no significant difference in PC-3. In vivo, tumor volume was compared and a significant reduction was observed at 10 Hz for LNCaP (p < 0.05) and 100 Hz for PC-3 (p < 0.001) at 3 weeks after the start of irradiation. The excised tumors were evaluated with Ki-67, Caspase-3, and CD-31 and showed a significant treatment effect independent of cell type and PRF (p < 0.001 respectively). CONCLUSION: Examining the mechanism behind the therapeutic effect of US irradiation revealed that the main effect was achieved by apoptosis induction rather than necrosis.

Efficacy and safety of apalutamide in patients with metastatic castration-resistant prostate cancer (GENESIS): protocol for a multicentre, open-label, single-arm clinical trial.

INTRODUCTION: This is a multicentre, open-label, single-arm clinical trial to evaluate the efficacy and safety of apalutamide in patients with metastatic castration-resistant prostate cancer. METHODS AND ANALYSIS: The trial will be performed at 4 university hospitals and 14 city hospitals in Japan. The target number of patients will be 110. The patients will be orally administered 240 mg apalutamide once daily during the treatment period. The primary outcome is the prostate-specific antigen (PSA) response rate. PSA response is defined as ≥50% decline from baseline at 12 weeks. Secondary outcomes are time to PSA progression, progression-free survival, overall survival, progression-free survival during second therapy, ≥50% decline in PSA from baseline at 24 and 48 weeks, ≥90% decline in PSA from baseline or lower PSA detection sensitivity after the initial dose at 12, 24 and 48 weeks, PSA maximal changes, accumulated PSA response from screening to 24 and 48 weeks, and grade 3 or 4 adverse events according to the Common Terminology Criteria for Adverse Events version 4.0. ETHICS AND DISSEMINATION: This study has been approved by the Certified Research Review Board of Kobe University (No. CRB5180009). All participants will be required to provide written informed consent. Findings will be disseminated through scientific and professional conferences and peer-reviewed journal publications. The datasets generated during the study will be available from the corresponding author on reasonable request. TRIAL REGISTRATION NUMBER: jRCTs051220077.

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.

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.

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.