Masaya Ito's research while affiliated with Tokyo Metropolitan Cancer and Infectious Diseases Center and other places

Objectives To evaluate longitudinal changes in lower urinary tract symptoms (LUTS) after artificial urinary sphincter (AUS) implantation in patients undergoing radiation therapy (RT) in comparison to those in non‐irradiated patients. Methods This retrospective study included 20 and 51 patients with and without a history of pelvic RT (RT and non‐RT group, respectively) who were treated with primary AUS implantation for post‐radical prostatectomy incontinence between 2010 and 2020. Longitudinal changes in the International Consultation on Incontinence Questionnaire‐Short Form (ICIQ‐SF), the International Prostate Symptom Score (IPSS), and the Overactive Bladder Symptom Score (OABSS) were calculated with a linear mixed model. Results In the RT and non‐RT group, 18 (90%) and 48 (94%) patients achieved social continence, defined as daily pad use ≤1 at 1 month after activation of AUS, respectively ( p = .555). During the mean follow‐up of 38 months, ICIQ‐SF, IPSS, and OABSS significantly improved after AUS implantation in both the RT and non‐RT groups. In the RT group, ICIQ‐SF, IPSS, and OABSS subsequently deteriorated with a slope of 0.62/year ( p = .010), 0.55/year ( p = .025), and 0.30/year ( p = .007), respectively. In the non‐RT group, no significant longitudinal changes in subsequent IPSS and OABSS were observed, although ICIQ‐SF significantly deteriorated (0.43/year, p = .006). Comparing between the groups, the slopes of IPSS and OABSS were significantly greater in the RT group than in the non‐RT group ( p < .001, and .015, respectively). Conclusions Longitudinal deterioration in LUTS that improved immediately after AUS implantation was observed in patients with a history of pelvic RT, but not in patients without a history of pelvic RT.

Background: The BioJet system allows the fusion of magnetic resonance imaging (MRI) images with real-time transrectal ultrasonography to accurately direct biopsy needles to the target lesions. To date, the superiority of targeted biopsy using the BioJet system over cognitive registration remains unknown. Methods: This retrospective study included 171 biopsy-naïve men with elevated prostate-specific antigen (2.5-20 ng/mL) and MRI-positive lesions; 74 and 97 men underwent a four-core targeted biopsy per MRI-positive target lesion and a 14-core systematic biopsy transperineally using the BioJet system and cognitive registration, respectively. Detection rates of significant cancer, defined as grade group ≥ 2 or maximum cancer length ≥ 5 mm, were compared between the BioJet system and cognitive registration using propensity score matching and a multivariate logistic regression model. Results: After propensity score matching (67 men for each group), the detection rates of significant cancer were significantly higher in the BioJet group than in the cognitive group for both targeted (76% vs. 46%, P = 0.002) and systematic (70% vs. 46%, P = 0.018) biopsy. Multivariate analysis of the entire cohort also showed that the BioJet system was independently associated with significant cancer detection by targeted and systematic biopsy (P < 0.01), along with a higher prostate-specific antigen density and a higher prostate imaging reporting and data system score. Conclusions: Transperineal prostate biopsy using the BioJet system is superior to cognitive registration in detecting significant cancer for targeted and systematic biopsies.

Purpose To investigate whether even a minimally invasive diagnostic procedure for the upper tract such as ureteral catheterization (UCath) may substantially increase the risk of intravesical recurrence (IVR) in patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU). Methods The present, retrospective study enrolled 163 patients undergoing RNU for UTUC between 2010 and 2021 at two, tertiary care hospitals. The primary endpoint was the association between UCath and IVR-free survival (IVRFS). The secondary endpoints were the association of ureterorenoscopy (URS) and URS biopsy (URSBx) with IVRFS. Directed acyclic graph (DAG)-guided multivariable models were used to adjust for potential confounders. Results Of the 163 patients, 128 (79%), 88 (54%), and 67 (41%) received UCath, URS, and URSBx, respectively. URS was performed concurrently with UCath. During the follow-up period (median: 47 months), IVR developed in 62 patients (5-year IVRFS rate: 52%). A DAG included concurrent bladder cancer, tumour size, hydronephrosis, positive cytology, and multiple UTUCs as potential confounders of the association between UCath and IVR. Both DAG-guided and stepwise multivariable models revealed a significant association between UCath and IVR (hazard ratio: 17.8; P < 0.001). UCath was also associated with shorter IVRFS in a subset of 75 patients who had not received URS (P < 0.001). In contrast, URS and URSBx were not associated with IVR in patients who had received UCath and URS, respectively. Conclusion Any diagnostic manipulations of the upper urinary tract, even a minimally invasive procedure like UCath, could confer a risk of post-RNU IVR in UTUC patients.

Background The BioJet system allows the fusion of magnetic resonance imaging (MRI) images with real-time transrectal ultrasonography to accurately direct biopsy needles to the target lesions. To date, the superiority of targeted biopsy using the BioJet system over cognitive registration remains unknown. Methods This retrospective study included 171 biopsy-naïve men with elevated prostate-specific antigen (2.5–20 ng/mL) and MRI-positive lesions; 74 and 97 men underwent a four-core targeted biopsy per MRI-positive target lesion and a 14-core systematic biopsy transperineally using the BioJet system and cognitive registration, respectively. Detection rates of significant cancer, defined as grade group ≥ 2 or maximum cancer length ≥ 5 mm, were compared between the BioJet system and cognitive registration using propensity score matching and a multivariate logistic regression model. Results After propensity score matching (70 men for each group), the detection rates of significant cancer were significantly higher in the BioJet group than in the cognitive group for both targeted (76% vs. 51%, P = 0.007) and systematic (70% vs. 46%, P = 0.005) biopsy. Multivariate analysis of the entire cohort also showed that the BioJet system was independently associated with significant cancer detection by targeted and systematic biopsy (P < 0.01), along with a higher prostate-specific antigen level, a lower prostate volume, and a higher prostate imaging reporting and data system score. Conclusions Transperineal prostate biopsy using the BioJet system is superior to cognitive registration in detecting significant cancer for targeted and systematic biopsies.

Background The significance of metastasis-directed therapy for oligometastatic prostate cancer has been widely discussed, and targeted therapy for progressive sites is a feasible option as a multidisciplinary treatment for castration-resistant prostate cancer (CRPC). When oligometastatic CRPC with only bone metastases progresses after targeted therapy, it tends to progress as multiple bone metastases. The progression of oligometastatic CRPC after targeted therapy may be due in part to the presence of micrometastatic lesions that, though undetected on imaging, were present prior to targeted therapy. Thus the systemic treatment of micrometastases in combination with targeted therapy for progressive sites is expected to enhance the therapeutic effect. Radium-223 dichloride (radium-223) is a radiopharmaceutical that selectively binds to sites of increased bone turnover and inhibits the growth of adjacent tumor cells by emitting alpha rays. Therefore, for oligometastatic CRPC with only bone metastases, radium-223 may enhance the therapeutic effect of radiotherapy for active metastases. Methods This phase II, randomized trial of Metastasis-Directed therapy with ALpha emitter radium-223 in men with oligometastatic CRPC (MEDAL) is designed to assess the utility of radium-223 in combination with metastasis-directed radiotherapy in patients with oligometastatic CRPC confined to bone. In this trial, patients with oligometastatic CRPC with three or fewer bone metastases on whole-body MRI with diffusion-weighted MRI (WB-DWI) will be randomized in a 1:1 ratio to receive radiotherapy for active metastases plus radium-223 or radiotherapy for active metastases alone. The prior use of androgen receptor axis-targeted therapy and prostate-specific antigen doubling time will be used as allocation factors. The primary endpoint will be radiological progression-free survival against progression of bone metastases on WB-DWI. Discussion This will be the first randomized trial to evaluate the effect of radium-223 in combination with targeted therapy in oligometastatic CRPC patients. The combination of targeted therapy for macroscopic metastases with radiopharmaceuticals targeting micrometastasis is expected to be a promising new therapeutic strategy for patients with oligometastatic CRPC confined to bone. Trial registration Japan Registry of Clinical Trials (jRCT) (jRCTs031200358); Registered on March 1, 2021, https://jrct.niph.go.jp/latest-detail/jRCTs031200358

Introduction: Whole-liver radiotherapy (WLRT) is performed for palliative purposes in patients with metastatic liver tumors. However, it remains unclear whether the benefits obtained from WLRT surpass the potential disadvantages of radiotherapy-induced liver disease in such patients, particularly those with severe liver damage. We present the case of a 76-year-old man with diffuse liver metastases from castration-resistant prostate cancer. Case Report: He was diagnosed as having prostate cancer with multiple metastases to the bone, pleura, and para-aortic lymph nodes three years and six months earlier and developed hepatic metastases following a sequence of therapies, including surgical castration, bicalutamide, enzalutamide, and 10 cycles of docetaxel. Despite administering abiraterone acetate for two months, the prostate-specific antigen (PSA) levels increased, and the patient developed symptomatic liver damage, presenting with jaundice, anorexia, and fatigue. His serum total bilirubin (9.5 mg/dL) and liver transaminase (>100 U/L) levels were markedly elevated. The patient received WLRT at 8 Gy in a single fraction for palliative intent. Symptomatic relief was achieved shortly after WLRT, and the total bilirubin and transaminase levels decreased and normalized within two months. Additionally, two months after WLRT, the PSA level decreased from 285 to 23.3 ng/mL, and a robust partial tumor response was observed on computed tomography images. Although the patient died of cancer eight months after WLRT, radiotherapy-induced liver disease was not confirmed during the follow-up period. Conclusion: In the present case, WLRT successfully relieved the symptoms and reversed the liver damage caused by diffuse metastases, and it was considered to contribute to cancer control without adverse events. Thus, WLRT can be a viable option for patients with liver damage induced by diffuse liver metastases.

Background: While the controlling nutritional status (CONUT) score and sarcopenia are objective indices of different aspects of a patient's general condition, few studies have comprehensively examined their mutual relationship in patients with advanced cancer. Methods: This retrospective study included 200 Japanese patients with advanced urothelial carcinoma (aUC). Sarcopenia was diagnosed using Prado's definition. The CONUT score and sarcopenia were examined for their possible association, and their prognostic value was analyzed. Results: The CONUT score and sarcopenia were not significantly associated. While sarcopenia occurred in 168 patients (84%), more than half of them had normal or only slightly impaired nutritional status, as indicated by a CONUT score of 0-2. During follow-up (median: 13.3 months), 149 patients died. The CONUT score and sarcopenia were independent prognostic factors (hazard ratio 1.22 and 2.23, respectively; both p < 0.001), whereas performance status was not. Incorporating the CONUT score, sarcopenia, and both into Bajorin's and Apolo's prognostic models increased their concordance index as follows: 0.612 for Bajorin's original model to 0.653 (+the CONUT score), 0.631 (+sarcopenia), and 0.665 (+both), and 0.634 for Apolo's original model to 0.655 (+the CONUT score), 0.653 (+ sarcopenia), and 0.668 (+both). Conclusion: The CONUT score and sarcopenia were mutually independent in terms of their prognostic value in patients with aUC. These objective indices of a patient's general condition may help in decision-making when considering treatment for patients with aUC.

Background: We hypothesized that diagnostic ureterorenoscopy (URS) may adversely affect prognosis in a subset of patients with high-risk upper tract urothelial carcinoma (UTUC) undergoing radical nephroureterectomy (RNU). Methods: The present retrospective study included 143 patients with UTUC treated between 2010 and 2021 at two tertiary care hospitals, of whom 79 received URS prior to RNU. Subgroups were stratified by clinicopathological variables relevant to prognosis. The primary endpoint was to evaluate the prognostic impact of URS on overall survival (OS) and progression-free survival (PFS) after RNU. Results: During follow-up (median 54 months for survivors), 32 cases of all-cause mortality and 40 cases of progression were recorded. No significant difference was found in OS or PFS between patients with and without URS. Subgroup analysis demonstrated that URS was significantly associated with worse OS (p < 0.001) and PFS (p = 0.008) in 29 patients with non-papillary and ≥pT3 UTUC. Importantly, URS did not have any adverse effects on prognosis in 62 patients with papillary and ≤pT2 UTUC (p = 0.005). Conclusions: URS may adversely affect prognosis of UTUC patients, specifically non-papillary and ≥pT3 disease. URS may better be avoided in patients with high-risk UTUC features unless URS is necessary to diagnose UTUC. This study also corroborates the oncological safety of URS in those with low-risk UTUC.

Objective To develop preoperative models as a guide to indications for neoadjuvant chemotherapy (NAC) and regional lymph node dissection (LND) before and at radical nephroureterectomy (RNU), respectively, in patients with non-metastatic upper tract urothelial carcinoma (UTUC) by incorporating the systemic immune-inflammation index (SII).Methods This retrospective study enrolled 103 consecutive patients with UTUC undergoing RNU. The SII was calculated as neutrophils × platelets / lymphocytes. Multivariable Cox proportional hazard model was used to develop preoperative models for cancer-specific survival (CSS) and overall survival (OS). A model for predicting muscle invasion was developed using logistic regression analysis. Harrell's concordance-index (c-index) or the area under the receiver operating characteristic curve (AUC) was used to evaluate the accuracy of the models.ResultsDuring follow-up (median: 41 months), 26 and three patients died of UTUC and other causes, respectively. Performance status > 0, clinical tumor (cT) stage ≥ 3, and SII > 520 were independent adverse prognosticators for CSS, and one point was assigned to each prognosticator. Risk score models comprising the sum of the points stratified patients into three risk groups (0, 1, and 2–3; P < 0.001 for CSS and OS) with respective c-indices of 0.843 and 0.820. SII > 677 and ≥ cT3 were independently associated with muscle invasion. A model based on these variables predicted muscle invasion with AUC of 0.804.Conclusion Preoperative SII is significantly associated with worse survival outcomes and muscle invasion in patients with non-metastatic UTUC. Our preoperative predictive models may serve as a guide to indications for NAC and LND.

Background: Reports on the prognostic significance of serum γ-glutamyltransferase (GGT) in men with metastatic castration-resistant prostate cancer (mCRPC) are limited. In addition, GGT expression status in cancer tissues has not been well characterized regardless of cancer types. Methods: This retrospective study included 107 consecutive men with mCRPC receiving docetaxel therapy. The primary endpoints were associations of serum GGT with overall survival (OS) and prostate-specific antigen (PSA) response. The secondary endpoint was an association of serum GGT with progression-free survival (PFS). Additionally, GGT expression status was immunohistochemically semi-quantified using tissue microarrays. Results: A total of 67 (63%) men died during follow-up periods (median 22.5 months for survivors). On multivariable analysis, high Log GGT was independently associated with adverse OS (HR 1.49, p = 0.006) as were low hemoglobin (HR 0.79, p = 0.002) and high PSA (HR 1.40, p < 0.001). In contrast, serum GGT was not significantly associated with PSA response or PFS. Moreover, incorporation of serum GGT into established prognostic models (i.e., Halabi and Smaletz models) increased their C-indices for predicting OS from 0.772 to 0.787 (p = 0.066) and from 0.777 to 0.785 (p = 0.118), respectively. Furthermore, there was a positive correlation between serum and tissue GGT levels (ρ = 0.53, p = 0.003). Conclusions: Serum GGT may be a prognostic biomarker in men with mCRPC receiving docetaxel therapy. GGT overexpression by prostate cancer cells appears to be responsible for the elevation of GGT in the serum.