The Benefits of Adjuvant Chemotherapy for Upper Tract Urothelial Carcinoma Require at Least Three Cycles.

Background: Upper urinary tract urothelial carcinoma (UTUC) is uncommon. In advanced cases, radical nephroureterectomy (RNU) alone is not curative, and recurrence and metastasis are likely to occur. Adjuvant chemotherapy (AC) is an evidence-based treatment. However, the optimal number of AC cycles is not clear. This multicenter study investigated the number of cycles required for the beneficial effects of AC in Japanese patients with UTUC. Methods: Patients who were diagnosed with UTUC and underwent RNU at our hospital and affiliated hospitals from January 2010 to September 2020 were included in the study. Patients with pathological T3 or higher or lymph node metastasis were observed or given AC, and their responses were compared. The AC regimens included gemcitabine and cisplatin or carboplatin. Patients were also classified into two groups: the observation and two cycles of AC group and the three to four cycles of AC group. The survival curves for recurrence-free survival (RFS) and cancer-specific survival (CSS) were evaluated using Kaplan-Meier analyses. Results: Of the 133 patients enrolled in the study, 24 received 2 cycles of AC, 37 received 3-4 cycles, and 72 were observed only. The 5-year RFS was 67.1% for the 3-4 cycles of AC group and 41.7% for the observation and two cycles of AC group. The 5-year CSS was 72.2% for the 3-4 cycles of AC group and 35.9% for the observation and two cycles of AC group. RFS and CSS were significantly longer in the 3-4 cycles of AC group compared to the observation and 2 cycles group (P = 0.048 and P = 0.005 respectively). Conclusion: AC prolonged RFS and CSS in the real-world setting. However, at least three cycles of AC are required to achieve beneficial effects in patients with UTUC.

Excellent Response to 177Lu-DOTATATE Peptide Receptor Radionuclide Therapy in a Patient with Treatment-Related Neuroendocrine Prostate Cancer with Urinary Retention and Rectal Obstruction: A Case Report.

Treatment-related neuroendocrine prostate cancer (tNEPC) occurs after androgen deprivation therapy and has a poor prognosis; however, there are few effective treatments for tNEPC. Therefore, tNEPC management is often challenging. This is a case of a 65-year-old Asian male patient with prostate adenocarcinoma who had metastases at initial presentation. After prostate biopsy revealed neuroendocrine prostate cancer (NEPC), he was treated with platinum-based systemic chemotherapy followed by pembrolizumab treatment. The primary tumor regions temporarily regressed, but progression of the primary tumor resulted in urinary retention and rectal obstruction; therefore, a transverse colostomy was performed, and a urethral catheter was inserted. Following somatostatin receptor scintigraphy (SRS), it was determined that the primary tumor expressed somatostatin receptors. Based on these results, treatment with 177Lu-DODATATE peptide receptor radionuclide therapy was prescribed. Subsequently, the primary tumor regressed remarkably, and the urethral catheter was removed. 177Lu-DOTATATE peptide receptor radionuclide therapy may be an effective option for tNEPC, which has few effective treatment options.

Japanese expert consensus on the standardization of robot-assisted pelvic lymph node dissection in urological surgery: Extent of pelvic lymph node and surgical technique.

Pelvic lymph node dissection (PLND) is important for accurate staging and prognosis of prostate and/or bladder cancer. Several guidelines recommend extended PLND for patients with these cancers. However, the therapeutic benefits of extended PLND are unclear. One major reason is that the extent of PLND is not clearly defined. Thus, the working group for standardization of robot-assisted PLND, including nine experienced urologists for PLND in Japan, was launched in January 2023 by the Japanese Society of Endourology and Robotics. This study summarized the discussions to define the individual extent of PLND in urological surgery in a consensus meeting among these experienced urologists. The consensus meeting determined the extent of PLND based on arteries (veins) and anatomical membrane structures rather than a vague concept or approach toward PLND. This concept is expected to allow surgeons to implement the same extent of PLND. Finally, after a total of 10 online web conferences were held, we determined the extent of PLND for the obturator lymph node (LN) area, the internal iliac LN area, the external and common iliac LN area, and the presacral LN area according to the above rules. The extent of PLND suggested here currently does not have a clear therapeutic rationale. Therefore, the extent of our proposed PLND is by no means mandatory. We hope our definition of the extent of PLND will be supported by further evidence of therapeutic benefits for urologic cancers.

Efficacy of robot-assisted partial nephrectomy compared to conventional laparoscopic partial nephrectomy for completely endophytic renal tumor: a multicenter, prospective study.

BACKGROUND: This study aimed to compare the efficacy of robot-assisted partial nephrectomy for completely endophytic renal tumors with the reported outcomes of conventional laparoscopic partial nephrectomy and investigate the transition of renal function after robot-assisted partial nephrectomy. METHODS: We conducted a prospective, multicenter, single-arm, open-label trial across 17 academic centers in Japan. Patients with endophytic renal tumors classified as cT1, cN0, cM0 were included and underwent robot-assisted partial nephrectomy. We defined two primary outcomes to assess functional and oncological aspects of the procedure, which were represented by the warm ischemic time and positive surgical margin, respectively. Comparisons were made using control values previously reported in laparoscopic partial nephrectomy studies. In the historical control group, the warm ischemia time was 25.2, and the positive surgical margin was 13%. RESULTS: Our per-protocol analysis included 98 participants. The mean warm ischemic time was 20.3 min (99% confidence interval 18.3-22.3; p < 0.0001 vs. 25.2). None of the 98 participants had a positive surgical margin (99% confidence interval 0-5.3%; p < 0.0001 vs. 13.0%). The renal function ratio of eGFR before and after protocol treatment multiplied by splits was 0.70 (95% confidence interval: 0.66-0.75). Factors such as preoperative eGFR, resected weight, and warm ischemic time influenced the functional loss of the partially nephrectomized kidney after robot-assisted partial nephrectomy. CONCLUSIONS: Robot-assisted partial nephrectomy for completely endophytic renal tumors offers a shorter warm ischemia time and comparable positive surgical margin rate compared with conventional laparoscopic partial nephrectomy.

Preoperative risk stratification models after radical cystectomy for bladder cancer: A multi-center study.

OBJECTIVE: We investigated preoperative patient factors associated with prognosis in 263 bladder cancer (BC) patients undergoing radical cystectomy (RC). We also developed new risk stratification models for prognosis. METHODS: This retrospective study included patients treated at Tottori University Hospital and affiliated hospitals between January 2010 and December 2019. The relationship between preoperative patient factors and overall recurrence-free and cancer-specific survival (CSS) was analyzed. The modified Glasgow prognosis score (mGPS) was calculated using serum albumin and C-reactive protein (CRP) levels. Statistical analyses included the log-rank test and Cox proportional hazards regression. RESULTS: Eastern Cooperative Oncology Group performance status (ECOG-PS), mGPS, and clinical tumor stage independently predicted CSS in multivariate analysis. A new risk stratification model included ECOG-PS ≥2, clinical tumor stage ≥3, serum albumin <3.5 g/dL, and serum CRP >0.5 mg/dL. Risk groups were defined as 0 factors (low risk), 1-2 factors (intermediate risk), and 3-4 factors (high risk). High-risk patients showed significantly poorer 3-year cancer-free survival: 86.9% (low risk), 76.7% (intermediate risk), and 50.0% (high risk). CONCLUSIONS: ECOG-PS, clinical tumor stage, and mGPS are predictive of poor cancer-free survival post-RC for BC. Our model offers the potential for prognostic prediction in these patients.

Initial Experience and Surgical Setup of Robot-Assisted Nephroureterectomy Using the Hugo Robot-Assisted Surgery System.

Introduction and Hypothesis: Robot-assisted radical nephroureterectomy (RANU) has emerged as a valid alternative to open or laparoscopic nephroureterectomy in recent years. However, different types of robotic platforms can limit surgical maneuvers in various ways. This study aimed to describe the surgical procedure and demonstrate RANU's technical feasibility and safety using the Hugo robot-assisted surgery (RAS) system. Materials and Methods: Using the Hugo RAS system, we reported data from the first five consecutive patients who underwent RANU at Tottori University Hospital. We adjusted the docking angles of the four independent arm carts in each case and performed a complete RANU via a transperitoneal approach. We collected patients' sociodemographic and perioperative data, including complications, and compared them retrospectively with data obtained using the da Vinci surgical system. Results: Arms positions were modified after the first patient to be placed all at the back of the patient. Median overall operative time was 283 minutes (203-377) and the median time using the robotic system was 187 minutes (121-277). The median estimated blood loss was 20 mL (5-155). None of the patients required a blood transfusion and none suffered postoperative complications of Clavien-Dindo grade ≥3. These outcomes were similar to those obtained with the da Vinci Xi system. Conclusion: This series represents the first report of RANU executed using the novel Hugo RAS system. Our proposed arm-setup will assist other surgeons and help ensure safe implementation of RANU on the Hugo platform.

Effects of perirenal fat thickness on postoperative renal dysfunction in patients who underwent robot-assisted partial nephrectomy for renal tumours.

BACKGROUND: Despite partial nephrectomy (PN) renal function preservation benefits, postoperative renal dysfunction may occur. Perirenal fat thickness (PFT) is associated with renal dysfunction such as diabetes; however, its role in renal tumour surgery is unclear. This study investigates the role of PFT in renal function after robot-assisted partial nephrectomy (RAPN). METHODS: Pre-operative factors for postoperative renal dysfunction were analysed in 156 patients undergoing RAPN with ≥1-year follow-up. PFT measured using computed tomography categorised patients with PFT >21.0 mm (median) as high-PFT. RESULTS: Tumour size, total R.E.N.A.L. nephrometry score and its N component, renal calyx opening, achievement of trifecta, and PFT were risk factors for renal dysfunction 1 year postoperatively. Age ≥75 years (p = 0.024), total RNS ≥7 (p = 0.036), and PFT >21.0 mm (p = 0.002) significantly correlated with postoperative renal dysfunction. CONCLUSIONS: CT-measured PFT is a valuable predictor of postoperative renal dysfunction.

Japanese clinical practice guidelines for prostate cancer 2023.

This fourth edition of the Japanese Clinical Practice Guidelines for Prostate Cancer 2023 is compiled. It was revised under the leadership of the Japanese Urological Association, with members selected from multiple academic societies and related organizations (Japan Radiological Society, Japanese Society for Radiation Oncology, the Department of EBM and guidelines, Japan Council for Quality Health Care (Minds), Japanese Society of Pathology, and the patient group (NPO Prostate Cancer Patients Association)), in accordance with the Minds Manual for Guideline Development (2020 ver. 3.0). The most important feature of this revision is the adoption of systematic reviews (SRs) in determining recommendations for 14 clinical questions (CQs). Qualitative SRs for these questions were conducted, and the final recommendations were made based on the results through the votes of 24 members of the guideline development group. Five algorithms based on these results were also created. Contents not covered by the SRs, which are considered textbook material, have been described in the general statement. In the general statement, a literature search for 14 areas was conducted; then, based on the general statement and CQs of the Japanese Clinical Practice Guidelines for Prostate Cancer 2016, the findings revealed after the 2016 guidelines were mainly described. This article provides an overview of these guidelines.

Robotic versus open and laparoscopic pelvic exenterations for pelvic cancer: a multicenter propensity-matched analysis in Japan.

BACKGROUND: Pelvic exenteration (PE) is the last resort for achieving a complete cure for pelvic cancer; however, it is burdensome for patients. Minimally invasive surgeries, including robot-assisted surgery, have been widely used to treat malignant tumors and have also recently been used in PE. This study aimed to evaluate the safety and efficacy of robot-assisted PE (RPE) by comparing the outcomes of open PE (OPE) with those of conventional laparoscopic PE (LPE) for treating pelvic tumors. METHODS: Following the ethics committee approval, a multicenter retrospective analysis of patients who underwent pelvic exenteration between January 2012 and October 2022 was conducted. Data on patient demographics, tumor characteristics, and perioperative outcomes were collected. A 1:1 propensity score-matched analysis was performed to minimize group selection bias. RESULTS: In total, 261 patients met the study criteria, of whom 61 underwent RPE, 90 underwent OPE, and 110 underwent LPE. After propensity score matching, 50 pairs were created for RPE and OPE and 59 for RPE and LPE. RPE was associated with significantly less blood loss (RPE vs. OPE: 408 mL vs. 2385 ml, p < 0.001), lower transfusion rate (RPE vs. OPE: 32% vs. 82%, p < 0.001), and lower rate of complications over Clavien-Dindo grade II (RPE vs. OPE: 48% vs. 74%, p = 0.013; RPE vs. LPE: 48% vs. 76%, p = 0.002). CONCLUSION: This multicenter study suggests that RPE reduces blood loss and transfusion compared with OPE and has a lower rate of complications compared with OPE and LPE in patients with locally advanced and recurrent pelvic tumors.

Assessment of the accuracy of biparametric MRI/TRUS fusion-guided biopsy for index tumor evaluation using postoperative pathology specimens.

BACKGROUND: Multiparametric MRI (mpMRI) is widely used for the diagnosis, surveillance, and staging of prostate cancer. However, it has several limitations, including higher costs, longer examination times, and the use of gadolinium-based contrast agents. This study aimed to investigate the accuracy of preoperatively assessed index tumors (ITs) using biparametric MRI (bpMRI)/transrectal ultrasound (TRUS) fusion biopsy compared with radical prostatectomy (RP) specimens. METHODS: We included 113 patients diagnosed with prostate cancer through bpMRI/TRUS fusion-guided biopsies of lesions with a Prostate Imaging Reporting and Data System (PI-RADS) category ≥ 3. These patients underwent robot-assisted laparoscopic radical prostatectomy (RARP) at our institution between July 2017 and March 2023. We examined the localization of preoperative and postoperative ITs, the highest Gleason score (GS), and tumor diameter in these patients. RESULTS: The preoperative cT stage matched the postoperative pT stage in 53 cases (47%), while 31 cases (27%) were upstaged, and 29 cases (26%) were downstaged (Weighted Kappa = 0.21). The preoperative and postoperative IT localizations were consistent in 97 cases (86%). The concordance rate between Gleason groups in targeted biopsies and RP specimens was 51%, with an upgrade in 25 cases (23%) and a downgrade in 27 cases (25%) (Weighted Kappa = 0.42). The maximum diameter of the IT and the maximum cancer core length on biopsy were correlated with the RP tumor's maximum diameter (p < 0.001 for both). CONCLUSION: The diagnostic accuracy of bpMRI/TRUS fusion biopsy is comparable to mpMRI, suggesting that it can be a cost-effective and time-saving alternative.

Standardization of robot-assisted pelvic lymph node dissection-Development of a common understanding of regional anatomy and surgical technique based on cross-disciplinary discussion among colorectal surgery, urology, and gynecology.

BACKGROUND: Pelvic lymph node dissection is a procedure performed in gastroenterological surgery, urology, and gynecology. However, due to discrepancies in the understanding of pelvic anatomy among these departments, cross-disciplinary discussions have not been easy. Recently, with the rapid spread of robotic surgery, the importance of visual information in understanding pelvic anatomy has become even more significant. In this project, we attempted to clarify a shared understanding of pelvic anatomy through cross-disciplinary discussions. METHOD: From May 2020 to November 2021, a total of 11 discussions were held entirely online with 5 colorectal surgery specialists, 4 urologists, and 4 gynecologists. The discussions focused on evidence from each specialty and surgical videos, aiming to create a universally understandable pelvic anatomical illustration. RESULTS: The common area of dissection recognized across the three departments was identified as the obturator lymph nodes. A dynamic illustration of pelvic anatomy was created. In addition to a bird's-eye view of the pelvis, a pelvic half view was developed to enhance understanding of the deeper pelvic anatomy. The following insights were incorporated into the illustration: (1) the cardinal ligament in gynecology partly overlaps with the vesicohypogastric fascia in colorectal surgery; (2) the obturator lymph nodes continue cephalad into the fossa of Marcille in urology; and (3) the deep uterine vein in gynecology corresponds to the inferior vesical vein in colorectal surgery. CONCLUSION: Based on the dynamic illustration of pelvic anatomy from cross-disciplinary discussions, we anticipate advancements in pelvic lymph node dissection aiming for curative and safe outcomes.

Supervised Pelvic Floor Muscle Training Improves Sexual Function and Diminishes Sexual Distress in Women with Relapsing-Remitting Multiple Sclerosis: A Randomised Controlled Study.

This study investigates the impact of pelvic floor muscle training (PFMT) on sexual function and distress in women with multiple sclerosis (MS), a prevalent chronic nervous system disorder associated with sexual dysfunction. This study's primary aim was to assess the effectiveness of PFMT at improving sexual function and alleviating sexual distress in this population. In a randomised controlled trial, 82 women with MS were divided into two groups: Group A (41 women) underwent 12 weeks of PFMT, while Group B (41 women) served as a control group with no intervention. Both groups were assessed at the beginning and end of this study using the Female Sexual Function Index (FSFI) and Female Sexual Distress Scale-Revised (FSDS-R). Statistical analysis, including Chi-square tests, was employed to compare the outcomes between the two groups, with a p-value of less than 0.05 considered significant. The results revealed no significant differences in baseline sexual function and distress between the groups. However, at the conclusion of the 12-week period, Group A exhibited statistically significant improvements in nearly all domains of FSFI and FSDS-R compared to Group B, except in the pain domain. This study concludes that PFMT can effectively enhance sexual function and reduce sexual distress in women suffering from MS. These findings underscore the potential of PFMT as a therapeutic intervention in managing sexual dysfunction associated with MS.

Summary of the Clinical Practice Guidelines for Upper Tract Urothelial Carcinoma 2023 by the Japanese Urological Association.

This article is an English translation of the Clinical Practice Guidelines for Upper Tract Urothelial Carcinoma (2nd edition) published in June 2023. The Japanese Urological Association's (JUA) Guidelines Committee on Upper Tract Urothelial Carcinoma (UTUC) created a 2023 update guideline to support clinicians' current evidence-based management of UTUC and to incorporate its recommendations into clinical practice. The new guideline adhered as closely as possible to the Minds Manual for Guideline Development 2020 ver. 3.0. Findings related to epidemiological, pathological, diagnosis, treatment, and follow-up were reviewed. In addition, seven clinical questions (CQs) were set to determine the grade of recommendation and level of evidence. Preconceptions and biases were removed from the preparation process, the overall evidence was evaluated appropriately, and recommendations were made after fully considering the balance between benefits and harms. Although the evidence is still insufficient to be taken up as a CQ, the latest important information is described in seven columns, and clinical issues that should be resolved in the future related to the CQ are described as recommendations for tomorrow. We hope that these guidelines will help medical professionals, patients, and their families involved in the treatment of UTUC in their decision-making, and hope that a critical review of these guidelines will lead to further refinements in the next edition.