Utility of a 3 mm Bipolar Instrument in Laparoscopic Renal Surgery Using the Senhance Robotic System.

We report our initial experience and the utility of 3 mm bipolar forceps in laparoscopic renal surgery using the Senhance robotic system. We performed laparoscopic nephroureterectomy for upper tract urothelial carcinoma in two patients: an 80-year-old female with a left renal pelvic tumor and an 80-year-old male with a right ureteral tumor. Both surgeries were successfully completed without conversion to conventional laparoscopic surgery or laparotomy. The console times for the procedures were 101 and 108 minutes, with estimated blood losses of 5 and 50 milliliters, respectively. The postoperative courses were uncomplicated, with histopathological examinations confirming high-grade urothelial carcinoma with negative surgical margins in both patients. The 3 mm Maryland bipolar instrument was able to grasp membranes with sufficient gentleness and precision. The relatively narrow diameter of the shaft posed a challenge in terms of shaft strength; however, it did not deflect even when it was used to lift the kidney, indicating sufficient robustness. When utilized in the cutting mode, the incision capacity of the 3 mm Maryland bipolar instrument was higher than that of the 5 mm instrument, which allowed for expedient and precise incision. Since only the tissue held by the forceps was incised, it was possible to perform a safe incision even in areas near blood vessels and other organs. Although the tip of the 3 mm Maryland instrument is more sharply pointed than that of the 5 mm instrument, no tissue damage was observed even when the 3 mm instrument was used for blunt dissection. Our initial results suggest that the 3 mm Maryland bipolar instrument is efficacious for performing laparoscopic renal surgery. The instrument may be suitable for a range of surgical procedures in laparoscopic renal surgery using the Senhance system. Further studies are necessary to establish the role and effectiveness of this instrument in broader clinical applications.

Prognostic significance of inflammatory markers in patients with advanced renal cell carcinoma receiving nivolumab plus ipilimumab.

BACKGROUND: A useful biomarker for the efficacy of immune checkpoint inhibitors (ICIs) in advanced renal cell carcinoma (RCC) has not yet been established. This study aims to investigate whether inflammatory markers are associated with the efficacy of nivolumab plus ipilimumab therapy before and during treatment. METHODS: Data from patients with advanced clear cell RCC who received a combination treatment of nivolumab plus ipilimumab were retrospectively analyzed. The neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and C-reactive protein (CRP) levels were assessed at baseline and 3, 6, and 9 weeks after treatment initiation. The correlation between these inflammatory markers and the patient's prognosis was investigated. RESULTS: Eighty-four patients were identified. The multivariate analysis identified NLR at week 3, CRP at week 6, and NLR and CRP at week 9 as the consistent predictor associated with poor overall survival (OS) at each time point. The survival analysis and receiver operating characteristic (ROC) curve analysis revealed that an NLR of ≥ 2.4 at week 3, CRP of ≥ 1.4 mg/dL at week 6, and NLR of ≥ 4.8 and CRP of ≥ 1.0 mg/dL at week 9 were associated with worse OS (hazard ratios (HR) = 5.70, P = 0.008, HR = 3.23, P = 0.004, HR = 7.38, P < 0.001 and HR = 3.55, P = 0.002). CONCLUSIONS: Both NLR and CRP were considered useful biomarkers for understanding the prognosis during nivolumab plus ipilimumab therapy. Furthermore, an NLR of ≥ 4.8 and CRP of ≥ 1.0 mg/dL at week 9 are helpful in reconsidering treatment continuation.

Aggressive variant prostate cancer with multiple subcutaneous metastases: a case report.

A 71-year-old man with bone metastasis of hormone-sensitive prostate cancer was treated with androgen deprivation therapy and apalutamide. Radium-223 and radiation therapy were administered after it become castration resistant. Although prostate-specific antigen levels remained low, multiple subcutaneous metastases of neuroendocrine prostate cancer were observed. A review of the pre-treatment prostate needle biopsy revealed a small component with features suggestive of neuroendocrine differentiation. Phosphatase and tensine homolog loss and tumor protein p53 overexpression were observed, confirming the diagnosis of aggressive variant prostate cancer. Platinum-based chemotherapy was administered; however, the patient died 28 months after diagnosis. In this case, if the diagnosis of aggressive variant prostate cancer had been made at an earlier time by biopsy specimens, there might have been a possibility to improve the prognosis by the earlier introduction of the platinum-based regimen. Supplementary Information: The online version contains supplementary material available at 10.1007/s13691-024-00673-7.

Robot-Assisted Partial Cystectomy Using the "Double Bipolar Method".

The "double bipolar method" (DBM) in robotic surgery has been widely used in Japanese general surgery and gynecology; however, it is not commonly used in the field of urology. A 55-year-old female was diagnosed with stage IA endometrial cancer. A 2-cm cystic lesion was incidentally observed at the dome of the bladder on magnetic resonance imaging. A simultaneous robot-assisted total hysterectomy and partial cystectomy using the da Vinci Xi system was planned. The gynecological procedure was first performed with the DBM, and the DBM was also used in the partial cystectomy without additional instruments to reduce surgical costs. Maryland bipolar forceps was used to excise the peritoneum, fat, and bladder wall without bleeding, enabling delicate and precise resection using the forceps' tips. Robot-assisted partial cystectomy using the DBM was feasible. When performing combined surgeries with other departments, if the DBM is already being utilized, it is worthwhile to attempt to decrease surgical cost.

Association between response to enfortumab vedotin and peripheral neuropathy in urothelial carcinoma patients: a multicenter retrospective study.

BACKGROUND: Enfortumab vedotin (EV) was approved for patients with metastatic urothelial carcinoma (mUC) who progressed after anticancer therapy on September 2021 in Japan. The association between the occurrence of EV-related side effects and clinical outcome remains to be elucidated. METHODS: We identified 97 mUC patients treated with EV therapy at our five institutions from the date of approval to March 2023. The median follow-up period was 7.0 months. We retrospectively analyzed the efficacy and safety of EV. RESULTS: The median age of the patients was 71 years old, 39% had PS of 1 or more, and 56.7% had primary tumor in upper urinary tract. Overall response rate (ORR) to EV therapy, median progression-free survival (PFS), and overall survival (OS) were 43.3%, 7.52 months, and 12.78 months, respectively. Any grade of treatment-related skin disorder, dysgeusia, peripheral neuropathy, gastrointestinal disorder, and hyperglycemia occurred in 61 (62.9%), 36 (37.1%), 34 (35.1%), 29 (29.9%), and 18 (18.6%) patients, respectively. The patients with EV-associated peripheral neuropathy had significantly higher ORR (58.8% vs. 34.9%, P = .032) and longer median PFS (8.05 vs. 6.31 months, P = .017) and OS (not reached vs. 11.57 months, P = .008, respectively) than those without. The occurrence of peripheral neuropathy after EV treatment and the presence of peritoneal dissemination were factors independently associated with PFS (hazard ratio = 0.46, P = .008 and hazard raito = 3.83, P = .004, respectively) and OS (hazard ratio = 0.30, P = .005 and hazard raito = 4.53, P = .002, respectively). CONCLUSIONS: The occurrence of EV-related peripheral neuropathy might be associated with the efficacy of EV therapy in mUC patients.

Choroidal Metastasis From Papillary Renal Cell Carcinomas: A Case Report and a Review of the Literature.

Choroidal metastasis originating from renal cell carcinomas (RCCs) is rare. To the best of our knowledge, 31 cases of choroidal metastasis from RCC have been reported in the English literature as of January 31, 2024. Nevertheless, physicians need to be vigilant in recognizing this condition, as its progression impacts the quality of life (QOL) of affected patients. In Case 1, a 60-year-old male with a medical history of papillary RCC experienced a deterioration in visual acuity (VA) and was diagnosed with solitary choroidal metastasis. Subsequently, multiple metastases were identified, prompting the initiation of a combination therapy regimen consisting of pembrolizumab plus axitinib. Despite treatment, progression of choroidal metastasis and a further decline in VA were observed. The patient underwent stereotactic radiotherapy and experienced complete resolution of the choroidal metastasis, accompanied by a slight improvement in VA. In Case 2, a 76-year-old man presented with a renal tumor accompanied by lung metastases. He underwent nephrectomy, and the histological diagnosis was papillary RCC. We initiated combination therapy consisting of nivolumab plus cabozantinib. The patient experienced a decrease in VA during treatment. We identified extensive fine metastases scattered throughout the bilateral choroid. We administered axitinib, but the patient experienced bilateral blindness. Given the absence of established therapy for choroidal metastasis, it is crucial to maintain flexibility in treatment selection. Local or systemic approaches should be used as deemed appropriate for each individual case.

Photodynamic diagnosis-assisted transurethral resection of bladder tumor for high-risk non-muscle invasive bladder cancer improves intravesical recurrence-free survival (BRIGHT study).

OBJECTIVES: In a primary analysis of data from the BRIGHT study (UMIN000035712), photodynamic diagnosis-assisted transurethral resection of bladder tumor (PDD-TURBT) using oral 5-aminolevulinic acid hydrochloride reduced residual tumors in high-risk non-muscle invasive bladder cancer (NMIBC). We aimed to evaluate the effectiveness of PDD-TURBT for intravesical recurrence after a second transurethral resection for high-risk NMIBC. METHODS: High-risk NMIBC patients initially treated with PDD-TURBT (PDD group) were prospectively registered between 2018 and 2020. High-risk patients with NMIBC who were initially treated with white-light TURBT (WL group) were retrospectively registered. Intravesical recurrence-free survival after the second transurethral resection was compared between the PDD and WL groups using propensity score matching analysis. RESULTS: In total, 177 patients were enrolled in the PDD group, and 306 patients were registered in the WL group. After propensity score matching (146 cases in each group), intravesical recurrence within 1 year was significantly less frequent in the PDD group than in the WL group (p = 0.004; hazard ratio [HR] 0.44, 95% confidence interval [CI]: 0.25-0.77). In subgroup analysis, PDD-TURBT showed a particularly high efficacy in reducing intravesical recurrence within 1 year, especially in cases of tumors measuring less than 3 cm (p = 0.003; HR 0.31, 95% CI: 0.14-0.67), absence of residual tumor at second transurethral resection (p = 0.020; HR 0.37, 95% CI: 0.16-0.86), and no postoperative intravesical Bacillus Calmette-Guérin therapy (p < 0.001; HR 0.27, 95% CI: 0.13-0.58). CONCLUSIONS: PDD-TURBT may reduce short-term intravesical recurrence in patients with high-risk NMIBC.

Differences in oncological benefits from second transurethral resection between white-light initial surgery and photodynamic diagnosis-guided initial surgery for primary high-risk non-muscle invasive bladder cancer.

OBJECTIVES: The aim of this study was to compare clinical outcomes between patients receiving second TUR after initial white-light transurethral resection of bladder tumor (WL-TURBT) and initial photodynamic diagnosis (PDD)-assisted TURBT. METHODS: A total of 1007 patients were divided into four groups based on the treatment pattern: WL-TURBT with second TUR (161 patients, WL-second group) or without second TUR (540 patients, WL-alone group) and PDD-TURBT with second TUR (112 patients, PDD-second group) or without second TUR (194 patients, PDD-alone group). Oncologic outcomes (bladder cancer recurrence, progression, urothelial cancer-specific mortality) and rates of residual tumor and risk stratification of non-muscle-invasive bladder cancer (NMIBC) after second TUR were evaluated. RESULTS: After propensity score-matching 121 patients were included each in the WL-alone and WL-second groups, and 63 patients each in the PDD-alone and PDD-second groups. In the WL group, the second TUR was significantly associated with improved progression-free (p = 0.012) and urothelial cancer-specific free survival (p = 0.011), but not with recurrence-free survival (p = 0.93). Patients initially treated with PDD-TURBT, and with a tumor diameter <30 mm and multifocality had a relatively high benefit from second TUR. The rates of residual tumor and risk stratification of NMIBC did not significantly differ between WL-TURBT and PDD-TURBT groups. CONCLUSIONS: Our findings suggested that a second TUR could be omitted after an initial PDD-TURBT in selected patients with high-risk NMIBC.

Methotrexate-associated lymphoproliferative disorder: A rare pancreatic tumor diagnosed via endoscopic ultrasound-guided fine-needle biopsy.

A 73-year-old woman with a history of rheumatoid arthritis treated with methotrexate (MTX) for the last 10 years was referred to our hospital for a pancreatic tumor examination. Contrast-enhanced abdominal computed tomography revealed a 20-mm-diameter hypovascular tumor in the pancreatic tail. A hypoechoic mass with heterogeneous internal echo was found on an endoscopic ultrasound (EUS). An EUS-guided fine-needle biopsy (EUS-FNB) was performed with a 22-gauge Franseen-tip needle. Histologic examination of EUS-FNB specimens from the pancreatic tumor revealed the proliferation of atypical spindle cells. Immunohistochemical staining for CD20 and Ki-67 was positive in the atypical cells. Immunohistochemical staining for CD3 was partially positive in the atypical cells. Epstein-Barr virus-encoded RNA in situ hybridization showed positive staining. MTX-related lymphoproliferative disorder (MTX-LPD) with Epstein-Barr virus infection was diagnosed. MTX treatment was immediately discontinued, and treatment was initiated by a hematologist. However, her condition rapidly deteriorated, and she died of multiple organ failure 4 weeks after diagnosis. MTX-LPD can complicate gastrointestinal lesions. However, most lesions are localized in the stomach and rarely complicate pancreatic lesions. MTX-LPD is classified as an "iatrogenic" LPD. Therefore, immediate action, such as MTX discontinuation, is necessary. In conclusion, endoscopists should be aware that MTX-LPD lesions can occur in the pancreas and gastrointestinal tract. Moreover, EUS-FNB can be useful in the diagnosis of this rare pancreatic tumor.

New risk stratification for adjuvant nivolumab for high-risk muscle-invasive urothelial carcinoma.

Objectives: We aim to evaluate the risk of recurrence after neoadjuvant chemotherapy followed by radical cystectomy, particularly in ypT2 disease in patients with urothelial carcinoma, because it is not clear if all eligible patients with high-risk muscle-invasive urothelial carcinoma should be treated with adjuvant nivolumab. Materials and Methods: We analysed the radiological and clinicopathological features, including cT and ypT stages, of 197 patients who had undergone two to four cycles of cisplatin-based neoadjuvant chemotherapy and radical cystectomy without adjuvant chemotherapy. We stratified the risk of postoperative recurrence by these factors. Results: The median observation period was 29.6 (interquartile range, 11.4-71.7) months, and disease recurrence was observed in 58 patients. Multivariate analysis revealed that ypT stage (P = 0.019) and lymphovascular invasion (P = 0.015) were independent risk factors for postoperative recurrence. The ypT2 group (n = 38) had significantly better recurrence-free survival than the ypT3 group (n = 41) (median recurrence-free survival: not reached vs. 13.4 months, respectively, P = 0.005). In ypT2 disease, the cT2 and ypT2 group (n = 15), which was diagnosed as cT2 preoperatively and then diagnosed as ypT2 postoperatively, had significantly better recurrence-free survival than the cT3/4 and ypT2 group (n = 23) (median recurrence-free survival: not reached vs. 63.1 months, respectively, P = 0.034). There was no significant difference in recurrence-free survival between the ypT ≤ 1 (n = 106) and the cT2 and ypT2 groups (median recurrence-free survival: not reached in both, P = 0.962). Conclusion: Patients with cT2 and ypT2 stage have a relatively low risk of recurrence and thus have a lower need for adjuvant nivolumab, particularly those with ypT2.

Improvement of liver histology in hepatic sarcoidosis due to treatment with corticosteroids and ursodeoxycholic acid: a case report.

We report the case of a 48-year-old male with a history of pulmonary and ocular sarcoidosis. Non-caseating granulomas, identified histologically, are the most characteristic manifestation of sarcoidosis. Hepatic sarcoidosis is difficult to diagnose using radiological imaging. In the patient reported in this study, ultrasound and contrast-enhanced computed tomography scans identified multiple intra-abdominal lymphadenopathies, with evidence of liver and splenic infiltrations. The first liver biopsy revealed non-caseating granulomatous hepatitis consistent with hepatic sarcoidosis. The patient was treated with ursodeoxycholic acid (UDCA), but his laboratory parameters did not improve. Prednisone was initiated at a dose of 30 mg daily and slowly tapered. At a dose of 12.5 mg daily, marked improvements in the fibrotic and sarcoid-like lesions were noted at the second biopsy. A third biopsy was performed, with the patient on a prednisone taper of 5 mg/day showed mild fibrous expansion in the portal tracts and mild parenchymal necro-inflammatory lesions. However, overall, fibrosis marker levels remained stable over the course of treatment. A fourth biopsy was performed after a 5-year course of 5 mg/day prednisone. This revealed minimal lobular inflammation without fibrosis. Thus, treatment of this patient with corticosteroids and UDCA resulted in marked improvements in his biochemical and histological parameters.

Comparative assessment of disease recurrence after transurethral resection of non-muscle-invasive bladder cancer with and without a photodynamic diagnosis using 5-aminolevulinic acid: a propensity score-matching analysis.

BACKGROUND: Among patients with non-muscle-invasive bladder cancer (NMIBC), systematic reviews showed lower recurrence rate in patients treated with photodynamic diagnosis (PDD)-assisted transurethral resection of bladder tumor (TURBT) than with white-light (WL) TURBT. However, the result is not consistent between clinical trials and the significance of preoperatively available factors in disease recurrence after PDD-TURBT remains unclear. METHODS: The present study retrospectively analyzed 1174 NMIBC patients who underwent TURBT and were followed up for ≥ 6 months. Among 1174 patients, 385 and 789 underwent PDD-TURBT with oral 5-aminolevulinic acid (the PDD group) and WL-TURBT (the WL group), respectively. Recurrence-free survival (RFS) was compared between the PDD and WL groups before and after propensity score matching, and the impact of several baseline parameters on RFS between the 2 groups was investigated after matching. RESULTS: Before propensity score matching, RFS was significantly longer in the PDD group than in the WL group (P = 0.006). After matching, 383 patients were included in both groups, and RFS was significantly longer in the PDD group than in the WL group (P < 0.001). In the cohort after matching, RFS between the two groups was compared in each subgroup classified according to baseline parameters, including age, sex, history of previous or concomitant upper urinary tract urothelial carcinoma, preoperative urinary cytology, tumor multiplicity, and tumor size, and significantly longer RFS was observed in the PDD group in all subgroups, except for the patients with tumors ≥ 30 mm (P = 0.21). CONCLUSION: These results suggest that PDD-TURBT prolongs RFS in NMIBC patients, except for those with tumors ≥ 30 mm.

Association between immune-related adverse events and survival in patients with renal cell carcinoma treated with nivolumab plus ipilimumab: immortal time bias-corrected analysis.

BACKGROUND: Immune-related adverse events (irAEs) in patients treated with immune check inhibitors are associated with favourable response rate and survivals in multiple cancers, including renal cell carcinoma (RCC). The aim of this study was to investigate how irAEs were associated with improved survivals in advanced RCC patients treated with nivolumab plus ipilimumab. MATERIALS AND METHODS: This retrospective study included patients who received nivolumab plus ipilimumab at six centres, institutions, or hospitals between September 2018 and February 2022. We assessed associations of the development and the number of irAEs with overall survival (OS) and progression-free survival (PFS). To eliminate immortal time bias, landmark analysis and a Cox model with time-dependent variables were used. RESULTS: This study included 129 patients with a median follow-up of 12.3 months. The 2-year OS and PFS rates were 55% and 42%, respectively. Ninety six patients experienced irAEs. The development of irAEs was positively associated with OS and PFS rates (hazard ratio [HR] 0.328, 95% confidence interval [CI] 0.165-0.648, p = 0.001; HR 0.334, 95% CI 0.151-0.737, p = 0.007). Patients who experienced multiple irAEs had longer OS (HR 0.507, 95% CI 0.235-1.097, p = 0.085 or HR 0.245, 95% CI 0.110-0.544, p < 0.001) and PFS (HR 0.572, 95% CI 0.316-1.036, p = 0.085 or HR 0.267, 95% CI 0.113-0.628, p = 0.002) compared with those who experienced single or zero irAE. CONCLUSIONS: Developing irAEs, particularly multiple irAEs, is associated with favourable survivals in advanced RCC patients treated with nivolumab plus ipilimumab.

Impact on Japanese healthcare economics of photodynamic diagnosis-assisted transurethral resection of bladder tumor for non-muscle invasive bladder cancer: A multicenter retrospective cohort study.

OBJECTIVES: Bladder cancer, especially non-muscle invasive bladder cancer (NMIBC), is one of the most costly cancers owing to its long-term management. Photodynamic diagnosis-assisted transurethral resection of bladder tumor (PDD-TURBT) reduces the risk of intravesical recurrence. However, its impact on healthcare economics in Japan remains unclear. We evaluated the comprehensive medical costs of Japanese healthcare economics regarding PDD-TURBT. METHODS: This large-scale, multicenter, retrospective study included a dataset of 1531 patients who were diagnosed with primary NMIBC who underwent initial TURBT between April 2006 and June 2021. A one-to-one propensity-score matching analysis was used for an unbiased comparison based on postTURBT follow-up periods. The total medical costs, including hospitalization, surgical procedures for TURBT and salvage radical cystectomy, adjuvant intravesical therapies, and follow-up examinations, were compared between white light (WL)-TURBT and PDD-TURBT groups. RESULTS: After propensity-score matching, 468 patients each of WL- and PDD-TURBT groups were matched. Total costs were 510 337 128 and 514 659 328 ¥ in WL- and PDD-TURBT groups, respectively. The costs of adjuvant intravesical therapies, follow-up examinations, and salvage radical cystectomy in PDD-TURBT group were equivalent to or lower than those in WL-TURBT group. Furthermore, total costs of high- and highest-risk NMIBC in PDD-TURBT group were either equivalent or lower compared to those in WL-TURBT group. CONCLUSIONS: The total costs associated with PDD-TURBT were higher compared to WL-TURBT, while there is the potential of PDD-TURBT to reduce the burden on healthcare economics in limited cases.

Additional oncological benefit of photodynamic diagnosis with blue light cystoscopy in transurethral resection for primary non-muscle-invasive bladder cancer: A comparative study from experienced institutes.

Objectives: The objective of this work is to evaluate the additional oncological benefit of photodynamic diagnosis (PDD) using blue-light cystoscopy in transurethral resection (TURBT) for primary non-muscle-invasive bladder cancer (NMIBC) based on the International Bladder Cancer Group (IBCG)-defined progression and the subsequent pathological pathways. Patients and Methods: We reviewed 1578 consecutive primary NMIBC patients undergoing white-light TURBT (WL-TURBT) or PDD-TURBT during 2006-2020. One-to-one propensity score-matching was performed using multivariable logistic regression to obtain balanced groups. IBCG-defined progression of NMIBC included stage-up and grade-up as well as conventional definitions such as the development of muscle-invasive BC or metastatic disease. Nine oncological endpoints were evaluated. Sankey diagrams were generated to visualize follow-up pathological pathways after the initial TURBT. Results: Comparison of event-free survival between the matched groups revealed that PDD use decreased the bladder cancer recurrence risk and IBCG-defined progression risk, whereas no significant difference was noted in conventionally defined progression. This was attributable to a reduced risk of stage-up, from Ta to T1, and grade-up. Sankey diagrams of the matched groups showed that patients with primary Ta low-grade tumour and first-recurrence Ta low-grade tumour did not have bladder recurrence or progression, while some of those in the WL-TURBT group developed recurrence after treatment. Conclusions: The multiple survival analysis demonstrated that the risk of IBCG-defined progression was significantly decreased by PDD use in NMIBC patients. Sankey diagrams revealed possible differences in pathological pathways after the initial TURBT between the two groups, demonstrating that repeated recurrence could be prevented by PDD use.

Clinical outcomes of nivolumab plus ipilimumab in patients with metastatic non-clear cell renal cell carcinoma: Real-world data from a Japanese multicenter retrospective study.

OBJECTIVES: Although nivolumab plus ipilimumab has become a standard treatment regimen for metastatic clear cell renal cell carcinoma (ccRCC), its efficacy in non-clear cell carcinoma (nccRCC) has not been fully examined. In the current study, we evaluated the clinical outcomes of nivolumab plus ipilimumab in nccRCC compared with ccRCC. METHODS: We retrospectively analyzed 22 patients with metastatic and/or locally advanced unresectable nccRCC who received nivolumab plus ipilimumab as a first-line therapy and compared them with 107 patients with ccRCC. Objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and toxicity were compared between the nccRCC and ccRCC groups. RESULTS: The histology of nccRCC included eight papillary, six unclassified, three chromophobe, two collecting duct carcinoma, and three other subtypes. Best objective response in nccRCC patients included three complete responses and five partial responses, resulting in an ORR of 36%, while that in ccRCC patients was 50% (p = 0.22). With a median follow-up of 11.9 months, OS was significantly shorter in patients with nccRCC than in those with ccRCC (median 20.8 months vs. not reached, p = 0.04), while there was no significant difference in PFS (median 6.3 vs. 10.8 months, p = 0.21). Treatment-related adverse events occurred in 14 (64%) nccRCC patients and 81 (76%) ccRCC patients. CONCLUSIONS: Combination treatment with nivolumab and ipilimumab demonstrated modest clinical efficacy in patients with nccRCC compared with patients with ccRCC, suggesting it could be a therapeutic option for metastatic nccRCC patients.

Progressive metastatic pheochromocytoma induced by multiple endocrine neoplasia type 2A with a lethal outcome.

Introduction: Patients with multiple endocrine neoplasia type 2A (MEN2A) harboring a pathological variant in the RET gene are characterized by medullary thyroid carcinoma (MTC), pheochromocytoma, and hyperparathyroidism. Although pheochromocytoma is currently defined as a malignant tumor, MEN2A-associated pheochromocytoma is known to have a small risk of metastasis. Case presentation: The case was a 62-year-old Japanese male with bilateral pheochromocytoma, multiple metastases in the liver and bones, and a cardiac thrombus. Genetic testing revealed a pathological variant at codon 634 of the RET gene, thereby leading a diagnosis of MTC. We considered that the multiple metastases were due to MTC; however, a liver biopsy revealed metastasis of pheochromocytoma. Conclusion: When pheochromocytoma precedes MTC, the diagnosis of MEN2A may be difficult.

Efficacy of abiraterone acetate for high-risk hormone-naïve metastatic prostate cancer: A comparison with combined androgen blockade therapy with bicalutamide and androgen deprivation therapy alone.

BACKGROUND: The treatment landscape for men with metastatic hormone-naïve prostate cancer (mHNPC) has dramatically changed with the approval of next-generation anti-androgen drugs. We compared the treatment efficacy of abiraterone with that of combined androgen blockade (CAB) therapy and androgen deprivation therapy (ADT) alone in men with high-risk mHNPC. METHODS: In total, 146 Japanese men with high-risk mHNPC were retrospectively analyzed. As initial hormonal therapy, 30, 83, and 33 men were treated with ADT plus abiraterone (ABI group), ADT plus bicalutamide (CAB group), and ADT alone (ADT group), respectively. Treatment efficacy was compared using time to castration resistance (TTCR) and prostate-specific antigen (PSA) response among the groups. Propensity score matching analysis was also performed to adjust for baseline differences. RESULTS: The median (95% confidence interval [CI]) TTCR in the ABI, CAB, and ADT groups were not reached, 10.7 (7.6-13.8) months and 11.0 (7.9-12.4) months, respectively, and it was significantly longer in the ABI group than in the other groups (p = 0.0012, p = 0.0008). In propensity score matching analysis, the median TTCR was also significantly longer in the ABI group than in the other groups (hazard ratio [HR], 0.47; 95% CI, 0.22-0.98; p = 0.010; HR, 0.32; 95% CI, 0.12-0.85; p = 0.004). The number of men who achieved PSA levels ≤0.2 ng/mL after propensity score matching were significantly higher in the ABI group than in the other groups. CONCLUSIONS: Our results provide important evidence regarding the superiority of abiraterone over CAB therapy and ADT alone for initial treatment for men with newly diagnosed mHNPC.

Predictive factors for the effectiveness of novel androgen receptor axis-targeted agents in patients with metastatic prostate cancer.

OBJECTIVE: Novel androgen receptor axis-targeted agents (ARATAs) have been developed for mCRPC and improved overall survival (OS). Here, we aimed to find predictors who will receive the greatest benefits from ARATAs. METHODS: We previously performed a multicenter study to identify prognostic factors for metastatic hormone-sensitive prostate cancer (mHSPC, n = 148) and mCRPC (n = 99), and showed that the bone scan index (BSI) was one of the significant prognostic factors for 3-year OS (PROSTAT-BSI study). mHSPC progressed to mCRPC (n = 101), for which 69 patients were treated with (n = 39) or without ARATAs (n = 30, prior to the approval of ARATAs). The 69 patients were divided into two groups according to patient factors, and these cohorts were further divided into two subgroups by usage of ARATAs. OS was compared between subgroups in each group. RESULTS: The predictors were age (<71.4 years), serum levels of C-reactive protein (≥0.16 ng/ml) and alkaline phosphatase (≥548 U/L), time to PSA progression after ADT (<8.9 months), the lowest PSA level (≥1 ng/ml) after ADT, and the rate of PSA decline 3 months after ADT (<0.987), whereas hemoglobin levels, PSA before ADT, Gleason scores, existence of visceral metastases, and BSI were not. CONCLUSIONS: The present study identified predictors for the effectiveness of ARATAs. The number of bone metastases (≒BSI), existence of visceral metastases, and Gleason scores, which were identified as high-risk factors in the LATITUDE study and disease volume in CHAARTED criteria, did not appear to be useful for predicting effectiveness from ARATAs.

Case Study: A Japanese patient with metastatic renal cell carcinoma who achieved long-term treatment-free survival with pembrolizumab and axitinib in the KEYNOTE-426 phase III trial of pembrolizumab and axitinib versus sunitinib.

Introduction: Our patient treated with pembrolizumab and axitinib is one of the longest survivors in Japan on KEYNOTE 426, despite adverse events, including delayed-onset hepatitis. We herein present a detailed clinical course and short discussion on the case. Case presentation: This was a 49-year-old male with clear cell renal cell carcinoma and lung metastases. After cytoreductive nephrectomy, treatment with pembrolizumab plus axitinib was initiated and the patient demonstrated a radiographic partial response as best response. The main adverse event was pembrolizumab-induced delayed-onset hepatitis, which was successfully treated with prednisolone. Pembrolizumab was re-initiated and completed. Conclusion: The survival benefit in the present case may be due to the initial potent anti-cancer effects of axitinib and durable immune effects of pembrolizumab, leading to long-term treatment-free survival.