Prognostic Importance of Lymphovascular Invasion for Specific Subgroup of Patients with Prostate Cancer After Robot-Assisted Radical Prostatectomy (The MSUG94 Group).

OBJECTIVE: This study aimed to investigate whether lymphovascular invasion (LVI) was associated with oncological outcomes in patients with prostate cancer (PCa) undergoing robotic-assisted radical prostatectomy (RARP). METHODS: This retrospective multicenter cohort study was conducted on 3195 patients with PCa who underwent RARP in nine institutions in Japan. The primary endpoints were the associations between biochemical recurrence (BCR) and LVI and between BCR and clinicopathological covariates, while the secondary endpoints were the association between LVI and the site of clinical recurrence and metastasis-free survival (MFS). RESULTS: In total, 2608 patients met the inclusion criteria. At the end of the follow-up period, 311 patients (11.9%) were diagnosed with BCR and none died of PCa. In patients with pathological stage T2 (pT2) + negative resection margins (RM-), and pT3+ positive RM (RM+), LVI significantly worsened BCR-free survival (BRFS). For patients with PCa who had pT3 and RM+, the 2-year BRFS rate in those with LVI was significantly worse than in those without LVI. Patients with LVI had significantly worse MFS than those without LVI with respect to pT3, RM+, and pathological Gleason grade (pGG). In multivariate analysis, LVI was significantly associated with BRFS in patients with pT3 PCa, and with worse MFS in PCa patients with pT3, RM+, and pGG ≥ 4. CONCLUSIONS: LVI was an independent prognostic factor for recurrence and metastasis after RARP, particularly in patients with pT3 and RM+ PCa. Locally advanced PCa with positive LVI and RM+ requires careful follow-up because of the high likelihood of recurrence.

Prognostic factors among patients with pathological Grade Group 5 prostate cancer based on robot-associated radical prostatectomy specimens from a large Japanese cohort (MSUG94).

PURPOSE: There are no definitive prognostic factors for patients with pathological Grade Group 5 (pGG 5) prostate cancer (PCa) undergoing robot-associated radical prostatectomy (RARP). This study aimed to explore the prognostic factors among patients with pGG 5 PCa in a large Japanese cohort (MSUG94). METHODS: This retrospective, multi-institutional cohort study was conducted between 2012 and 2021 at ten centers in Japan and included 3195 patients. Patients with clinically metastatic PCa (cN1 or cM1) and those receiving neoadjuvant and/or adjuvant therapy were excluded. Finally, 217 patients with pGG5 PCa were analyzed. RESULTS: The median follow-up period was 28.0 months. The 3- and 5-year biochemical recurrence-free survival (BCRFS) rates of the overall population were 66.1% and 57.7%, respectively. The optimal threshold value (47.2%) for the percentage of positive cancer cores (PPCC) with any GG by systematic biopsy was chosen based on receiver operating characteristic curve analysis. Univariate analysis revealed that the prostate-specific antigen level at diagnosis, pT, pN, positive surgical margins (PSMs), lymphovascular invasion, and PPCC were independent prognostic factors for BCRFS. A multivariate analysis revealed that PSMs and PPCC were independent prognostic factors for BCRFS. Using these two predictors, we stratified BCRFS, metastasis-free survival (MFS), and castration-resistant PCa-free survival (CRPC-FS) among patients with pGG 5 PCa. CONCLUSION: The combination of PSMs and PPCC may be an important predictor of BCRFS, MFS, and CRPC-FS in patients with pGG 5 PCa undergoing RARP.

Nomogram Predicting Locally Advanced Prostate Cancer in Patients with Clinically Organ-Confined Disease Who Underwent Robot-Assisted Radical Prostatectomy: A Retrospective Multicenter Cohort Study in Japan (The MSUG94 Group).

PURPOSE: We created a clinically applicable nomogram to predict locally advanced prostate cancer using preoperative parameters and performed external validation using an external independent validation cohort. PATIENTS AND METHODS: From a retrospective multicenter cohort study of 3622 Japanese patients with prostate cancer who underwent robot-assisted radical prostatectomy at ten institutions, the patients were divided into two groups (MSUG cohort and validation cohort). Locally advanced prostate cancer was defined as pathological T stage ≥ 3a. A multivariable logistic regression model was used to identify factors strongly associated with locally advanced prostate cancer. Bootstrap area under the curve was calculated to assess the internal validity of the prediction model. A nomogram was created as a practical application of the prediction model, and a web application was released to predict the probability of locally advanced prostate cancer. RESULTS: A total of 2530 and 427 patients in the MSUG and validation cohorts, respectively, met the criteria for this study. On multivariable analysis, initial prostate-specific antigen, prostate volume, number of cancer-positive and cancer-negative biopsy cores, biopsy grade group, and clinical T stage were independent predictors of locally advanced prostate cancer. The nomogram predicting locally advanced prostate cancer was demonstrated (area under the curve 0.72). Using a nomogram cutoff of 0.26, 464 of 1162 patients (39.9%) could be correctly diagnosed with pT3, and 2311 of 2524 patients (91.6%) could avoid underdiagnosis. CONCLUSIONS: We developed a clinically applicable nomogram with external validation to predict the probability of locally advanced prostate cancer in patients undergoing robot-assisted radical prostatectomy.

Impact of diagnostic ureteral catheterization on intravesical tumour recurrence following radical nephroureterectomy for upper tract urothelial carcinoma.

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.

Novel utility of Vesical Imaging-Reporting and Data System in multimodal treatment for muscle-invasive bladder cancer.

OBJECTIVES: To examine the clinical significance of the Vesical Imaging-Reporting and Data System (VI-RADS) in predicting outcome of multimodal treatment (MMT) in muscle-invasive bladder cancer (MIBC) patients. METHODS: We reviewed 78 pathologically proven MIBC patients who underwent MMT including transurethral resection and chemoradiotherapy, followed by partial or radical cystectomy. Treatment response was assessed through histologic evaluation of cystectomy specimens. Two radiologists categorized the index lesions of pretherapeutic MRI according to the 5-point VI-RADS score. The associations of VI-RADS score with the therapeutic effect of MMT were analyzed. The diagnostic performance of VI-RADS scores with a cut-off VI-RADS scores ≤ 2 or ≤ 3 for predicting pathologic complete response to MMT (MMT-CR) was evaluated. RESULTS: MMT-CR was achieved in 2 (100%) of VI-RADS score 1 (n = 2), 16 (84%) of score 2 (n = 19), 12 (86%) of score 3 (n = 14), 7 (64%) of score 4 (n = 11), and 14 (44%) of score 5 (n = 32). VI-RADS score was inversely associated with the incidence of MMT-CR (p = 0.00049). The cut-off VI-RADS score ≤ 2 and ≤ 3 could predict the favorable therapeutic outcome of MMT with high specificity (0.89 with 95% confidence interval [CI]: 0.71-0.98 and 0.82 with 95% CI: 0.62-0.94, respectively) and high positive predictive value (0.86 with 95% CI: 0.64-0.97 and 0.86 with 95% CI: 0.70-0.95, respectively). CONCLUSION: VI-RADS score may serve as an imaging marker in MIBC patients for predicting the therapeutic outcome of MMT. CLINICAL RELEVANCE STATEMENT: Muscle-invasive bladder cancer patients with a lower Vesical Imaging-Reporting and Data System score can be a good candidate for bladder-sparing treatment incorporating multimodal treatment. KEY POINTS: • Vesical Imaging-Reporting and Data System (VI-RADS) score was potentially valuable for classifying pathologic tumor response in patients with muscle-invasive bladder cancer. • The likelihood of achieving complete response of multimodal treatment (MMT) decreased with increasing VI-RADS score. • VI-RADS score could serve as an imaging marker that optimizes patient selection for MMT.

Prognostic differences among the positive surgical margin locations following robot-assisted radical prostatectomy in a large Japanese cohort (the MSUG94 group).

BACKGROUND: To investigate whether subgroups of prostate cancer patients, stratified by positive surgical margin locations, have different oncological outcomes following robot-assisted radical prostatectomy. METHODS: A retrospective multicenter cohort study in prostate cancer patients undergoing robot-assisted radical prostatectomy was conducted at 10 institutions in Japan. Pre- and post-operative outcomes were collected from enrolled patients. Biochemical recurrence and clinical and pathological variables were evaluated among subgroups with different positive surgical margin locations. RESULTS: A total of 3195 patients enrolled in this study. Data from 2667 patients (70.1% [N = 1869] with negative surgical margins and 29.9% [N = 798] with positive surgical margins based on robot-assisted radical prostatectomy specimens) were analyzed. The median follow-up period was 25.0 months. The numbers of patients with apex-only, middle-only, bladder-neck-only, seminal-vesicle-only and multifocal positive surgical margins were 401, 175, 159, 31 and 32, respectively. In the multivariate analysis, PSA level at surgery, pathological Gleason score based on robot-assisted radical prostatectomy specimens, pathological T stage, pathological N stage and surgical margin status were independent risk factors significantly associated with biochemical recurrence-free survival. Patients undergoing robot-assisted radical prostatectomy with multifocal positive surgical margins and seminal-vesicle-only positive surgical margins were associated with worse biochemical recurrence-free survival than those with apex-only, middle-only and bladder-neck-only positive surgical margins. Patients undergoing robot-assisted radical prostatectomy with apex-only positive surgical margins, the most frequent positive surgical margin location, were associated with more favorable biochemical recurrence-free survival that those with middle-only and bladder-neck-only positive surgical margins. The study limitations included the lack of central pathological specimen evaluation. CONCLUSIONS: Although positive surgical margin at any locations is a biochemical recurrence risk factor after robot-assisted radical prostatectomy, positive surgical margin location status should be considered to accurately stratify the biochemical recurrence risk after robot-assisted radical prostatectomy.

Association of hospital volume with perioperative and oncological outcomes of robot-assisted laparoscopic radical prostatectomy: a retrospective multicenter cohort study.

BACKGROUND: This retrospective multicenter cohort study investigated the association of hospital volume with perioperative and oncological outcomes in patients treated with robot-assisted radical prostatectomy (RARP). METHODS: We collected the clinical data of patients who underwent RARP at eight institutions in Japan between September 2012 and August 2021. The patients were divided into two groups based on the treatment site-high- and non-high-volume hospitals. We defined a high-volume hospital as one where RARP was performed for more than 100 cases per year. RESULTS: After excluding patients who received neoadjuvant therapy, a total of 2753 patients were included in this study. In the high-volume hospital group, console time and estimated blood loss were significantly (p < 0.001) lower than that of the non-high-volume hospital group. However, the continence rate at 3 months after RARP, positive surgical margins, and prostate-specific antigen (PSA)-relapse-free survival showed no significant differences between the two groups. Furthermore, the console time was significantly shorter after 100 cases in the non-high-volume hospital group but not in the high-volume hospital group. CONCLUSIONS: A higher hospital volume was significantly associated with shorter console time and less estimated blood loss. However, oncological outcomes and early continence recovery appear to be comparable regardless of the hospital volume in Japan.

A phase II randomized trial of metastasis-directed therapy with alpha emitter radium-223 in men with oligometastatic castration-resistant prostate cancer (MEDAL).

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.

Superior detection of significant prostate cancer by transperineal prostate biopsy using MRI-transrectal ultrasound fusion image guidance over cognitive registration.

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.

Preoperative models incorporating the systemic immune-inflammation index for predicting prognosis and muscle invasion in patients with non-metastatic upper tract urothelial carcinoma.

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. RESULTS: During 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.

The Impact of Gleason Grade 3 as a Predictive Factor for Biochemical Recurrence after Robot-Assisted Radical Prostatectomy: A Retrospective Multicenter Cohort Study in Japan (The MSUG94 Group).

Background and Objectives: This study's objective was to examine patients treated with robot-assisted radical prostatectomy (RARP) for intermediate-risk prostate cancer (IR-PCa), and to identify preoperative risk factors for biochemical recurrence (BCR) in these patients in Japan. Materials and Methods: We conducted a retrospective multicenter cohort study of patients with PCa who underwent RARP at 10 institutions in Japan. A total of 3195 patients were enrolled in this study. We focused on patients with IR-PCa who underwent RARP. We obtained data on pre- and postoperative covariates from the enrolled patients. Biochemical recurrence-free survival was the primary endpoint of this study. We also identified useful preoperative predictive factors for BCR in patients with IR-PCa after RARP. Results: A total of 1144 patients with IR-PCa were enrolled in this study. The median follow-up period was 23.7 months. At the end of the follow-up period, 94 (8.2%) patients developed BCR. The 2 and 3 year biochemical recurrence-free survival (BRFS) rates were 92.2% and 90.2%, respectively. Using the Kaplan-Meier method, Gleason grade (GG) 3 was significantly associated with poor BRFS compared with ≤GG 2. In multivariate analysis, GG 3 was a significant predictive factor for BCR in patients with IR-PCa. Conclusions: The results of the study indicated a significant relationship between GG 3 and post-RARP BCR in patients with IR-PCa.

Prognostic significance of the controlling nutritional status score in patients with metastatic renal cell carcinoma diagnosed before an era of first-line immune-oncology combination therapies.

OBJECTIVE: To explore the prognostic role of the controlling nutritional status score in patients with metastatic renal cell carcinoma. METHODS: We retrospectively analyzed 107 patients with metastatic renal cell carcinoma who received their diagnosis between 2007 and 2018 and were treated with or without a first-line interferon or tyrosine kinase inhibitor at a single cancer center. The controlling nutritional status score was based on values for albumin, lymphocyte count and total cholesterol at the metastatic renal cell carcinoma diagnosis. Association of the controlling nutritional status score and clinical variables, including the Memorial Sloan-Kettering Cancer Center and the International Metastatic Renal Cell Carcinoma Database Consortium risk classifications, with overall survival was examined using the Cox proportional hazard model. Predictive accuracy of the prognostic factors was assessed using Harrell's concordance index. RESULTS: First-line interferon and tyrosine kinase inhibitor were given to 48 (45%) and 41 (38%) patients, respectively, and 28 (26%) and 33 (31%) patients underwent cytoreductive nephrectomy and metastasectomy, respectively. During follow-up (median: 36.3 months), 64 patients died. The median controlling nutritional status score was 2 (range: 0-8). A controlling nutritional status score ≥ 2 was significantly associated with shorter overall survival (P < 0.01) independently of the Memorial Sloan-Kettering Cancer Center and International Metastatic Renal Cell Carcinoma Database Consortium risk classifications. Integration of the controlling nutritional status score into the Memorial Sloan-Kettering Cancer Center and International Metastatic Renal Cell Carcinoma Database Consortium risk classifications improved concordance index from 0.702 to 0.770 and from 0.698 to 0.749, respectively. CONCLUSION: The controlling nutritional status score may serve as a prognostic biomarker objectively reflecting the general physical condition of patients with metastatic renal cell carcinoma treated with or without first-line interferon or tyrosine kinase inhibitor in terms of nutritional and immuno-inflammatory status.

Who Can Avoid Biopsy of Magnetic Resonance Imaging-Negative Lobes without Compromising Significant Cancer Detection among Men with Unilateral Magnetic Resonance Imaging-Positive Lobes?

OBJECTIVES: To assess whether biopsy of multiparametric magnetic resonance imaging (MRI)-negative lobes can be avoided without compromising significant cancer (SC) detection among men with unilateral MRI-positive lobes. METHODS: From April 2013 to April 2019, 322 men with elevated prostate-specific antigen (PSA <20 ng/mL) and unilateral MRI-positive lobes underwent targeted 4-core and systematic 14-core biopsy. MRI findings were prospectively collected and evaluated according to the Prostate Imaging-Reporting and Data System (PI-RADS) version 2, and scores ≥3 were considered positive. SC was defined as Gleason score ≥3 + 4 or maximal cancer length ≥5 mm. We developed predictive models of overall cancer and SC in MRI-negative lobes and evaluated the performance of these models. RESULTS: Detection rates of overall cancer/SC were 69%/61% for the overall cohort, 58%/48% for MRI-positive lobes, and 36%/20% for MRI-negative lobes. Age ≥75 years, PSA density ≥0.3, and PI-RADS ≥4 were independently predictive of both overall cancer and SC in MRI-negative lobes; 1 point was assigned for each risk factor, and the predictive score was defined as the sum of points (0-3) for both overall cancer and SC. Areas under the curve of the model for overall cancer/SC were 0.67/0.71. In the decision curve analysis, the model was of value above the threshold probability of 13%/6% for detecting overall cancer/SC in MRI-negative lobes. Of 40 men with score 0, overall cancer/SC was detected in the MRI-negative lobe in 4 (10%)/1 (2.5%). CONCLUSION: Biopsies of MRI-negative lobes may be avoided without compromising SC detection using our predictive model.

[Clinical Significance of Total Pancreatectomy for Multiple Pancreatic Metastases from Renal Cancer].

With the progress of replacement therapy for pancreatic endocrine and exocrine functions, the indications for a total pancreatectomy are expanding, and reports of multiple pancreatic metastases of renal cancer are on the rise. In the present, we investigated the utility of a total pancreatectomy for multiple pancreatic metastases of renal cancer. The subjects were 8 patients who underwent a total pancreatectomy for multiple pancreatic metastases of renal cancer between 2012 and 2021. The median, postoperative observation period was 31(3-92)months. Six of 8 patients survived without cancer, and one survived with chemotherapy(pazopanib plus axitinib)plus radiation therapy(maintaining stable disease). The one, remaining patient died of hypoglycemia. Of the 8 patients, 4 survived for 2 years or more, and 2 survived for more than 5 years. Postoperative, support for endocrine and exocrine functions is indispensable, but a total pancreatectomy for multiple pancreatic metastases of renal cancer promises to be a viable treatment option owing to its favorable long-term prognosis.

Prognostic Significance of the Controlling Nutritional Status (CONUT) Score in Patients with Advanced Renal Cell Carcinoma Treated with Nivolumab after Failure of Prior Tyrosine Kinase Inhibitors.

PURPOSE: The controlling nutritional status (CONUT) score, consisting of albumin, lymphocytes and total cholesterol, is a validated, objective tool for nutritional assessment. Patients with advanced cancer frequently have malnutrition in association with cachexia and chronic inflammation. We explored the prognostic significance of the CONUT score in patients with advanced renal cell carcinoma receiving nivolumab. MATERIALS AND METHODS: This retrospective study included 60 patients with stage IV renal cell carcinoma treated with nivolumab after failure of prior tyrosine kinase inhibitors at 2 cancer centers between 2016 and 2019. Associations of the CONUT score with progression-free survival, cancer specific survival and tumor shrinkage rate were assessed. RESULTS: The median (range) CONUT score was 2 (0-10). During followup periods 29 and 14 patients exhibited disease progression and died of cancer, respectively. Both progression-free survival and cancer specific survival were significantly stratified by CONUT scores of 0 to 1, 2 to 4 and 5 or more (p=0.002). A CONUT score of 5 or more (versus score 0 to 1) was independently associated with unfavorable progression-free survival (HR 5.18, p=0.003) and cancer specific survival (HR 15.34, p=0.014), as was the absence of prior nephrectomy (HR 4.23, p=0.004 and HR 6.57, p=0.001, respectively). C-indices of the CONUT score for predicting progression-free survival and cancer specific survival were 0.694 and 0.737, respectively. The CONUT score was significantly associated with the best response to nivolumab with the median tumor shrinkage rate of -23%, +8% and +24% for CONUT scores of 0 to 1, 2 to 4 and 5 or more, respectively (p=0.021). CONCLUSIONS: The CONUT score may be useful to predict the clinical outcomes and therapeutic response in patients with advanced renal cell carcinoma receiving nivolumab.

Contact with renal sinus is associated with poor prognosis in surgically treated pT1 clear cell renal cell carcinoma.

OBJECTIVE: To investigate the prognostic significance of contact with the renal sinus in patients with clear cell renal cell carcinoma. METHODS: A total of 787 pT1N0M0 clear cell renal cell carcinoma patients who had undergone radical or partial nephrectomy were reviewed retrospectively. A tumor in contact with the renal sinus was defined as a tumor radiologically attached to the renal sinus. Metastatic-free survival rates were analyzed in the total and propensity score-matched cohorts. A risk score model for metastasis after surgery was developed. RESULTS: Of the 787 patients, 411 (52.2%) had tumors in contact with renal sinus. The contact with renal sinus group showed poorer metastatic-free survival in both total and matched cohorts. In multivariate analysis, contact with renal sinus was an independent prognostic factor of metastasis, as well as Fuhrman grade, microvascular invasion and age. The scoring model likewise consisted of Fuhrman grade, microvascular invasion, age and contact with renal sinus. Metastasis-free survival curves were clearly stratified according to risk, with 5-year metastasis-free survival rates of 95.7% and 65.2% in the low- and high-risk groups, respectively (P < 0.001). CONCLUSIONS: Contact with the renal sinus is a significant risk factor for metastasis in T1 clear cell renal cell carcinoma after surgery. More intensive follow up should be recommended for patients with renal cell carcinoma that is in contact with the renal sinus.

Selective tetramodal bladder-preservation therapy, incorporating induction chemoradiotherapy and consolidative partial cystectomy with pelvic lymph node dissection for muscle-invasive bladder cancer: oncological and functional outcomes of 107 patients.

OBJECTIVES: To evaluate the oncological and functional outcomes associated with selective tetramodal bladder-sparing therapy, comprising maximal transurethral resection of bladder tumour (TURBT), induction chemoradiotherapy (CRT), and consolidative partial cystectomy (PC) with pelvic lymph node dissection (PLND). MATERIALS AND METHODS: In the present study, 154 patients with non-metastatic muscle-invasive bladder cancer (MIBC), prospectively enrolled in the tetramodal bladder-preservation protocol, were analysed. After TURBT and induction CRT, patients showing complete remission were offered consolidative PC with PLND for the achievement of bladder preservation. Pathological response to induction CRT was evaluated using PC specimens. Oncological and functional outcomes after bladder preservation were evaluated using the following endpoints: MIBC-recurrence-free survival (RFS); cancer-specific survival (CSS); overall survival (OS), and cross-sectional assessments of preserved bladder function and quality of life (QoL) including uroflowmetry, bladder diary, International Prostate Symptom Score, Overactive Bladder Symptom Score and the 36-item Short-Form Health Survey (SF-36) score. RESULTS: The median follow-up period was 48 months. Complete MIBC remission was achieved in 121 patients (79%) after CRT, and 107 patients (69%) completed the tetramodal bladder-preservation protocol comprising consolidative PC with PLND. Pathological examination in these 107 patients revealed residual invasive cancer (≥pT1) that was surgically removed in 11 patients (10%) and lymph node metastases in two patients (2%). The 5-year MIBC-RFS, CSS and OS rates in the 107 patients who completed the protocol were 97%, 93% and 91%, respectively. As for preserved bladder function, the median maximum voided volume, post-void residual urine volume, and nighttime frequency were 350 mL, 25 mL, and two voids, respectively. In the SF-36, patients had favourable scores, equivalent to the age-matched references in all the QoL scales. CONCLUSION: Selective tetramodal bladder-preservation therapy, incorporating consolidative PC with PLND, yielded favourable oncological and functional outcomes in patients with MIBC. Consolidative PC may have contributed to the low rate of MIBC recurrence in patients treated according to this protocol.

Impact of fluorodeoxyglucose uptake on positron emission tomography/computed tomography on chemosensitivity and survival in patients with metastatic urothelial carcinoma.

OBJECTIVES: To evaluate the impact of fluorodeoxyglucose uptake on positron emission tomography/computed tomography on chemosensitivity and survival in patients with metastatic urothelial carcinoma. METHODS: The present study assessed 51 metastatic urothelial carcinoma patients undergoing fluorodeoxyglucose positron emission tomography/computed tomography before first-line systemic chemotherapy. Fluorodeoxyglucose uptake in metastases was evaluated using the maximum standardized uptake value, which was measured for all eligible lesions, and the highest value among the maximum standardized uptake value measurements in each case was defined as the highest maximum standardized uptake value. The associations between the highest maximum standardized uptake value and objective response rate to chemotherapy, progression-free survival or cancer-specific survival were analyzed. For cancer-specific survival, the C-index was compared between multivariate models that incorporated predictors in the Bajorin model including the Karnofsky performance status and the presence of visceral metastasis, and the Apolo model additionally including hemoglobin and albumin levels, with/without the highest maximum standardized uptake value. RESULTS: The median age was 69 years. The Karnofsky performance status was ≥80% for all patients. Visceral metastasis was observed in 12 patients (24%). The objective response rate, median progression-free survival and median cancer-specific survival were 61%, 9 and 26 months in the entire cohort, respectively. The higher highest maximum standardized uptake value was significantly associated with a lower objective response rate, shorter progression-free survival and shorter cancer-specific survival (P = 0.01, <0.001 and 0.004, respectively). On multivariate analyses, the highest maximum standardized uptake value was an independent predictor for all end-points. In the multivariate models for cancer-specific survival, the C-index improved from 0.559 to 0.601 and from 0.604 to 0.652 by adding the highest maximum standardized uptake value to the parameter set of the Bajorin model and Apolo model, respectively. CONCLUSIONS: Higher fluorodeoxyglucose uptake in metastases was significantly and independently associated with poor chemosensitivity and worse survival outcomes. Fluorodeoxyglucose positron emission tomography/computed tomography might aid in patient counseling and treatment decisions for metastatic urothelial carcinoma patients.

Metabolic and Molecular Basis of Sarcopenia: Implications in the Management of Urothelial Carcinoma.

Sarcopenia, which represents the degenerative and systemic loss of skeletal muscle mass, is a multifactorial syndrome caused by various clinical conditions. Sarcopenia reflects not only frailty and poor general health status, but also the possible presence of advanced or progressive cancer or cancer cachexia. Therefore, sarcopenia affects the management of cancer-bearing patients, including those with urothelial carcinoma. Recently, growing evidence has shown that sarcopenia is significantly associated with higher rates of treatment-related complications and worse prognosis in patients with urothelial carcinoma, including muscle-invasive bladder cancer, upper tract urothelial carcinoma, and advanced urothelial carcinoma. Moreover, several studies reported that a post-therapeutic increase in skeletal muscle mass predicts favorable prognosis in urothelial carcinoma patients. To further explore the role of sarcopenia in the management of urothelial carcinoma patients, comprehensive understanding of its pathophysiology is vital. In this article, we reviewed the metabolic and molecular basis of cancer cachexia and sarcopenia. From this viewpoint, we discussed the possible mechanism of changes in skeletal muscle mass during the course of treatment.

[A Case of Bladder Urothelial Carcinoma with Hepatic Metastasis Achieving Histologically Complete Response by Multimodal Treatment Including Pembrolizumab].

A 70s man underwent transurethral resection of the bladder tumor(TURBT)at a previous hospital. The pathological diagnosis was urothelial carcinoma pT1. Nine months later, recurrence appeared in the bladder and he underwent repeated TURBT. The pathological diagnosis was also pT1 and he was administered 8 courses of intravesical BCG therapy. Fourteen months after the first operation, computed tomography scans showed new lesions in the liver. Therefore, he was referred to our hospital. Because biopsy from the hepatic lesion confirmed the diagnosis of metastatic urothelial carcinoma, he received 10 courses of gemcitabine plus cisplatin(GC)and radiofrequency ablation. However, daughter nodule and enlargement of the main tumor were revealed on MRI 33 months after the initial TURBT. After 5 courses of pembrolizumab that limited the potential for hepatic metastases, he had no evidence of other metastatic sites and underwent laparoscopic right hepatectomy. There was no viable carcinoma in the pathological specimens of the hepatic lesions. Six months after hepatectomy, the patient has a high quality of life without any recurrence.