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.

Prognostic significance of inflammatory markers in patients with advanced renal cell carcinoma receiving nivolumab plus ipilimumab.

BACKGROUND: A useful biomarker for the efficacy of immune checkpoint inhibitors (ICIs) in advanced renal cell carcinoma (RCC) has not yet been established. This study aims to investigate whether inflammatory markers are associated with the efficacy of nivolumab plus ipilimumab therapy before and during treatment. METHODS: Data from patients with advanced clear cell RCC who received a combination treatment of nivolumab plus ipilimumab were retrospectively analyzed. The neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and C-reactive protein (CRP) levels were assessed at baseline and 3, 6, and 9 weeks after treatment initiation. The correlation between these inflammatory markers and the patient's prognosis was investigated. RESULTS: Eighty-four patients were identified. The multivariate analysis identified NLR at week 3, CRP at week 6, and NLR and CRP at week 9 as the consistent predictor associated with poor overall survival (OS) at each time point. The survival analysis and receiver operating characteristic (ROC) curve analysis revealed that an NLR of ≥ 2.4 at week 3, CRP of ≥ 1.4 mg/dL at week 6, and NLR of ≥ 4.8 and CRP of ≥ 1.0 mg/dL at week 9 were associated with worse OS (hazard ratios (HR) = 5.70, P = 0.008, HR = 3.23, P = 0.004, HR = 7.38, P < 0.001 and HR = 3.55, P = 0.002). CONCLUSIONS: Both NLR and CRP were considered useful biomarkers for understanding the prognosis during nivolumab plus ipilimumab therapy. Furthermore, an NLR of ≥ 4.8 and CRP of ≥ 1.0 mg/dL at week 9 are helpful in reconsidering treatment continuation.

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 worsening surgically induced chronic kidney disease (CKD-S) in preoperative CKD-naïve patients on survival in renal cell carcinoma.

OBJECTIVES: To evaluate effects of worsening surgically induced chronic kidney disease (CKD-S) on oncological and non-oncological survival outcomes in renal cell carcinoma (RCC). PATIENTS AND METHODS: We performed a retrospective analysis of patients who underwent partial (PN) or radical nephrectomy (RN) and were free of preoperative CKD (estimated glomerular filtration rate [eGFR] ≥60 mL/min/1.73 m2 ). Patients were stratified by CKD stage at last follow-up: no CKD-S (eGFR ≥60 mL/min/1.73 m2 ), de novo CKD-S 3a (eGFR 45-59 mL/min/1.73 m2 ), CKD-S 3b (eGFR <45 and ≥30 mL/min/1.73 m2 ) and CKD-S 4 (eGFR <30 and ≥15 mL/min/1.73 m2 ). The primary outcome was all-cause mortality (ACM). Secondary outcomes included non-cancer mortality (NCM), cancer-specific mortality (CSM) and de novo CKD-S Stage 3/4. Multivariable analysis (MVA) was utilised to identify risk factors for outcomes. Kaplan-Meier analysis (KMA) was utilised to evaluate overall (OS), non-cancer (NCS), and cancer-specific survival with respect to CKD-S categories. RESULTS: We analysed 3239 patients. The mean preoperative and last-follow-up eGFRs were 87.4 and 69.5 mL/min/1.73 m2 , respectively. On last follow-up, 57.9% (n = 1876) had no CKD-S, 18.7% (n = 606) had CKD-S 3a, 15.1% (n = 489) had CKD-S 3b and 8.3% (n = 268) had CKD-S 4. On MVA, de novo CKD-S 3b and 4 were independently associated with ACM (hazard ratios [HRs] 1.3-2.1, P = 0.003-0.001) and NCM (HRs 1.5-2.8, P = 0.021-0.001), but not CSM (P = 0.219-0.909); de novo CKD-S 3a was not predictive for any mortality outcomes (P = 0.102-0.81). RN was independently associated with CKD-S 3-4 (HRs 1.78-1.99, P < 0.001-0.035). Comparing no CKD-S, CKD-S 3a, CKD-S 3b and CKD-S 4, KMA demonstrated worsening outcomes with progressive CKD-S stage: 5-year OS 84% vs 78% vs 71% vs 60% (P < 0.001) and 5-year NCS 93% vs 87% vs 83% vs 72% (P < 0.001). CONCLUSION: Development of CKD-S Stage 3b and 4, but not 3a, was associated with worsened ACM and NCM. The decision to proceed with nephron preservation via PN should be individualised based on oncological risk and risk of functional decline to CKD-S 3b or 4, and not CKD-S 3a.

The role of multimodal salvage therapy in the management of recurrent adrenocortical carcinoma.

BACKGROUND: Adrenocortical carcinoma is an aggressive tumor which often recurs despite apparent complete resection. This study assessed the long-term outcomes for patients with recurrent adrenocortical carcinoma after multimodal salvage therapy with chemotherapy, chemoradiotherapy and surgery. METHODS: We retrospectively reviewed medical records of patients who had a pathological diagnosis of adrenocortical carcinoma between 1996 and 2017. Kaplan-Meier curves were used to assess progression-free and cancer-specific survivals among all patients and cancer-specific survival among patients with tumor recurrence. Log-rank test was used to compare patient survivals by modality of salvage therapy (chemotherapy, chemoradiotherapy and chemotherapy/chemoradiotherapy plus surgery). RESULTS: Of 20 patients who underwent initial surgery, recurrence occurred in 14 (70%) with a median interval of 7.5 (range 1.0-12.6) months. Salvage therapy provided was chemotherapy only (n = 7), chemoradiotherapy (n = 2) and chemotherapy/chemoradiotherapy plus surgery (n = 5). Of the five patients who received salvage surgery, three underwent repeated resections. The potential benefit of multimodal salvage therapy was suggested in five patients (4 with chemotherapy/chemoradiotherapy plus surgery and 1 with chemoradiotherapy) who achieved durable disease control (cancer-specific survival from initial recurrence, 22-258 months). With a median follow-up of 25 months from recurrence, the 5-year cancer-specific survival rate was 58%. cancer-specific survival after recurrence was prolonged in patients with ≤ stage 3 disease, positive response to chemotherapy/chemoradiotherapy and salvage surgery. CONCLUSIONS: Long-term disease control and survival could be achieved in highly selected patients with recurrent adrenocortical carcinoma using a multidisciplinary approach. Patients who had relatively limited recurrent sites and responded well to chemotherapy/chemoradiotherapy may be considered for salvage surgery on a case-by-case basis.

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.

Association between immune-related adverse events and survival in patients with renal cell carcinoma treated with nivolumab plus ipilimumab: immortal time bias-corrected analysis.

BACKGROUND: Immune-related adverse events (irAEs) in patients treated with immune check inhibitors are associated with favourable response rate and survivals in multiple cancers, including renal cell carcinoma (RCC). The aim of this study was to investigate how irAEs were associated with improved survivals in advanced RCC patients treated with nivolumab plus ipilimumab. MATERIALS AND METHODS: This retrospective study included patients who received nivolumab plus ipilimumab at six centres, institutions, or hospitals between September 2018 and February 2022. We assessed associations of the development and the number of irAEs with overall survival (OS) and progression-free survival (PFS). To eliminate immortal time bias, landmark analysis and a Cox model with time-dependent variables were used. RESULTS: This study included 129 patients with a median follow-up of 12.3 months. The 2-year OS and PFS rates were 55% and 42%, respectively. Ninety six patients experienced irAEs. The development of irAEs was positively associated with OS and PFS rates (hazard ratio [HR] 0.328, 95% confidence interval [CI] 0.165-0.648, p = 0.001; HR 0.334, 95% CI 0.151-0.737, p = 0.007). Patients who experienced multiple irAEs had longer OS (HR 0.507, 95% CI 0.235-1.097, p = 0.085 or HR 0.245, 95% CI 0.110-0.544, p < 0.001) and PFS (HR 0.572, 95% CI 0.316-1.036, p = 0.085 or HR 0.267, 95% CI 0.113-0.628, p = 0.002) compared with those who experienced single or zero irAE. CONCLUSIONS: Developing irAEs, particularly multiple irAEs, is associated with favourable survivals in advanced RCC patients treated with nivolumab plus ipilimumab.

Clinical outcomes of nivolumab plus ipilimumab in patients with metastatic non-clear cell renal cell carcinoma: Real-world data from a Japanese multicenter retrospective study.

OBJECTIVES: Although nivolumab plus ipilimumab has become a standard treatment regimen for metastatic clear cell renal cell carcinoma (ccRCC), its efficacy in non-clear cell carcinoma (nccRCC) has not been fully examined. In the current study, we evaluated the clinical outcomes of nivolumab plus ipilimumab in nccRCC compared with ccRCC. METHODS: We retrospectively analyzed 22 patients with metastatic and/or locally advanced unresectable nccRCC who received nivolumab plus ipilimumab as a first-line therapy and compared them with 107 patients with ccRCC. Objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and toxicity were compared between the nccRCC and ccRCC groups. RESULTS: The histology of nccRCC included eight papillary, six unclassified, three chromophobe, two collecting duct carcinoma, and three other subtypes. Best objective response in nccRCC patients included three complete responses and five partial responses, resulting in an ORR of 36%, while that in ccRCC patients was 50% (p = 0.22). With a median follow-up of 11.9 months, OS was significantly shorter in patients with nccRCC than in those with ccRCC (median 20.8 months vs. not reached, p = 0.04), while there was no significant difference in PFS (median 6.3 vs. 10.8 months, p = 0.21). Treatment-related adverse events occurred in 14 (64%) nccRCC patients and 81 (76%) ccRCC patients. CONCLUSIONS: Combination treatment with nivolumab and ipilimumab demonstrated modest clinical efficacy in patients with nccRCC compared with patients with ccRCC, suggesting it could be a therapeutic option for metastatic nccRCC patients.

Preoperative testosterone and follicle stimulating hormone levels are important predictors for sperm retrieval by microdissection testicular sperm extraction in non-mosaic Klinefelter syndrome.

This study aimed to assess outcomes of microdissection testicular sperm extraction (MD-TESE) and identify predictors for sperm retrieval (SR) in patients with non-mosaic Klinefelter syndrome (NM-KFS). We retrospectively evaluated 37 patients with NM-KFS who underwent MD-TESE. Data of age at operation, body mass index (BMI), testicular volume, serum luteinizing hormone (LH), follicle stimulating hormone (FSH), preoperative and postoperative testosterone levels with reduction ratio between the two values, and FSH/preoperative testosterone ratio were analysed. These patients were divided into two groups according to success or failure of SR: the successful and failure groups. Factors related to SR were evaluated by statistical analyses using the Mann-Whitney U test and logistic regression modelling. Regarding these factors, the cut-off level was specified using the receiver operating characteristics (ROC) curve. Moreover, the percentage of SR at that level was assessed. A simple scoring model was developed based on the multivariate analysis. Fourteen patients underwent successful SR, whereas 23 experienced failure SR. Statistical analysis found preoperative testosterone and FSH levels to be significant factors associated with SR. On the ROC curve, the cut-off levels for preoperative testosterone and FSH were 2.34 ng/ml and 33.2 mIU/ml respectively. A new scoring model was developed, consisting of preoperative testosterone (≥2.34 ng/ml) and FSH (≤33.2 mIU/ml). The sperm retrieval rates (SRRs) were clearly discriminated by stratification according to the scoring model. The SRR of the cases of scores of 2, 1 and 0 were 87.5%, 31.6% and 10% respectively. At our hospital, the SRR of MD-TESE in patients with NM-KFS was 37.8%. The patients with high testosterone and low FSH levels tended to demonstrate successful SR.

Treatment strategies and outcomes in a long-term registry study of patients with high-risk metastatic hormone-naïve prostate cancer in Japan: An interim analysis of the J-ROCK study.

OBJECTIVE: The prognosis of high-risk metastatic hormone-naïve prostate cancer is poor, and real-world evidence of therapeutic options and sequences is lacking. The J-ROCK study aimed to evaluate the outcomes in a real-world setting in Japan. METHODS: Patients with high-risk metastatic hormone-naïve prostate cancer diagnosed after May 2019 were eligible. Based on their treatment within 3 months after diagnosis, patients were allocated to either cohort 1 (androgen deprivation therapy alone or combined androgen blockade with bicalutamide) or cohort 2 (androgen deprivation therapy with abiraterone acetate+prednisolone, docetaxel, enzalutamide, or apalutamide). RESULTS: In this first interim analysis (cut-off January 2021), 410 patients were enrolled, including 163 patients in cohort 1 and 247 in cohort 2. The median follow-up period was 7.6 (range 0.1-20.5) months. A higher proportion of patients in cohort 2 (42.5%) achieved nadir prostate-specific antigen levels ≤0.2 ng/ml within a year, compared with cohort 1 (22.1%). Prostate-specific antigen-progression-free survival was also more favorable in cohort 2 (adjusted hazard ratio 0.629 [95% confidence interval 0.345-1.147]). CONCLUSIONS: The higher proportion of cohort 2 suggest a paradigm shift has occurred in the real-world treatment of high-risk metastatic hormone-naïve prostate cancer in Japan. Some factors including prostate-specific antigen may affect treatment selection but need further observation. Most patients in cohort 2 received abiraterone acetate+prednisolone. The proportion of patients in cohort 1 receiving combined androgen blockade was lower than previously reported in Japan. This analysis suggest that more intensive therapy tends to prolong prostate-specific antigen-progression-free survival in patients with high-risk metastatic hormone-naïve prostate cancer.

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.

Early C-reactive protein kinetics predict survival of patients with advanced urothelial cancer treated with pembrolizumab.

OBJECTIVE: To assess the prognostic and predictive ability of early C-reactive protein (CRP) kinetics, dynamic changes in CRP levels, in patients with advanced urothelial cancer treated with pembrolizumab. PATIENTS AND METHODS: We retrospectively evaluated 97 patients with advanced urothelial cancer treated with pembrolizumab in second-line or later settings. Patients were divided into three early CRP kinetics groups: non-elevated (baseline CRP < 5 mg/L), responder (baseline CRP ≥ 5 mg/L and CRP decreased below baseline at least once within 30 days), and non-responder (baseline CRP ≥ 5 mg/L and CRP never decreased to baseline within 30 days). Association between early CRP kinetics and pembrolizumab efficacy including objective response rate (ORR), disease control rate (DCR), and overall survival (OS) were evaluated. RESULTS: Based on early CRP kinetics, 40, 27, and 30 patients were classified as non-elevated, responder, and non-responder, respectively. ORR and DCR were 33% and 60% in non-elevated, 30% and 48% in responder, and 17% and 40% in non-responder; without a statistically significant difference. OS was significantly different among the non-elevated, responder, and non-responder groups (p < 0.01), with 1-year survival rates of 69%, 61%, and 31%, respectively. Early CRP kinetics could discriminate the OS of patients without objective response. Non-responder was an independent predictor for OS (HR 3.65, p < 0.01), as well as liver metastasis and ECOG PS ≥ 2. CONCLUSION: Early CRP kinetics is associated with survival of advanced urothelial cancer patients treated with pembrolizumab and could be a potential biomarker for clinical benefit from immune checkpoint inhibitors.

Elevated preoperative C-reactive protein is associated with renal functional decline and non-cancer mortality in surgically treated renal cell carcinoma: analysis from the INternational Marker Consortium for Renal Cancer (INMARC).

OBJECTIVE: To investigate association of preoperative C-reactive protein (CRP) and non-cancer mortality (NCM) in a cohort of patients undergoing surgery for localised renal cell carcinoma (RCC). PATIENTS AND METHODS: Retrospective multicentre analysis of patients surgically treated for clinical Stage 1-2 RCC from 2006 to 2017, excluding all cases of cancer-specific mortality. Descriptive analyses were obtained between the pre-treatment normal-CRP (≤5 mg/L) and elevated-CRP (>5 mg/L) groups. The primary outcome was NCM. The secondary outcomes included progression to de novo chronic kidney disease Stages 3-4 (estimated glomerular filtration rate [eGFR] of <60, <45, and <30 mL/min/1.73 m2 ). Multivariable analyses (MVA) were performed to assess for risk factors associated with functional decline and NCM, and Kaplan-Meier analysis was used to obtain survival estimates for outcomes. RESULTS: A total of 1987 patients who underwent radical or partial nephrectomy were analysed (normal-CRP group, n = 963; elevated-CRP group, n = 1024). Groups were similar in age (59 vs 60 years, P = 0.079). An elevated CRP was more frequent in males (36.8% vs 27.8%, P < 0.001), African-Americans (22.6% vs 2.9%, P < 0.001), and in those with a higher median body mass index (30 vs 25 kg/m2 , P < 0.001) and larger median tumour size (4.5 vs 3.3 cm, P < 0.001). On MVA, an elevated CRP was independently associated with development of de novo eGFR of <60 mL/min/1.73 m2 (hazard ratio [HR] 1.32, P = 0.015), <45 mL/min/1.73 m2 (HR 1.41, P = 0.023) and <30 mL/min/1.73 m2 (odds ratio 2.23, P < 0.001). The MVA for factors associated with NCM demonstrated increasing age (HR 1.06, P < 0.001), preoperative elevated CRP (HR 2.18, P < 0.001) and an eGFR of <45 mL/min/1.73 m2 (HR 1.16; P = 0.021) as independent risk factors. Kaplan-Meier analysis revealed significantly higher 5-year NCM in the elevated-CRP group vs the normal-CRP group (98% vs 80%, P < 0.001). CONCLUSIONS: Pre-treatment elevated CRP was independently associated with both progressive renal functional decline and NCM in patients undergoing surgery for Stage 1-2 RCC. Patients with elevated CRP and Stage 1 and 2 RCC may be considered as having indication for nephron-sparing strategies, which may be prioritised if oncologically appropriate.

Potential of Perfusion Magnetic Resonance Imaging to Predict Residual Renal Function after Radical Nephroureterectomy.

INTRODUCTION: The diffusion-weighted imaging (DWI) technique with intravoxel incoherent motion model enables the estimation of capillary blood volume as a perfusion-related parameter- (PP-) value. Therefore, the PP-value of the kidney theoretically reflects renal capillary blood volume. We analyzed the usefulness of the PP-value in estimating postoperative renal function in upper-tract urothelial carcinoma (UTUC) patients. METHODS: Forty-eight consecutive patients who underwent magnetic resonance imaging before radical nephroureterectomy from 2011 to 2018 were analyzed. A PP-map displaying PP-values on a pixel-by-pixel basis was created from DWI signals (b-values of 0, 500, and 1,000 s/mm2). Two readers independently analyzed the renal PP-value. DWI-based split renal function (SRF) of the intact kidney was calculated by splitting serum Cr-based preoperative estimated glomerular filtration rates (eGFRs). The predictive accuracy of the method was evaluated using renography as the reference standard. RESULTS: Interobserver analysis revealed an excellent correlation value of 0.97. The SRF value showed a good linear correlation with the observed postoperative eGFR (r = 0.76, p < 0.001). The predictive accuracy of the DWI-based method was similar to that of the nuclear-based method. CONCLUSION: This DWI-based evaluation of capillary blood volume provides a noninvasive tool for predicting the postoperative renal function, thereby facilitating the management of UTUC patients.

Outcomes of gasless laparoendoscopic single-port partial nephrectomy in 356 consecutive patients: Feasibility of a clampless and sutureless technique.

OBJECTIVES: To investigate the outcomes and feasibilities of gasless laparoendoscopic single-port clampless sutureless partial nephrectomy. METHODS: We reviewed 356 consecutive patients with primary unilateral non-metastatic renal masses who underwent gasless laparoendoscopic single-port partial nephrectomy (2011-2018), which was performed retroperitoneally using a three-dimensional flexible endoscope, without vascular clamping or renorrhaphy in principle. RESULTS: The median tumor size was 2.5 cm, and 213 (60%), 105 (29%), and 38 (11%) patients had peripheral, central, and hilar tumors, respectively. Clampless and sutureless partial nephrectomy was accomplished in 337 patients (95%), while eight (2%) and 16 (4%) patients required vascular clamping and renorrhaphy, respectively. The median operative time and blood loss were 220 min and 266 mL, respectively; eight patients (2%) received blood transfusion. Clavien-Dindo grade 3a complications occurred in 27 patients (8%); all these patients had urinary leakage treated with ureteral stent placement, one of whom also developed a postoperative pseudoaneurysm. Among 324 patients diagnosed with renal cell carcinoma, six (2%) had positive surgical margins, and one (0.3%) and seven (2%) developed metastatic and local recurrences, respectively. During a median follow-up of 54 months, no patient died from kidney cancer. The median percent decrease in estimated glomerular filtration rate at 3 months after surgery was 5.7%. No patient experienced postoperative acute renal failure, while one patient with preexisting renal impairment started dialysis at 70 months after surgery. CONCLUSIONS: Clampless and sutureless partial nephrectomy can be safely accomplished in most patients undergoing gasless laparoendoscopic single-port surgery, yielding favorable oncological and functional outcomes.

Nonuse of antimicrobial prophylaxis in clean surgeries for adrenal and renal tumors: Results of the risk-based strategy in 1362 consecutive patients.

OBJECTIVES: To evaluate the incidence of perioperative infections without antimicrobial prophylaxis in patients undergoing clean surgeries for adrenal and renal tumors. METHODS: We prospectively enrolled 1362 consecutive patients who underwent minimally invasive adrenalectomy (n = 303), radical nephrectomy (n = 499), and partial nephrectomy (n = 560) using the gasless laparoendoscopic single-port surgery technique between 2005 and 2019. In 1059 patients, antimicrobial prophylaxis was not administered. The remaining 303 patients were considered at high risk for infection and received single-dose antimicrobial prophylaxis. The endpoint was the incidence of perioperative infections within 1 month from the surgery date. Perioperative infections were classified into surgical site infections, urinary tract infections, and remote infections. RESULTS: Seventy-four patients whose collecting systems were opened during partial nephrectomy were excluded, and the remaining 1013 patients with nonuse of antimicrobial prophylaxis and 275 patients with single-dose antimicrobial prophylaxis were retrospectively analyzed. The incidence of superficial surgical site infections, deep/organ-space surgical site infections, urinary tract infections, and remote infections was 1.6%, 0.7%, 2.8%, and 1.3%, respectively, in patients with nonuse of antimicrobial prophylaxis and 0.4%, 1.8%, 1.5%, and 1.5%, respectively, in patients with single-dose antimicrobial prophylaxis. All patients who developed perioperative infections were successfully treated. No clinical or surgical variables were significantly associated with the incidence of surgical site infections. One limitation of the present study was its nonrandomized and noncontrolled design. CONCLUSIONS: In minimally invasive clean surgeries for adrenal and renal tumors, antimicrobial prophylaxis is not necessary when individual risk of infection is considered low.

Renal epithelioid angiomyolipoma: Incidence in a Japanese cohort and diagnostic utility of diffusion-weighted magnetic resonance imaging.

OBJECTIVES: To show the epidemiological characteristics of epithelioid angiomyolipoma in a Japanese population, and to establish the preoperative diagnosis method of epithelioid angiomyolipoma. METHODS: Among the 855 tumors of patients who underwent partial/radical nephrectomy or renal biopsy for presumed renal cell carcinoma between 2007 and 2018, 39 renal tumors were diagnosed as nonclassical angiomyolipoma, including epithelioid angiomyolipoma and fat-poor angiomyolipoma. We retrospectively evaluated the incidence of epithelioid angiomyolipoma. Furthermore, we analyzed computed tomography and magnetic resonance imaging results, including diffusion-weighted magnetic resonance imaging findings of epithelioid angiomyolipoma and fat-poor angiomyolipoma. RESULTS: The incidence of epithelioid angiomyolipoma (n = 7) was 17.9% of surgically resected non-classical angiomyolipoma. The radiological appearance of epithelioid angiomyolipoma was hyperattenuating on unenhanced computed tomography images with iso or low intensity on T2-weighted magnetic resonance imaging. The mean apparent diffusion coefficient value of the solid component in epithelioid angiomyolipoma was significantly lower than that in fat-poor angiomyolipoma (median 0.79 × 10-3 vs 1.07 × 10-3 mm2 /s, P = 0.0019). CONCLUSIONS: The proportion of epithelioid angiomyolipoma in our Japanese cohort was equivalent to that of the reported series in the USA. The apparent diffusion coefficient value is potentially useful to differentiate between epithelioid angiomyolipoma and fat-poor angiomyolipoma. Further research is required to establish the imaging diagnostic criteria for epithelioid angiomyolipoma.

Value of extra-target prostate biopsy for the detection of magnetic resonance imaging-missed adverse pathology according to the Prostate Imaging Reporting and Data System scores: Spatial analysis using magnetic resonance-ultrasound fusion images.

OBJECTIVES: To clarify who benefits from extra-target sampling of systematic prostate biopsy to detect magnetic resonance imaging-missed significant cancer and upgrading, when concurrently carried out with magnetic resonance imaging-ultrasound fusion targeted biopsy. METHODS: Targeted biopsy and systematic biopsy were carried out in 301 men with Prostate Imaging Reporting and Data System scores ≥3. All score ≥3 regions were designated as targets. According to patients' highest Prostate Imaging Reporting and Data System scores, spatial relations between targets and biopsy-proven cancer were investigated to identify magnetic resonance imaging-missed pathology. RESULTS: Overall, targeted biopsy and systematic biopsy detected significant cancer in 56.5% and 46.5%, respectively (P < 0.001). Significant cancer was detected only by systematic biopsy in 7.0%, and only outside targets in 5.0%. Upgrading by systematic biopsy was observed in 16.3%, and occurred outside targets in 11.0%. On multivariate analysis, the highest Prostate Imaging Reporting and Data System 4 was predictive for significant cancer only outside targets (odds ratio 5.81, P = 0.002) and for upgrading derived from outside targets (odds ratio 2.64, P = 0.012). According to the scores of 3, 4 and 5, significant cancer was identified only outside targets in 1.0%, 11.2% and 2.9%, respectively (P = 0.003 for Prostate Imaging Reporting and Data System 3 vs 4; P = 0.019 for Prostate Imaging Reporting and Data System 4 vs 5), and upgrading occurred in 6.1%, 18.4% and 8.6%, respectively (P = 0.009 and 0.040). CONCLUSIONS: Men with the highest Prostate Imaging Reporting and Data System score 4 receive the largest benefit from extra-target biopsy for magnetic resonance imaging-missed significant cancer detection and upgrading. In men with a score of 3, less adverse pathology is missed without extra-target biopsy. These findings suggest prostate biopsy strategy could be tailored according to Prostate Imaging Reporting and Data System scores.