Nobuo Shinohara

Objective: To clarify stage‐ and age‐specific overall survival (OS) according to histological subtype among surgically treated patients with RCC in Japan, we analyzed a nationwide hospital‐based cancer registry. Methods: We analyzed data from the Japanese nationwide hospital‐based cancer registry and identified patients newly diagnosed with RCC between 2012 and 2014. Eligible patients underwent surgical treatment and had histologically confirmed clear cell, papillary, or chromophobe RCC with pathological stage (pStage) I–IV according to the UICC TNM classification, 7th edition. Patients treated with radiotherapy or local ablative therapies were excluded. OS was estimated using the Kaplan–Meier method and compared using the log‐rank test. Results: A total of 17 935 patients met the inclusion criteria, including 15 745 clear cell, 1340 papillary, and 850 chromophobe RCC cases. The 5‐year OS rates for clear cell, papillary, and chromophobe RCC were 91.2%, 89.7%, and 93.5% at pStage I, and declined to 37.5%, 21.7%, and 59.3% at pStage IV, respectively. Age‐stratified analyses in pStage I disease revealed progressively worse OS with advancing age across all histological subtypes. Among patients aged ≥ 85 years, the 5‐year OS rates were 68.2% for clear cell, 50.0% for papillary, and 70.0% for chromophobe RCC. Conclusions: This nationwide registry‐based study provides updated real‐world evidence on survival patterns in RCC in Japan. Advanced age was associated with reduced OS even in patients with pStage I disease, highlighting the importance of considering age when interpreting overall survival in surgically treated patients with RCC.

Objectives: Preemptive kidney transplantation (PEKT) is known to have better outcomes than kidney transplantation (KT) after dialysis therapy. However, the effect of pretransplant dialysis duration (PTDD) on KT outcomes under good hemodialysis control remains unclear. We investigated the association between PTDD and KT outcomes in a Japanese cohort with favorable dialysis management. Methods: Among three institutions, 805 patients who underwent a living donor KT between 2001 and 2021 were enrolled in this study. Those who underwent more than one KT, multiple organ transplantations in addition to KT, or transplantations at < 20 years of age were excluded. Calcineurin inhibitors, mycophenolate mofetil, and steroids were the primary maintenance immunosuppressors. Results: The allograft survival rates of the non‐PEKT group were significantly lower than those of the PEKT group (hazard ratio [HR] 1.67, 95% confidence interval [CI] 1.04–2.70). Univariate analysis showed that ≥ 2 years of PTDD demonstrated the highest HR for allograft loss when PTDD was separated by year (95% CI 1.11–2.55). Multivariate analysis showed that ≥ 2 years of PTDD (HR 2.61 [95% CI 1.58–4.38]), being a male recipient (HR 2.35 [95% CI 1.30–4.53]), and having diabetic nephropathy (HR 2.94 [95% CI 1.71–4.98]) were suggested to be risk factors for allograft loss. Additionally, < 2 years of PTDD resulted in significantly higher allograft survival rates; the 10‐year allograft survival rates of recipients with ≥ 2 years and < 2 years of PTDD were 82.0% and 91.8%, respectively. Conclusions: Allograft survival remained unaffected when KT is performed after a short‐term dialysis introduction.

This multicenter longitudinal study was conducted across 24 institutions in Japan to examine the impact of urinary diversion on health‐related quality of life (HRQOL) among bladder cancer patients who underwent radical cystectomy (RC). We evaluated bladder cancer‐specific HRQOL and general HRQOL via the bladder cancer index (BCI) and the QOL General (QGEN‐8), respectively, before the operation and at 3, 6, and 12 months postoperatively. The scores were compared across urinary diversion groups as well as across different time points within each urinary diversion group with linear mixed‐effects models. Data from 227 patients were analyzed (151 with ileal conduits, 45 with ureterostomy, and 31 with neobladders). Neobladder patients were more likely to experience longitudinal impacts of their urinary diversion on urinary function than ileal conduit or ureterostomy patients were. Compared with that at baseline, the bowel function of neobladder patients remained impaired 12 months after surgery. All urinary diversion groups had worse sexual function scores at 3 and 6 months than at baseline, and the ileal conduit and neobladder groups had significantly worse sexual function scores at 12 months than at baseline. On the other hand, there was no significant difference in bother scores in the urinary, bowel, or sexual domain. The generic HRQOL was maintained from the preoperative to the postoperative period in all urinary diversion groups. This study explored longitudinal changes in HRQOL after RC, and the findings may help inform patient counseling regarding possible QOL trajectories.

Background: We investigated the role of pharmacists in adverse event (AE) management during renal cell carcinoma (RCC) drug therapy by surveying patients, physicians, and pharmacists. We identified the types of AEs for which pharmacist involvement is beneficial and explored measures to promote pharmacist intervention. Methods: This was an ad hoc analysis of a questionnaire-based cross-sectional web survey conducted from May to June 2022 among patients undergoing RCC drug therapy, physicians prescribing RCC treatments, and pharmacists involved in oncology care in Japan. Results: A total of 83 patients with metastatic RCC, 165 physicians, and 218 pharmacists were included. Among patients, 28.9% reported experiencing AEs or symptoms requiring pharmacist intervention. Most physicians (78.2%) and pharmacists (96.3%) supported pharmacist involvement in AE management. Notably, 35.6% of patients who reported no AEs or symptoms requiring pharmacist intervention acknowledged difficulty in communicating AEs to their physicians. Regarding desired pharmacist interventions for AEs, patients prioritized rash/pruritus, fatigue, and diarrhea; physicians emphasized stomatitis and anorexia; pharmacists identified constipation, stomatitis, and diarrhea. The most common reason patients valued pharmacist involvement was the reassurance of support from multiple healthcare providers. Physicians and pharmacists valued pharmacists’ greater familiarity with AE management, particularly considering physicians’ limited time. Raising awareness among patients and healthcare professionals, patient requests, and improving institutional support were strategies to enhance pharmacist involvement. Over 86% of healthcare professionals considered pharmaceutical outpatient clinics necessary to strengthen interdisciplinary collaboration. Conclusions: This study highlights widespread support among patients, physicians, and pharmacists for pharmacist involvement in managing AEs during RCC drug therapy.

Purpose: The prognostic significance of C-reactive protein (CRP) in clear cell renal cell carcinoma remains incompletely understood. We investigated the association between CRP levels and oncological outcomes in patients undergoing nephrectomy for localized clear cell renal cell carcinoma. Materials and Methods: A retrospective analysis was conducted using data from a Japanese multicenter database, including 1237 patients with localized clear cell renal cell carcinoma (cT1-3N0M0) who underwent radical or partial nephrectomy. Survival outcomes were assessed using the Kaplan-Meier method and Cox proportional hazards models, with restricted cubic splines used to evaluate nonlinear relationships. Results: The median follow-up duration was 39 months. Higher preoperative CRP levels were associated with increased overall mortality and risk of recurrence. Spline regression analysis demonstrated a nonlinear association between the actual CRP level and the hazard ratio of overall mortality ( P for nonlinearity = .003). In contrast, a nonlinear association between the logarithmic CRP level and the hazard ratio of overall mortality was not observed. Multivariate analysis revealed that including CRP (cutoff, 3 mg/L) resulted in the greatest improvement in the concordance index. Similarly, elevated CRP levels were associated with a higher risk of recurrence. Actual CRP levels showed a nonlinear association with the hazard ratio for recurrence risk ( P for nonlinearity < .001). Conclusions: An elevated preoperative CRP level is a significant prognostic factor for overall survival and recurrence in localized clear cell renal cell carcinoma.

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced renal cell carcinoma (RCC). However, ICIs often induce immune‐related adverse events (irAEs), which vary greatly among individuals and may influence treatment outcomes. This study aimed to identify genetic markers associated with the risk of severe treatment‐related adverse events (trAEs) and assess their impact on patient prognosis. From August 19, 2019, to September 30, 2020, patient recruitment for nivolumab treatment in advanced clear cell RCC (ccRCC) was conducted across 23 institutions in Japan, with follow‐up concluding on March 31, 2021 (protocol ID: UMIN000037739). A genome‐wide association study (GWAS) was conducted in a development cohort to identify single nucleotide polymorphisms (SNPs) associated with severe trAEs following nivolumab. Sixteen SNPs were identified, and thirteen were genotyped in a validation cohort. Eight SNPs showed consistent trends with the development cohort, but they have not reached statistical significance in the validation cohort. Among them, rs2545737, corresponding to CHD1 , was significantly linked to prolonged progression‐free survival (PFS), highlighting its potential as a biomarker for both safety and efficacy. Further analysis indicated that high CHD1 expression in tumors correlated with improved overall survival in nivolumab‐treated patients but not in those receiving everolimus. Given the failure to replicate the development set findings in our validation cohort, further re‐validation within the RCC population is warranted. However, these results enhance our understanding of the genetic predisposition to trAEs and provide a significant step toward safer and more effective cancer treatment strategies. This study was registered on the University Hospital Medical Information Network (UMIN) in Japan on August 20, 2019 (protocol ID: UMIN000037739).

Background: Avelumab + axitinib was approved for the treatment of advanced renal cell carcinoma (aRCC) in Japan in December 2019. We report long-term real-world subgroup analyses with first-line avelumab + axitinib in patients with aRCC by International Metastatic RCC Database Consortium (IMDC) risk classification from the J-DART2 study in Japan. Methods: J-DART2 was a multicenter, noninterventional, retrospective study examining characteristics, treatment patterns, and outcomes in patients with aRCC who started first-line avelumab + axitinib in Japan between December 2019 and October 2022. Results: Data from 150 patients across 19 sites were analyzed. IMDC risk was favorable in 39 patients (26.0%), intermediate (1 risk factor) in 46 (30.7%), intermediate (2 risk factors) in 36 (24.0%), and poor in 29 (19.3%). Baseline characteristics were generally consistent across IMDC risk subgroups. In subgroups with favorable, intermediate (1 risk factor), intermediate (2 risk factors), and poor risk, median progression-free survival was 31.0, 15.3, 16.4, and 8.1 months; median overall survival (OS) was not reached, but 24-month OS rates were 95.2%, 91.3%, 85.3%, and 57.6%, respectively. Objective response rates were 54.5%, 56.8%, 47.1%, and 54.2%, respectively. High-dose corticosteroid treatment for immune-related adverse events was administered in 5.1%, 8.7%, 8.3%, and 6.9% of patients, respectively. Conclusion: Subgroup analyses from J-DART2 confirm the long-term real-world effectiveness of first-line avelumab + axitinib across IMDC risk groups in patients with aRCC in Japan. Our findings were consistent with previous analyses by IMDC risk and support the favorable benefit-risk profile of avelumab + axitinib in clinical practice in Japan.

Background: Avelumab + axitinib was approved for advanced renal cell carcinoma (aRCC) in Japan in December 2019. We report long-term real-world outcomes with first-line avelumab + axitinib from the J-DART2 study in Japan. Methods: J-DART2 was a multicenter, noninterventional, retrospective study examining clinical data from patients with curatively unresectable locally advanced or metastatic RCC who started treatment with first-line avelumab + axitinib in Japan between December 2019 and October 2022. Endpoints included patient characteristics, treatment patterns, and outcomes. Results: Data from 150 patients across 19 sites were analyzed; median follow-up was 18.7 months (95% CI, 16.3–20.6 months). Median age was 70.5 years; 26.0% of patients were aged ≤64 years, 42.7% were aged 65–74 years, and 31.3% were aged ≥75 years. International Metastatic RCC Database Consortium risk was favorable in 26.0%, intermediate in 54.7% (1 risk factor in 30.7%; 2 risk factors in 24.0%), and poor in 19.3% of patients. Median progression-free survival (PFS) was 17.1 months, with 1- and 2-year PFS rates of 57.7% and 37.5%, respectively. Median overall survival (OS) was not reached, with 1- and 2-year OS rates of 90.6% and 84.7%, respectively. Objective response rate was 53.3%; disease control rate was 88.9%. Outcomes were similar across age groups, including patients aged ≥75 years. Conclusions: J-DART2 is the largest retrospective study to report long-term real-world outcomes in patients with aRCC treated with avelumab + axitinib in Japan. Findings were similar to those observed in previous studies and support the benefit of avelumab + axitinib in clinical practice in Japan.

Objective: To achieve patient‐centricity in metastatic renal cell carcinoma (mRCC) treatment, it is essential to clarify the differences in perspectives between patients and physicians. This cross‐sectional analysis of a web survey aimed to clarify the differences in expectations and concerns between mRCC patients and physicians regarding systemic mRCC therapy in Japan.Methods: Surveys from 83 patients and 165 physicians were analyzed.Results: The top three most significant differences in expectations of systemic therapy between patients and physicians (patient‐based physician value) were “Chance of achieving treatment‐free status” (−30.1%, p < 0.001), “Longer survival” (+25.8%, p < 0.001), and “Chance of eliminating all evidence of disease” (−25.6%, p < 0.001). The top three most significant differences in concerns for systemic therapy between patients and physicians (patient‐based physician value) were “Lack of efficacy” (+36.1%, p < 0.001), “Lack of knowledge of treatment” (−28.2%, p < 0.001), and “Daily activities affected by side effects” (+22.3%, p < 0.001). Diarrhea, fatigue/malaise, and nausea/vomiting were patients' most distressing adverse events; 50.6% of patients had difficulty telling their physicians about adverse events such as fatigue, anxiety, and depression.Conclusions: This study demonstrated a gap between patients with mRCC and physicians in their expectations and concerns for systemic therapy. Japanese patients with mRCC suffer from a number of adverse events, some of which are not shared with physicians. This study highlights the importance of communicating well with patients in clinical practice to achieve patient‐centricity in systemic treatment for mRCC.

Information on the financial toxicity experienced by Japanese patients with metastatic renal cell carcinoma (mRCC) is lacking, even though Japan has its own unique public health insurance system. Thus, a web-based survey was conducted to evaluate the financial toxicity experienced by Japanese mRCC patients using the COmprehensive Score for financial Toxicity (COST) tool. This study enrolled Japanese patients who underwent, or were undergoing, systemic therapy for mRCC. The outcomes evaluated were the distribution of COST scores, the correlation between COST and quality of life (QOL) assessed by the Functional Assessment of Cancer Therapy-General (FACT-G) scale, and demographic factors associated with financial toxicity. The median (range) COST score was 19.0 (3.0–36.0). The Pearson correlation coefficient for COST and FACT-G total scores was 0.40. Univariate analysis revealed that not having private health insurance and lower household income per year were significantly associated with lower COST scores. Multivariate analyses showed that age < 65 years and not having private health insurance were significantly associated with lower COST scores. This study revealed that Japanese mRCC patients experience adverse financial impacts even under the universal health insurance coverage system available in Japan, and financial toxicity negatively affects their QOL.