Noboru Nakaigawa

Purpose To evaluate the efficacy and safety of triplet therapy in patients with metastatic hormone-sensitive prostate cancer (mHSPC), focusing on older adults, in a real-world clinical setting. Methods In this retrospective, single-center study, we analyzed data from 21 patients with mHSPC (median age: 71 years) treated with androgen deprivation therapy (ADT), docetaxel, and darolutamide. Relative (≥ 90% reduction from baseline) and absolute (PSA < 0.2 ng/mL) prostate-specific antigen (PSA) response rates over 6 months were assessed, along with adverse event (AE) profiles. Results At 6 months, the absolute PSA response rate was 71.4%, while the relative PSA response rate reached 100% by 3 months. Treatment-related toxicity was notable, with AEs observed in 95.2% of the patients, predominantly neutropenia. Patients aged ≥ 80 years had significantly higher treatment interruption rates for both docetaxel and darolutamide compared with those aged ≤ 79 years. Nonetheless, PSA response rates were comparable between the age groups. Neutrophil recovery time was significantly prolonged in patients aged ≥ 80 years compared to those aged ≤ 79 years. Conclusion Triplet therapy effectively reduces PSA in patients with mHSPC, including older adults. However, the high incidence of severe AEs, particularly in older adults, underscores the need for individualized treatment strategies. Despite these challenges, careful management of toxicities makes this regimen viable in clinical practice. These findings emphasize the importance of real-world data in optimizing therapy for aging populations and may serve as a basis for future prospective studies comparing triplet and doublet therapies across diverse patient cohorts.

Background/Objectives: Our aim was to compare the complication rates of different embolization materials (absolute ethanol and gelatin sponges) used for combined transarterial embolization (TAE) and to investigate the impact of tumor size on operative time and cryoneedle use during percutaneous cryoablation (PCA). Methods: We treated 27 patients (9 women and 18 men; mean age, 74 years) with 28 early-stage (T1a) renal cell carcinoma (RCC) lesions using combined TAE and PCA between September 2018 and January 2021. During TAE, 15 lesions in 14 patients were embolized using mixed absolute ethanol and iodized oil. The remaining 13 lesions (in 13 patients) were embolized using a gelatin sponge followed by iodized oil. The PCA was performed within 3 to 21 days of the TAE. We compared complications between the TAE subgroups (i.e., absolute ethanol and gelatin sponge) and assessed potential correlations between tumor size and the operative time of the PCA. Results: All patients were successfully treated by combined TAE-PCA. Local control was achieved for all patients (monitoring period, 1–48 months; median, 28 months). Although the effect of TAE did not differ between subgroups, a significantly higher number of patients in the absolute ethanol group experienced intraprocedural pain than in the gelatin sponge group (p < 0.05). The operative time of the PCA was significantly correlated with the size of the RCC lesion (p < 0.01). The number of cryoneedles used for the PCA was also correlated with the size of the RCC lesion (p < 0.0001). Conclusions: For TAE prior to PCA for early-stage RCC, gelatin sponges can replace absolute ethanol to reduce intraprocedural pain. Tumor size correlates with operative time and the number of cryoneedles needed for PCA, which suggests the total medical cost for PCA therefore varies based on the tumor’s size.

PET/CT imaging with Zirconium-89 labeled [⁸⁹Zr]Zr-DFO-girentuximab, which targets tumor antigen CAIX, may aid in the differentiation and characterization of clear cell renal cell carcinomas (RCC) and other renal and extrarenal lesions, and has been studied in European and American cohorts. We report results from a phase I study that evaluated the safety profile, biodistribution, and dosimetry of [⁸⁹Zr]Zr-DFO-girentuximab in Japanese patients with suspected RCC. Eligible adult patients received 37 MBq (± 10%; 10 mg mass dose) of intravenous [⁸⁹Zr]Zr-DFO-girentuximab. Safety and tolerability profile was assessed based on adverse events, concomitant medications, physical examination, vital signs, hematology, serum chemistry, urinalysis, human anti-chimeric antibody measurement, and 12-lead electrocardiograms at predefined intervals. Biodistribution and normal organ and tumor dosimetry were evaluated with PET/CT images acquired at 0.5, 4, 24, 72 h and Day 5 ± 2 d after administration. [⁸⁹Zr]Zr-DFO-girentuximab was administered in six patients as per protocol. No treatment-emergent adverse events were reported. Dosimetry analysis showed that radioactivity was widely distributed in the body, and that the absorbed dose in healthy organs was highest in the liver (mean ± standard deviation) (1.365 ± 0.245 mGy/MBq), kidney (1.126 ± 0.190 mGy/MBq), heart wall (1.096 ± 0.232 mGy/MBq), and spleen (1.072 ± 0.466 mGy/MBq). The mean effective dose, adjusted by the radioactive dose administered, was 0.470 mSv/MBq. The radiation dose was highly accumulated in the targeted tumor, while any abnormal accumulation in other organs was not reported. This study demonstrates that [⁸⁹Zr]Zr-DFO-girentuximab administered to Japanese patients with suspected RCC has a favorable safety profile and is well tolerated and has a similar dosimetry profile to previously studied populations.

Objective: Radical prostatectomy can be performed more safely and with fewer com- plications since the advent of robot-assisted surgery. However, increased bleeding is a concern when robot-assisted radical prostatectomy includes lymph node dissection and nerve sparing. In real-world clinical practice, inexperienced surgeons sometimes perform robot-assisted radical prostatectomy. In this study, we investigated the effec- tiveness of microporous polysaccharide hemospheres as a local hemostatic agent in robot-assisted radical prostatectomy. Methods: We retrospectively evaluated 301 patients who underwent robot-assisted radical prostatectomy at our institution between December 2017 and November 2020. The patients were divided into 2 groups according to whether their surgery was per- formed after the introduction of microporous polysaccharide hemospheres as a local hemostatic agent (group A, n = 140) or before it (group B, n = 161: historical control). Results: Preoperative androgen deprivation therapy was significantly more common in group A than in group B (23 vs. 11, P = .009). Furthermore, surgeons were significantly less experienced (P < .001) and the operation time was significantly longer (260 min- utes vs. 229 minutes; P < .001) in group A than in group B. There was no significant difference in any other patient background characteristics or in the surgical outcomes between the groups. Conclusion: The use of microporous polysaccharide hemospheres allowed even inex- perienced surgeons to perform robot-assisted radical prostatectomy without compro- mising surgical outcomes. Cite this article as: Nirei T, Tatenuma T, Muraoka K, et al. Real-world data on the effectiveness of microporous polysaccharide hemospheres for allowing even novice surgeons to perform robot-assisted radical prostatectomy safely. Urol Res Pract. 2023;49(4):241-245.

Background: Nivolumab plus ipilimumab combination therapy is one of the standard therapies for untreated renal cell carcinoma patients with an International Metastatic Renal Cell Carcinoma Database Consortium intermediate/poor risk. We have previously reported the 1-year analysis results of the effectiveness and safety of nivolumab plus ipilimumab combination therapy in the real-world setting in Japan. Here, we report the effectiveness of nivolumab plus ipilimumab combination therapy and of second-line therapy, using 2-year analysis. Methods: This retrospective observational study enrolled Japanese patients with previously untreated metastatic renal cell carcinoma who initiated nivolumab plus ipilimumab combination therapy between August 2018 and January 2019. Data were collected from patients’ medical records at baseline and at 3 months, 1 year and 2 years after the last enrollment. Results: Of the 45 patients enrolled, 10 patients (22.2%) each had non-clear cell renal cell carcinoma and Eastern Cooperative Oncology Group performance status ≥2 at baseline. Median follow-up period was 24.0 months; objective response rate was 41.5%, with 6 patients achieving complete response; median progression-free survival was 17.8 months and 24-month progression-free survival and overall survival rates were 41.6 and 59.1%, respectively. Second-line therapy achieved an objective response rate of 20%; median progression-free survival was 9.8 months. Median progression-free survival 2 was 26.4 months. Conclusions: The effectiveness of nivolumab plus ipilimumab combination therapy at 2-year analysis in the real-world setting in Japan was comparable to that reported in CheckMate 214. The current analysis also demonstrated the effectiveness of second-line therapy after nivolumab plus ipilimumab combination therapy.

Tissue assays have improved our understanding of cancers in terms of the three-dimensional structures and cellular diversity of the tissue, although they are not yet well-developed. Perfusion culture and active chemical gradient formation in centimeter order are difficult in tissue assays, but they are important for simulating the metabolic functions of tissues. Using microfluidic technology, we developed an H-shaped channel device that could form a long concentration gradient of molecules in a tissue that we could then analyze based on its appearance and content. For demonstration, a cylindrical pork tissue specimen was punched and equipped in the H-shaped channel device, and both ends of the tissue were exposed to flowing distilled and blue-dyed water for 100 h. After perfusion, the tissue was removed from the H-shaped channel device and sectioned. The gradient of the blue intensity along the longitudinal direction of the tissue was measured based on its appearance and content. We confirmed that the measured gradients from the appearance and content were comparable.

Background: Human epididymis protein 4 (HE4) has been indicated as a novel tumor marker for ovarian cancer diagnosis/monitoring and as a mediator of renal fibrosis. In this study, we investigated the potential role of HE4 in the pathogenesis of patients with renal cell carcinoma (RCC). Methods: We retrospectively enrolled 249 patients with RCC who underwent nephrectomies at a single center between 1997 and 2010. HE4 expression was evaluated by immunohistochemistry and RNA in situ hybridization staining in both tumor and renal cortex tissue microarrays. The expression of HE4 was evaluated in line with the clinicopathologic features of each patient. Results: HE4-positive staining was confirmed in 37 (15.0%) tumor tissue microarrays and in 88 (38.3%) cortex tissue microarrays. High expression of HE4 in the tumor was not associated with overall survival (OS), cancer-specific survival (CSS), or recurrence free survival (RFS). However, high expression of HE4 in the renal cortex was strongly associated with an increased risk of OS, CSS, and RFS (HR 3.608 (95% confidence interval (CI) 2.127-6.118); pConclusions: High expression of HE4 in the renal cortex is an independent risk factor of OS and CSS in RCC. Further investigations are needed to elucidate the underlying mechanisms of HE4 in the renal cortex in the progression of renal cell carcinoma.

Purpose Nivolumab is part of the standard therapy for mRCC. Although deep and long-lasting responses are seen in some patients, the benefit of treatment is limited to some patients and the majority of patients will experience disease progression. PD-L1 is still under evaluation as a predictive biomarker and there is an urgent need to establish biomarkers for the treatment of nivolumab. Here, we investigate C-reactive protein (CRP) at 1 month after treatment of nivolumab as a target to predict the response of patients with metastatic renal cell carcinoma (mRCC) to nivolumab. Methods After approval of the study by our institutional review board, 64 patients with mRCC who underwent nivolumab treatment at Kanagawa Cancer Center and Yokohama City University Hospital were enrolled. The patient characteristics, blood examination data at start of nivolumab treatment and 1 month after treatment, response to treatment and progression-free survival (PFS) were evaluated. Tumour responses were assessed according to both the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and the immune RECIST (iRECIST) criteria. Moreover, in 12 patients who agreed to an additional blood examination, several serum inflammatory factors were investigated and their correlation with CRP level was examined. Results The median follow-up was 8.3 months (range 0.2–29.8 months). The median PFS period was 4.5 months and the median immune-PFS (iPFS) period was 5.3 months. RECIST 1.1 criteria underestimated the benefits of nivolumab in four (6.4%) cases. Multivariate analyses showed that an Eastern Cooperative Oncology Group performance status (≥ 2) at start of treatment and CRP level at 1 month after treatment (≥ 1.5 mg/dL) were independent risk factors for a poor iPFS of nivolumab. The CRP level at baseline was not an independent prognostic factor for iPFS. When compared with the responder group (iCR + iPR + iSD), the non-responder group (iPD) had a significantly higher CRP levels at 1 month after treatment (p < 0.001). In the responder group, there was significant decrease in the CRP level after nivolumab treatment when compared with the baseline (p = 0.002), whereas there was a significant increase in the non-responder group (p = 0.019). Even patients with high baseline CRP (≥ 1.5 mg/dL) obtained good iPFS if CRP was decreased (< 1.5 mg/dL) 1 month after treatment. In addition, the classification of Glasgow prognostic score (GPS), which is a cumulative prognostic score based on CRP and albumin, was a significant predictor for iPFS. A strong correlation (|r| > 0.7) with CRP level at 1 month after treatment was seen for sCD163, IL-34, MMP-1, MMP-2, osteopontin, sTNF-R1 and sTNF-R2. Of these, MMP-1 and MMP-2 were not correlated at baseline. Conclusion Our results indicated that the CRP level at 1 month after treatment with nivolumab appears to be a promising predictive biomarker for response to nivolumab treatment in patients with mRCC. It is clinically useful to be able to predict the effect within a short period. Further prospective trials are needed to prove these preliminary findings.