Follow-up strategies after trimodal treatment for muscle-invasive bladder cancer: a systematic review.

PURPOSE: Optimal follow-up strategies following trimodal treatment for muscle invasive bladder cancer play a crucial role in detecting and managing relapse and side-effects. This article provides a comprehensive summary of the patterns and risk factors of relapse, functional outcomes, and follow-up protocols. METHODS: A systematic literature search on PubMed and review of current guidelines and institutional follow-up protocols after trimodal therapy were conducted. RESULTS: Out of 200 identified publications, 43 studies (28 retrospective, 15 prospective) were selected, encompassing 7447 patients (study sizes from 24 to 728 patients). Recurrence rates in the urinary bladder varied between 14-52%; 3-16% were muscle-invasive while 11-36% were non-muscle invasive. Nodal recurrence occurred at 13-16% and distant metastases at 15-35%. After 5 and 10 years of follow-up, around 60-85% and 45-75% of patients could preserve their bladder, respectively. Various prognostic risk factors associated with relapse and inferior survival were proposed, including higher disease stage (> c/pT2), presence of extensive/multifocal carcinoma in situ (CIS), hydronephrosis, multifocality, histological subtypes, incomplete transurethral resection of bladder tumor (TURBT) and incomplete response to radio-chemotherapy. The analyzed follow-up guidelines varied slightly in terms of the number, timing, and types of investigations, but overall, the recommendations were similar. CONCLUSION: Randomized prospective studies should focus on evaluating the impact of specific follow-up protocols on oncological and functional outcomes following trimodal treatment for muscle-invasive bladder cancer. It is crucial to evaluate personalized adaption of follow-up protocols based on established risk factors, as there is potential for improved patient outcomes and resource allocation.

Why Do Men Reject Adjuvant Radiotherapy following Radical Prostatectomy? A Systematic Survey.

INTRODUCTION: The aim of this study was to investigate non-adherence rates to adjuvant radiotherapy (aRT) after radical prostatectomy (RP) and to obtain patient reported reasons for rejecting aRT despite recommendation by a multidisciplinary team discussion (MTD). METHODS: In a retrospective monocentric analysis, we identified 1,197 prostate cancer patients who underwent RP between 2014 and 2022 at our institution, of which 735 received a postoperative MTD recommendation. Patients with a recommendation for aRT underwent a structured phone interview with predefined standardised qualitative and quantitative questions and were stratified into "adherent" (aRT performed) and "non-adherent" groups (aRT not performed). RESULTS: Of 55 patients receiving a recommendation for aRT (7.5% of all RP patients), 24 (44%) were non-adherent. Baseline tumour characteristics were comparable among the groups. "Fear of radiation damage" was the most common reason for rejection, followed by "lack of information," "feeling that the treating physician does not support the recommendation" and "the impression that aRT is not associated with improved oncological outcome." Salvage radiotherapy was performed in 25% of non-adherent patients. CONCLUSION: High rates of non-adherence to aRT after RP were observed, and reasons for this phenomenon are most likely multifactorial. Multidisciplinary and individualized patient counselling might be a key for increasing adherence rates.

Solitary Fibrous Tumor of the Prostate Treated with Frozen-Section Supported Robot-Assisted Nerve-Sparing Radical Prostatectomy.

INTRODUCTION: Solitary fibrous tumors (SFTs) of the prostate are extremely rare. We report on a 60-year-old man who was diagnosed with prostatic SFT through transurethral resection (TUR) of the prostate, and we provide a narrative literature review to put the case into perspective. We looked into multiple databases for articles published before June 2022. CASE REPORT: A 60-year-old man without comorbidities presented with acute urinary retention and significant macrohematuria. Due to recurrent bladder tamponades and relevant blood loss despite irrigation, an emergency endoscopic transurethral evaluation was initiated. Intraoperatively, diffuse venous hemorrhage from prostatic vessels around the bladder neck was detected, as well as significant hemorrhage from a grossly enlarged and tumor-suspicious prostate middle lobe. Within the framework of extensive bipolar coagulation, parts of the suspicious middle lobe were removed via TUR. The final histopathology report showed incompletely resected SFT of the prostate. Due to the extremely rare SFT diagnosis, the case was discussed in an interdisciplinary tumor board and further diagnostic workup, including thoracoabdominal computed tomography and magnetic resonance imaging of the pelvis, was performed, which revealed no secondary tumors or signs of metastasis. According to the tumor board recommendation, robot-assisted radical prostatectomy (RARP) with bilateral nerve sparing was performed, supported by intraoperative frozen section. The final histopathology confirmed the SFT that had developed from the transition zone. The SFT was resected with negative frozen section result and negative surgical margins (R0). No intra- and perioperative complications occurred, and in the short-term follow-up, the patient presented in excellent general status with full continence. From 1997 to June 2022, we identified a total of 12 publications reporting on treatment for prostatic SFT (11 case reports and 2 patient series), with none performing bilateral nerve sparing, frozen section, or robot-assisted radical prostatectomy. No common survival endpoints were accessible. CONCLUSION: This case demonstrates the exceedingly rare case of SFT of the prostate, which has been described in the literature in only 23 men worldwide. Here, we were the first to demonstrate the feasibility of bilateral nerve-sparing RARP supported by frozen section. A systematic review was not possible due to the lack of common endpoints.

An Algorithm to Personalize Nerve Sparing in Men with Unilateral High-Risk Prostate Cancer.

PURPOSE: Current guidelines do not provide strong recommendations on preservation of the neurovascular bundles during radical prostatectomy in case of high-risk (HR) prostate cancer and/or suspicious extraprostatic extension (EPE). We aimed to evaluate when, in case of unilateral HR disease, contralateral nerve sparing (NS) should be considered or not. MATERIALS AND METHODS: Within a multi-institutional data set we selected patients with unilateral HR prostate cancer, defined as unilateral EPE and/or seminal vesicle invasion (SVI) on multiparametric (mp) magnetic resonance imaging (MRI), or unilateral International Society of Urologic Pathologists (ISUP) 4-5 or prostate specific antigen ≥20 ng/ml. To evaluate when to perform NS based on the risk of contralateral EPE, we relied on chi-square automated interaction detection, a recursive machine-learning partitioning algorithm developed to identify risk groups, which was fit to predict the presence of EPE on final pathology, contralaterally to the prostate lobe with HR disease. RESULTS: A total of 705 patients were identified. Contralateral EPE was documented in 87 patients (12%). Chi-square automated interaction detection identified 3 groups, consisting of 1) absence of SVI on mpMRI and index lesion diameter ≤15 mm, 2) index lesion diameter ≤15 mm and contralateral ISUP 2-3 or index lesion diameter >15 mm and negative contralateral biopsy or ISUP 1, and 3) SVI on mpMRI or index lesion diameter >15 mm and contralateral biopsy ISUP 2-3. We named those groups as low, intermediate and high-risk, respectively, for contralateral EPE. The rate of EPE and positive surgical margins across the groups were 4.8%, 14% and 26%, and 5.6%, 13% and 18%, respectively. CONCLUSIONS: Our study challenges current guidelines by proving that wide bilateral excision in men with unilateral HR disease is not justified. Pending external validation, we propose performing NS and incremental NS in case of contralateral low and intermediate EPE risk, respectively.

Minimally invasive retroperitoneal lymph node dissection for men with testis cancer: a retrospective cohort study of safety and feasibility.

PURPOSE: To describe the perioperative safety, functional and immediate post-operative oncological outcomes of minimally invasive RPLND (miRPLND) for testis cancer. METHODS: We performed a retrospective multi-centre cohort study on testis cancer patients treated with miRPLND from 16 institutions in eight countries. We measured clinician-reported outcomes stratified by indication. We performed logistic regression to identify predictors for maintained postoperative ejaculatory function. RESULTS: Data for 457 men undergoing miRPLND were studied. miRPLND comprised laparoscopic (n = 56) or robotic (n = 401) miRPLND. Indications included pre-chemotherapy in 305 and post-chemotherapy in 152 men. The median retroperitoneal mass size was 32 mm and operative time 270 min. Intraoperative complications occurred in 20 (4%) and postoperative complications in 26 (6%). In multivariable regression, nerve sparing, and template resection improved ejaculatory function significantly (template vs bilateral resection [odds ratio (OR) 19.4, 95% confidence interval (CI) 6.5-75.6], nerve sparing vs non-nerve sparing [OR 5.9, 95% CI 2.3-16.1]). In 91 men treated with primary RPLND, nerve sparing and template resection, normal postoperative ejaculation was reported in 96%. During a median follow-up of 33 months, relapse was detected in 39 (9%) of which one with port site (< 1%), one with peritoneal recurrence and 10 (2%) with retroperitoneum recurrences. CONCLUSION: The low proportion of complications or peritoneal recurrences and high proportion of men with normal postoperative ejaculatory function supports further miRPLND studies.

Carboplatin-based adjuvant chemotherapy versus observation after radical cystectomy in patients with pN1-3 urothelial bladder cancer.

PURPOSE: To test the impact of carboplatin-based ACT on overall survival (OS) in patients with pN1-3 cM0 BCa. METHODS: A retrospective analysis was conducted on 1057 patients with pTany pN1-3 cM0 urothelial BCa treated with or without carboplatin-based ACT after radical cystectomy and bilateral lymph-node dissection between 2002 and 2018 at 12 European and North-American hospitals. No patient received neoadjuvant chemotherapy or radiation therapy. Only patients with negative surgical margins at surgery were included. A 3:1 propensity score matching (PSM) was performed using logistic regression to adjust for baseline characteristics. Univariable and multivariable Cox regression analyses were used to predict the effect of carboplatin-based ACT on OS. The Kaplan-Meier method was used to display OS in the matched cohort. RESULTS: Of the 1057 patients included in the study, 69 (6.5%) received carboplatin-based ACT. After PSM, 244 total patients were identified in two cohorts that did not differ for baseline characteristics. Death was recorded in 114 (46.7%) patients over a median follow-up of 19 months. In the multivariable Cox regression analyses, increasing age at surgery (hazard ratio [HR] 1.02, 95% confidence interval [CI] 1.01-1.06, p < 0.001) and increasing number of positive lymph nodes (HR 1.06, 95% CI 1.01-1.07, p = 0.02) were independent predictors of worse OS. The delivery of carboplatin-based ACT was not predictive of improved OS (HR 0.67, 95% CI 0.43-1.04, p = 0.08). The main limitations of this study are its retrospective design and the relatively low number of patients involved. CONCLUSIONS: Carboplatin-based might not improve OS in patients with pN1-3 cM0 BCa. Our results underline the need for alternative therapies for cisplatin-ineligible patients.

Immediate radical cystectomy versus BCG immunotherapy for T1 high-grade non-muscle-invasive squamous bladder cancer: an international multi-centre collaboration.

PURPOSE: To compare cancer-specific mortality (CSM) and overall mortality (OM) between immediate radical cystectomy (RC) and Bacillus Calmette-Guérin (BCG) immunotherapy for T1 squamous bladder cancer (BCa). METHODS: We retrospectively analysed 188 T1 high-grade squamous BCa patients treated between 1998 and 2019 at fifteen tertiary referral centres. Median follow-up time was 36 months (interquartile range: 19-76). The cumulative incidence and Kaplan-Meier curves were applied for CSM and OM, respectively, and compared with the Pepe-Mori and log-rank tests. Multivariable Cox models, adjusted for pathological findings at initial transurethral resection of bladder (TURB) specimen, were adopted to predict tumour recurrence and tumour progression after BCG immunotherapy. RESULTS: Immediate RC and conservative management were performed in 20% and 80% of patients, respectively. 5-year CSM and OM did not significantly differ between the two therapeutic strategies (Pepe-Mori test p = 0.052 and log-rank test p = 0.2, respectively). At multivariable Cox analyses, pure squamous cell carcinoma (SqCC) was an independent predictor of tumour progression (p = 0.04), while concomitant lympho-vascular invasion (LVI) was an independent predictor of both tumour recurrence and progression (p = 0.04) after BCG. Patients with neither pure SqCC nor LVI showed a significant benefit in 3-year recurrence-free survival and progression-free survival compared to individuals with pure SqCC or LVI (60% vs. 44%, p = 0.04 and 80% vs. 68%, p = 0.004, respectively). CONCLUSION: BCG could represent an effective treatment for T1 squamous BCa patients with neither pure SqCC nor LVI, while immediate RC should be preferred among T1 squamous BCa patients with pure SqCC or LVI at initial TURB specimen.

Assessment of the Anastomosis after Radical Prostatectomy: A Review of Available Diagnostic Methods.

INTRODUCTION: After radical prostatectomy, many institutions perform cystography to exclude vesicourethral anastomotic leakage before removing a urethral catheter. We reviewed diagnostic methods to exclude leakage compared to the reference standard cystography. METHODS: We performed systematic literature review to summarize the published options and outcomes for assessment of vesicourethral anastomotic leakage after radical prostatectomy. RESULTS: Of 2,137 publications, 45 full-text manuscripts underwent full-text screening, of which 9 studies contributing 919 patients were included. Seven studies described ultrasound-guided assessment (four transrectal, two transabdominal, one transperineal). Two further studies described the use of computerized tomography. Ultrasound-guided assessment of the anastomosis after radical prostatectomy shows promising agreement with cystography. Computerized tomography-aided assessment of vesicourethral anastomosis detects more leakages; however, clinical consequences are not defined. CONCLUSION: Further studies are warranted to (1) identify men at risk of anastomotic leakage who should undergo assessment before trial without a catheter and (2) provide prospective comparisons of different ultrasound-guided approaches.

Postoperative peripheral neuropathies associated with patient positioning during robot-assisted laparoscopic radical prostatectomy (RARP): A systematic review of the literature.

OBJECTIVE: To perform a systematic review of the literature concerning postoperative peripheral neuropathies associated with patient positioning during robot-assisted laparoscopic radical prostatectomy (RARP). PATIENTS AND METHODS: A systematic review on articles published from January 1, 1990 to March 15, 2020 was performed in accordance with the PRISMA declaration (Preferred Reporting Items for Systematic Reviews and Meta-Analysis). The electronic search was done searching through the Cochrane Registry, PubMed/EMBASE, Medline, and Scopus. Relevant papers addressing postoperative peripheral neuropathies related to patient positioning during RARP were integrated into the analyses. RESULTS: After screening 4975 articles, one randomized controlled trial and five retrospective studies with a total of 63,667 patients were included in this review. Peripheral neuropathies of the upper extremities were documented in three articles with a total of 15 patients, peripheric neuropathies of the lower extremities were reported in five articles with a total of 76 patients. Analysis of the data was exploratory, since screening techniques, systematically reporting, and description of positioning techniques was not standardized or not reported. CONCLUSIONS: The incidence of peripheral neuropathies at RARP varies between 1.3% and 10.8%. Lower extremities are more affected than upper extremities and the most important risk factors are intraoperative time duration, patients comorbidities, and ASA score. High-quality prospective randomized studies to better assess the impact of patient positioning during RARP on the development postoperative peripheral neuropathies are needed.

Oncologic Surveillance for Variant Histology Bladder Cancer after Radical Cystectomy.

PURPOSE: Presently, major guidelines do not provide specific recommendations on oncologic surveillance for patients who harbor variant histology (VH) bladder cancer (BCa) at radical cystectomy. We aimed to create a personalized followup scheme that dynamically weighs other cause mortality (OCM) vs the risk of recurrence for VH BCa, and to compare it with a similar one for pure urothelial carcinoma (pUC). MATERIALS AND METHODS: Within a multi-institutional registry, 528 and 1,894 patients with VH BCa and pUC, respectively, were identified. The Weibull regression was used to detect the time points after which the risk of OCM exceeded the risk of recurrence during followup. The risk of OCM over time was stratified based on age and comorbidities, and the risk of recurrence on pathological stage and recurrence site. RESULTS: Individuals with VH had a higher risk of recurrence (recurrence-free survival 30% vs 51% at 10 years, p <0.001) and shorter median time to recurrence (88 vs 123 months, p <0.01) relative to pUC. Among VH, micropapillary variant conferred the greatest risk of recurrence on the abdomen and lungs, and mixed variants carried the greatest risk of metastasizing to bones and other sites compared to pUC. Overall, surveillance should be continued for a longer time for individuals with VH BCa. Notably, patients younger than 60 years with VH and pT0/Ta/T1/N0 at radical cystectomy should continue oncologic surveillance after 10 years vs 6.5 years for pUC individuals. CONCLUSIONS: VH BCa is associated with greater recurrence risk than pUC. A followup scheme that is valid for pUC should not be applied to individuals with VH. Herein, we present a personalized approach for surveillance that may allow an improved shared decision.

Trends in risk-group distribution and Pentafecta outcomes in patients treated with nerve-sparing, robot-assisted radical prostatectomy: a 10-year low-intermediate volume single-center experience.

PURPOSE: To evaluate the trends in risk-group distribution and Pentafecta outcomes in patients treated with nerve-sparing (NS), robot-assisted radical prostatectomy (RARP) in a single low-intermediate volume prostate cancer (PCa) center over a 10-year period. MATERIALS AND METHODS: We queried a prospectively maintained database for patients who underwent NS RARP between 2009 and 2018 in a low-intermediate volume PCa center. Risk-groups were defined according to the D'Amico classification. Pentafecta outcomes referred to the postsurgical presence of potency and continence, and the absence of biochemical recurrence (BCR), positive surgical margins (PSM), and perioperative complications. The Kruskall-Wallis test, the t test and the Mann-Whitney tests were used when appropriate. RESULTS: 603 patients underwent NS RARP and 484 patients were evaluated for Pentafecta outcomes. Median postsurgical follow-up was 28 months. Overall, 137 (22.7%), 376 (62.3%), and 90 (15%) patients were diagnosed in the low-, intermediate-, and high-risk groups, respectively. Patients undergoing NS RARP shifted from 33 to 20% in the low-risk group, from 52 to 62% in the intermediate-risk group, and from 10 to 13% in the high-risk group. Patients reaching Pentafecta increased from 38 to 44%. No postoperative potency was the main reason for non-achieving Pentafecta (71%). BCR strongly limited Pentafecta achievement in the high-risk group (61%), but not in intermediate (24%) and low-risk (30%) groups. CONCLUSIONS: Low-intermediate volume PCa centers show similar trends to high-volume centers regarding risk group distributions over time in PCa patients undergoing NS RARP. We reported an increase in Pentafecta outcomes achievement over time even for experienced surgeons. Pentafecta outcomes achievement is risk-group dependent.

The impact of preoperative nutritional status on post-surgical complication and mortality rates in patients undergoing radical cystectomy for bladder cancer: a systematic review of the literature.

PURPOSE: To investigate the impact of preoperative nutritional factors [body mass index (BMI)], hypoalbuminemia (< 3.5 g/dL, sarcopenia) on complication and mortality rates after radical cystectomy (RC) for bladder cancer. METHODS: The PubMed database was systematically searched for studies investigating the effect of nutritional status on postoperative outcomes after RC. English-language articles published between March 2010 and March 2020 were reviewed. For statistical analyses odds ratios (ORs) and hazard ratios (HRs) weighted mean was applied. RESULTS: Overall, 81 studies were included. Twenty-nine studies were enrolled in the final analyses. Patients with a 25-29.9 kg/m2 BMI (OR 1.55, 95% confidence interval [CI] 1.14-2.07) and those with a BMI ≥ 30 kg/m2 (OR 1.73, 95% CI 1.29-2.40) had a significantly increased risk of 30 day complications after RC. Preoperative hypoalbuminemia increased the risk of 30 day complications (OR 1.56, 95% CI 1.07-2.35); it was a predictor of worse 3 year overall survival (OS) (HR 1.86, 95% CI 1.32-2.66). Sarcopenic patients had a higher risk of 90 day complications than non-sarcopenic ones (OR 2.49, 95% CI 1.22-5.04). Sarcopenia was significantly associated with unfavorable 5 year cancer-specific survival (CSS) (HR 1.73, 95% CI 1.07-2.80), and OS (HR 1.60, 95% CI 1.13-2.25). CONCLUSION: High BMI, hypoalbuminemia, and sarcopenia significantly increased the complication rate after RC. Hypoalbuminemia predicted worse 3 year OS and sarcopenia predicted unfavorable 5 year CSS and OS. Preoperative assessment of RC patients' nutritional status is a useful tool to predict perioperative and survival outcomes.

Adjuvant chemotherapy is ineffective in patients with bladder cancer and variant histology treated with radical cystectomy with curative intent.

OBJECTIVES: Adjuvant chemotherapy (ACT) is recommended for non-organ-confined bladder cancer (BCa) after radical cystectomy (RC) and pelvic lymph node dissection (PLND), but there are sparse data regarding its specific efficacy in patients with histological variants. The aim of our study was to evaluate the role of ACT on survival outcomes in patients with variant histology in a large multicenter cohort. MATERIALS AND METHODS: We retrospectively evaluated data of 3963 patients with BCa treated with RC and bilateral PLND with curative intent at several institutions between 1999 and 2018. The histological type was classified into six groups: pure urothelial carcinoma (PUC) or squamous, sarcomatoid, micropapillary, glandular and neuroendocrine differentiation. Multivariable competing risk analysis was applied to assess the role of ACT on recurrence and cancer-specific mortality (CSM) in each histological subtype. RESULTS: Of the 3963 patients included in the study, 23% had variant histology at RC specimen and 723 (18%) patients received ACT. ACT was found to be significantly associated with reduced risk of recurrence (sub-hazard ratio [SHR]: 0.55, confidence interval [CI] 0.42-0.71, p < 0.001) and CSM (SHR: 0.58, CI 0.44-0.78, p < 0.001) in the PUC only, while no histological subtype received a significant benefit on survival outcomes (all p > 0.05) from administration of ACT. The limitation of the study includes the retrospective design, the lack of a central pathology review and the number of ACT cycles. CONCLUSION: In our study, the administration of ACT was associated with improved survival outcomes in PUC only. No histological subtype found a benefit in overall recurrence and CSM from ACT.

The impact of treatment modality on survival in patients with clinical node-positive bladder cancer: results from a multicenter collaboration.

PURPOSE: To assess the impact of perioperative chemotherapy on survival in cN+ BCa patients and analyze it according to the pN status. METHODS: A retrospective analysis was conducted on 639 BCa patients with cTanyN1-3M0 BCa treated with radical cystectomy (RC) and bilateral lymph node dissection (LND) with or without perioperative chemotherapy in ten tertiary referral centers from 1990 to 2017. Selected cN+ patients received induction chemotherapy (IC), whereas adjuvant chemotherapy (ACT) was delivered to selected pN+ patients. Univariable and multivariable Cox regression analyses were used to predict overall mortality (OM) after surgery, adjusting for clinicopathological confounders. Kaplan-Meier analyses assessed OM according to the treatment modality. RESULTS: Overall, 356 (56%) patients were treated with surgery alone, 155 (24%) with IC followed by surgery, and 128 (20%) with ACT following surgery. Over a median follow-up of 25 months, 316 deaths were recorded. At univariable analysis, patients treated with IC and surgery had lower OM both considering cN+ [hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.49-0.87, p = 0.004] and cN+pN- patients (HR 0.61, 95% CI 0.37-0.99, p = 0.05) compared to those treated with surgery alone. cN+pN+ patients treated with ACT experienced lower OM compared to those treated with IC or surgery alone at multivariable analysis (HR 0.40, 95% CI 0.22-0.74, p = 0.003). CONCLUSION: Patients with cTany cN+ cM0 BCa benefit more in terms of OS when treated with IC followed by RC + LND compared to RC + LND alone, regardless of LNMs at final histopathology examination. More data are needed to assess the role of ACT in the management of cN+ patients.

How to improve patient selection for neoadjuvant chemotherapy in bladder cancer patients candidate for radical cystectomy and pelvic lymph node dissection.

PURPOSE: To improve patient selection for neoadjuvant chemotherapy (NAC) before radical cystectomy (RC) in bladder cancer patients (BCa). METHODS: Retrospective evaluation of 1057 patients with cT2-4N0M0 BCa treated with RC and pelvic lymph node dissection between 1990 and 2018 at 3 referral centers. Adverse pathologic features (APF) were defined as pT3-pT4/pN + disease at RC. A regression tree model (CART) was used to assess preoperative risk group classes. A multivariable logistic regression (MVA) was performed to identify predictors of APF at RC. RESULTS: Median age was 70 years and most of the patients were men (83%). Of the 1057 patients included in our study, 688 (65%) had APF. CART analysis was able to stratify patients into 3 risk groups: low (cT2 and single disease, odds ratio [OR] 0.62), intermediate (cT2 and multiple disease, OR 1.08), and high (cT3-cT4, OR 1.28). On MVA APF were associated with variant histology (odds ratio [OR] 3.97, 95% confidence interval [CI] 1.46-10.83, p = 0.007), multifocality at TUR (OR 2.56, CI 1.27-5.17, p = 0.09), completeness of resection (OR 0.47, CI 0.23-0.96, p = 0.04) and clinical extravesical disease (OR 3.42, CI 1.63-7.14, p = 0.001). CONCLUSION: We defined three pre-operative risk classes. Our results indicate that patients with a cT3-T4 disease are those who might benefit more from NAC whereas those with T2 single disease should be those to whom NAC probably shouldn't be proposed. Given the high rate of understaging in BCa patients, NAC can be proposed in selected cases of cT2/multifocal disease.

Incidence and survival outcomes in patients with upper urinary tract urothelial carcinoma diagnosed with variant histology and treated with nephroureterectomy.

OBJECTIVE: To evaluate the incidence and survival outcomes of histological variants of upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU). MATERIALS AND METHODS: We retrospectively analysed data from 1610 patients treated with RNU for clinically non-metastatic UTUC between 1990 and 2016 in several centres participating in the UTUC Collaboration. Histological variants were classified as micropapillary, squamous, sarcomatoid and other, including other rare variants (<10 cases for each). Multivariable competing risk analyses were conducted to assess the effect of variant histology on overall recurrence and cancer-specific mortality (CSM). RESULTS: Overall, 1460 patients (91%) had pure urothelial carcinoma (PUC), whereas 150 (9%) were diagnosed with a variant histology, including 89 (5.0%), 41 (2.0%), 10 (1.0%) and 10 (1.0%) cases of micropapillary, squamous, sarcomatoid and other tumours, respectively. Variant histology was associated with the presence of adverse pathological features compared with PUC, including non-organ-confined disease (59% vs 38%; P < 0.001), lymph node invasion (28% vs 24%; P = 0.02), high-grade disease (88% vs 71%; P < 0.001), tumour necrosis (28% vs 16%; P = 0.001) and positive surgical margins (15% vs 8%; P = 0.01). In competing risk analysis, micropapillary variant was the only factor associated with worse recurrence (sub-hazard ratio [SHR] 2.27, 95% confidence interval [CI] 1.25-4.79; P = 0.02) whereas sarcomatoid variant was associated with worse CSM (SHR 16.8, 95% CI 6.86-41.17; P < 0.001). CONCLUSION: We found that one out of 10 patients with UTUC treated with RNU had variant histology. Only micropapillary and sarcomatoid variants were associated with poorer oncological outcomes after adjusting for available confounding factors.

Differences in trends in the use of robot-assisted and open radical cystectomy and changes over time in peri-operative outcomes among selected centres in North America and Europe: an international multicentre collaboration.

OBJECTIVES: To compare trends in the use of robot-assisted radical cystectomy (RARC) and changes over time in peri-operative outcomes in selected North American and European centres. MATERIALS AND METHODS: We conducted a retrospective evaluation of 2401 patients treated with open radical cystectomy (ORC) or RARC for bladder cancer at 12 centres in North America and Europe between 2006 and 2018. We used the Kruskal-Wallis and chi-squared test to evaluate differences between continuous and categorical variables. RESULTS: Overall, 49.5% of patients underwent RARC and 51.5% ORC. RARC became the most commonly performed procedure in contemporary patients, with an increase from 29% in 2006-2008 to 54% in 2015-2018 (P < 0.001). In the North American centres the use of RARC was higher than that of ORC from 2006, and remained stable over time, whereas in the European centres its use increased exponentially from 2% to 50%. In both groups patients who underwent RARC had less advanced T stages (P < 0.001), lower American Society of Anesthesiologists scores (P < 0.05), lower blood loss (P = 0.001) and shorter length of hospital stay (P < 0.05). No differences were found in early complications. Early readmission and re-operation rates were worse for patients treated with RARC in the European centres; however, when contemporary patients only were considered, the statistical significance was lost. CONCLUSION: The present study shows that the use of RARC has constantly increased since its introduction, overtaking ORC in the most contemporary series. While RARC was more frequently performed than ORC since its introduction in the North American centres and its use remained substantially stable over time, its use increased exponentially in the European centres. The different trends in use of RARC/ORC and changes over time in peri-operative outcomes between the North American and European centres can be attributed to the earlier introduction and spread of RARC in the former compared with the latter.

The effect of androgen deprivation treatment on subsequent risk of bladder cancer diagnosis in male patients treated for prostate cancer.

INTRODUCTION: Bladder cancer (BCa) is three-to-four times more common in men than in women. To explain this gender gap, several theories have been proposed, including the impact of androgen hormones. The aim of this study was to investigate the differential impact of androgen deprivation therapy (ADT) on subsequent risk of developing BCa in men with prostate cancer (PCa). METHODS: A total of 196,914 patients diagnosed with histologically confirmed localized PCa between 2000 and 2009 were identified in the SEER-Medicare insurance program-linked database. Competing-risk regression analyses were performed to assess the risk of developing BCa adjusting for the risk of all-cause mortality. Univariable and multivariable competing-risk regression analyses were performed to test the effect of ADT on BCa incidence for each PCa treatment modality. RESULTS: Of the 196,914 individuals included in the study, 68,421 (34.7%) received ADT. Median (IQR) follow-up was 59 (29-95) months. Overall, a total of 2495 (1.3%) individuals developed BCa during follow-up. After stratification according to ADT, the 10-year cumulative incidence rate was 1.75% (95% CI 1.65-1.85). In the untreated group, the 10-year cumulative incidence rate was 1.99% (95% CI 1.83-2.15). In multivariable competing-risk regression, the use of ADT was not associated with BCa, after accounting for the risk of dying from any cause (p = 0.1). CONCLUSION: We failed to identify any impact of ADT on the risk of developing a subsequent BCa even after stratifying according to the type of treatment. Further studies are required to explain the gender gap in BCa incidence and outcomes.