Fumiya Hongo

Objectives: Cabozantinib treatment is associated with improved survival in renal cell carcinoma (RCC) patients with bone metastasis. We evaluated the direct effects of cabozantinib on bone metastasis in advanced RCC (aRCC). Methods: In this multicenter, open‐label study, adult Japanese aRCC patients with bone metastasis received oral cabozantinib 60 mg once daily until drug discontinuation/data cut‐off. The primary endpoint was the objective response rate (ORR) of bone target lesions (modified MD Anderson criteria) evaluated by an independent radiology committee. Secondary endpoints were overall survival (OS), disease control rate (DCR) of bone lesions, progression‐free survival (PFS), symptomatic skeletal events (SSEs), bone‐specific PFS, and safety. Exploratory endpoints were changes in bone turnover, plasma biomarkers, and health‐related quality of life (HRQoL). Results: Thirty‐one patients were enrolled (median age, 70.0 years; 64.5% men). The ORR of bone target lesions was 6.5% (90% CI 1.2–18.9), DCR was 90.3% (90% CI 76.8–97.3), and the median change in bone target lesion size was −5.2% (range−42.8 to 19.2). Median PFS was 11.9 months (95% CI 5.7–not evaluable), median OS was 24.9 months (95% CI 19.1–not evaluable), and three patients reported SSEs. Bone‐specific PFS remained > 60% among patients who were evaluable during follow‐up. Levels of bone‐turnover markers generally decreased; no trends were observed in plasma biomarkers. EQ‐5D‐5L index values remained generally stable. Common adverse events were palmar‐plantar erythrodysesthesia syndrome (54.8%), malaise (45.2%), diarrhea, abnormal hepatic function (32.3%), and hypertension (32.3%). Conclusions: Most aRCC patients showed favorable disease control following cabozantinib treatment. No new safety issues were observed. Trial Registration: Japan Registry of Clinical Trials (JRCT), registration no. jRCTs031210220

Objective: In addition to pathological diagnosis, the identification of a diagnostic index to determine indolent and index cancers will be useful for prostate cancer diagnosis. The present study aimed to provide evidence that quantification of DNA methylation levels at specific gene positions can serve as an indicator for the diagnosis of prostate cancer malignancy. Methods: First, we attempted to identify genomic positions where cancer cells could be discriminated from normal cells using prostate‐derived cultured cells by quantification of DNA methylation levels with methylation‐specific PCR (MSP). Using needle biopsy tissue from patients with prostate cancer bisected by a tissue divider, we quantified DNA methylation levels at four candidate loci identified in cultured cells and analyzed the pathology. Finally, we examined the correlation between DNA methylation levels and gene expression levels in nearby genomic regions using identical tissue from patients with prostate cancer. Results: Quantitative analysis using prostate‐derived cultured cells and needle biopsy tissue from prostate cancer patients showed that DNA methylation levels at CpG sites near four genes ( BCAT1 , C3orf37 , PCDHA1 ‐8, and RAI1 ) were significantly higher in cancer than in normal. In particular, DNA methylation levels near the C3orf37 gene were higher in high‐grade cancers compared to intermediate‐grade cancers, showing a significant correlation with cancer grade. In addition, a correlation tendency between DNA methylation levels and gene expression levels was found at the PCDHA1 locus among the four genetic loci. Conclusions: Quantitative analysis of DNA methylation at CpG sites near the C3orf37 gene appears to be a promising approach to distinguish between index and indolent prostate cancer cells.

Objectives: We aimed to evaluate the long‐term oncological and functional outcomes after robot‐assisted partial nephrectomy (RAPN) for renal hilar tumors. Methods: A total of 22 academic hospitals in Japan participated in a prospective, multicenter, single‐arm, open‐label trial with a 2‐year enrollment period. After undergoing RAPN, 105 patients with clinical T1 renal hilar tumors were followed up for 5 years and evaluated. Recurrence‐free survival, overall survival, and trends of renal function were set as oncological and functional outcomes. Results: Five‐year overall survival and recurrence‐free survival were 98.0% and 89.2%, respectively. Mean estimated glomerular filtration rates (eGFRs) were 69.031 mL/min preoperatively, and were 59.374, 58.334, 58.221, 56.975, and 59.602 mL/min at 1, 2, 3, 4, and 5 years after surgery, respectively. While eGFR was significantly lower than the preoperative one at all points ( p < 0.001), eGFRs at 1 and 5 years after surgery did not differ significantly ( p = 0.793). Conclusion: After long‐term follow‐up, RAPN for clinical T1 renal hilar tumors continues to provide functional and oncological outcomes equivalent to those in the perioperative period. Trial Registration: The study protocol was registered in the Japan Registry of Clinical Trials (jRCT1052190005, UMIN000023968)

Introduction: Although not frequent, the recurrence of seminoma later than 5–10 years after orchiectomy has been reported. We report a case of recurrence of seminoma 48 years after orchiectomy, with metastasis to the para‐aorta that was treated with chemotherapy.Case presentation: An 83‐year‐old man had an incidentally enlarged para‐aortic lymph node noted on computed tomography. Needle biopsy revealed metastasis from a seminoma that had been treated with orchiectomy at age 35. Chemotherapy was introduced but discontinued after the first course due to side effects. However, a decrease in fluorodeoxyglucose accumulation on positron emission tomography was observed, with no subsequent re‐enlargement of the tumor.Conclusion: Chemotherapy was introduced for an elderly patient with the longest known late relapse. Dose reduction should be considered in cases with good prognosis, considering factors such as age.

Objectives: To assess the validity of magnetic resonance imaging‐determined tumor contact area (MRI‐TCA) as a predictive factor for pathological extraprostatic extension (EPE) in cT2N0M0 prostate cancer patients. Methods: We retrospectively analyzed 72 cT2N0M0 prostate cancer patients who underwent multiparametric MRI (mpMRI) followed by robot‐assisted laparoscopic prostatectomy (RARP) between February 2014 and April 2021. Patients whose MRI‐based index lesion did not match the pathological specimens were excluded. MRI‐TCA was approximated using an elliptical shape and calculated by two different methods: MRI‐TCA1: Calculated using the tumor contact length (TCL) in the axial plane and the longer TCL in either the sagittal or coronal plane, capturing tumor dimensions across two planes. MRI‐TCA2: Calculated using the TCL in the axial plane and tumor thickness derived from MRI slice data, reflecting the tumor’s contact area within the MRI volume. We compared postoperative prostate‐specific antigen (PSA) recurrence‐free survival by stratifying patients based on the optimal thresholds of MRI‐TCL, MRI‐TCA1, MRI‐TCA2, pathological‐TCL, and pathological‐TCA. Results: Sixteen patients (22.2%) were pathologically positive for EPE. MRI‐TCL, MRI‐TCA1, and MRI‐TCA2 were significantly greater in patients with EPE‐positive (EPE+) tumors than in those with EPE‐negative (EPE−) tumors ( p < 0.0001, p < 0.0001, and p = 0.0026, respectively). No statistically significant differences were found between MRI‐TCL and MRI‐TCA1 ( p = 0.914) or between MRI‐TCL and MRI‐TCA2 ( p = 0.112) in predicting pathological EPE. A significant difference in postoperative PSA recurrence rate was observed in the stratified analysis based on pathological‐TCA ( p = 0.022). Conclusion: Both MRI‐TCA1 and MRI‐TCA2 are clinically accessible and effective parameters for predicting pathological EPE in cT2N0M0 prostate cancer patients. However, neither method demonstrated clear superiority over MRI‐TCL. Pathological‐TCA was shown to be a significant predictor of both pathological EPE and postoperative PSA recurrence.

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.

Introduction: Radical cystectomy for patients who previously underwent both radical prostatectomy and prostatic bed radiation is technically challenging.Case presentation: A 78‐year‐old man with a history of radical prostatectomy and salvage radiation for prostate cancer was referred to our hospital for radical treatment of bladder cancer. After two cycles of neoadjuvant chemotherapy, he underwent robot‐assisted radical cystectomy with real‐time transrectal ultrasound guidance during dissection of the rectovesical space to minimize the risk of rectal injury. There were no perioperative adverse events.Conclusion: Intraoperative real‐time transrectal ultrasound guidance could assist surgeons to safely perform the dissection of the rectovesical space in the surgically high‐risk patient.

Advances in immunosuppressive therapy and postoperative management have greatly improved the graft and patient survival rates after kidney transplantation; however, the incidence of post‐transplant malignant tumors is increasing. Post‐renal transplantation malignant tumors are associated with renal failure, immunosuppression, and viral infections. Moreover, the risk of developing cancer is higher in kidney transplant recipients than in the general population, and the tendency to develop cancer is affected by the background and environment of each patient. Recently, cancer after kidney transplantation has become the leading cause of death in Japan. Owing to the aggressive nature and poor prognosis of genitourinary malignancies, it is crucial to understand their epidemiology, risk factors, and best practices in kidney transplant recipients. This review has a special emphasis on the epidemiology, risk factors, and treatment protocols of genitourinary malignancies in kidney transplant recipients to enhance our understanding of the appropriate management strategies. Optimal immunosuppressive therapy and cancer management for these patients remain controversial, but adherence to the general guidelines is recommended.