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Objective To assess whether bacillus Calmette-Guerin (BCG) responsiveness after initiation of an adequate BCG treatment (at least five of six instillations of induction and at least two of three instillations of maintenance) impacts oncological outcomes in patients with carcinoma in situ (CIS) of the bladder treated with BCG immunotherapy. Patients and Methods Data were available for 193 patients with bladder CIS with or without associated cTa/cT1 disease who received an adequate BCG treatment between 2008 and 2015. Bladder biopsies were taken at 6 months and patients were then stratified as either BCG responsive (negative biopsies) or BCG unresponsive (positive biopsies). Inverse probability weighting (IPW)-adjusted Kaplan-Meier and IPW-adjusted Cox regression were performed to compare progression-free survival (PFS), radical cystectomy-free survival (RCFS), overall survival OS, and cancer-specific survival (CSS) in the two groups. Results and Limitations Comparing the BCG-responsive and BCG-unresponsive groups, IPW-adjusted Kaplan-Meier analysis revealed, respectively, a median (interquartile range) of PFS of 9 (5-15) vs 48.5 (28-77) months (P = 0.001), a RCFS of 11 (9-15) vs 49 (24-76) months (P < 0.001), and a CSS of 25 (13-60) vs 109 (78-307) months (P = 0.004). On IPW-adjusted Cox regression analysis, BCG-unresponsive patients had a worse PFS (hazard ratio [HR] 3.40, 95% confidence interval [CI] 1.59-7.27), RCFS (HR 3.52, 95% CI 1.77-7), and CSS (HR 4.42, 95% CI 1.95-10.01). We found no significant differences for OS. Conclusion Using an IPW method we found that lack of response after initiation of an adequate BCG treatment has prognostic implications beyond identification of complete response in patients with CIS. BCG-unresponsive patients, satisfying the novel definition of BCG unresponsive, showed a poor PFS, RCFS, and CSS. In this setting, the patients should be counselled regarding RC as a first option or enrolled in a clinical trial if they refuse RC or are unfit for surgery.

Background: It has been proposed that en bloc resection of bladder tumor (ERBT) improves the quality of tumor resection. A recent international collaborative consensus statement on ERBT underlined the lack of high-quality prospective studies precluding the achievement of solid conclusion on ERBT.Objective: To compare conventional transurethral resection of bladder tumor (cTURBT) and ERBT.Design, setting, and participants: This study (NCT04712201) was a prospective, randomized, noninferiority trial enrolling patients diagnosed with bladder cancer (BC) undergoing endoscopic intervention. Inclusion criteria were: tumor size 0.05). The recurrence rate at median follow-up of 15 mo (interquartile range 7-28) was 18% for cTURBT versus 13% for ERBT (p = 0.16). Limitations include the single high-volume institution and the short-term follow-up. Conclusions: Our study has the highest level of evidence for comparison of ERBT versus TURBT. ERBT was noninferior to TURBT for BC staging. The rate of T1 substaging feasibilityPatient summary: We compared two techniques for removing tumors from the bladder. The en bloc technique removes the tumor in one piece and is not inferior to the conventional method in terms of the quality of the surgical resection and cancer staging assessment. (c) 2022 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Simple Summary:& nbsp;This report presents clinically relevant advances in the management of non-muscle-invasive bladder cancer, which have been the focus of discussion of expert members of the Spanish Oncology Genitourinary (SOGUG) Multidisciplinary Working Group in the framework of the Genitourinary Alliance project (12GU), designed as a space for the integration of novel information in the care of bladder cancer patients. The present study is focused on different aspects regarding the evaluation of hematuria, assessment of second (or repeated) transurethral resection of bladder cancer, histopathological diagnosis and problems with tumor grading, importance of histological variants, shortage of drug supply, and the current role and influence of immunotherapy and biological markers on the oncological outcome of patients. All proposals and recommendations have a multidisciplinary practical approach and are intended to help clinicians in shared decision making for patients with non-muscle-invasive urothelial cancer. On the basis of the discussion of the current state of research on relevant topics of non-muscle-invasive bladder cancer (NMIBC) among a group of experts of the Spanish Oncology Genitourinary (SOGUG) Working Group, recommendations were proposed to overcome the challenges posed by the management of NMIBC in clinical practice. A unified definition of the term 'microhematuria' and the profile of the patient at risk are needed. Establishing a 'hematuria clinic' would contribute to a centralized and more efficient evaluation of patients with this clinical sign. Second or repeated transurethral resection (re-TUR) needs to be defined, including the time window after the first procedure within which re-TUR should be performed. Complete tumor resection is mandatory when feasible, with specification of the presence or absence of muscle. Budding should be used as a classification system, and stratification of T1 tumors especially in extensive and deep tumors, is advisable. The percentage of the high-grade component should always be reported, and, in multiple tumors, grades should be reported separately. Luminal and basal subtypes can be identified because of possibly different clinical outcomes. Molecular subtypes and immunotherapy are incorporated in the management of muscle-invasive bladder cancer but data on NMIBC are still preliminary.

Context.-Controversies and uncertainty persist in prostate cancer grading. prostate cancer grading. Objective.-To update grading recommendations Data Sources.-Critical review of the literature along with pathology and clinician surveys. Conclusions.-Percent Gleason pattern 4 (%GP4) is as follows: (1) report %GP4 in needle biopsy with Grade Groups (GrGp) 2 and 3, and in needle biopsy on other parts (jars) of lower grade in cases with at least 1 part showing Gleason score (GS) 4 + 4 = 8; and (2) report %GP4: less than 5% or less than 10% and 10% increments thereafter. Tertiary grade patterns are as follows: (1) replace "tertiary grade pattern'' in radical prostatectomy (RP) with "minor tertiary pattern 5 (TP5),'' and only use in RP with GrGp 2 or 3 with less than 5% Gleason pattern 5; and (2) minor TP5 is noted along with the GS, with the GrGp based on the GS. Global score and magnetic resonance imaging (MRI)targeted biopsies are as follows: (1) when multiple undesignated cores are taken from a single MRI-targeted lesion, an overall grade for that lesion is given as if all the involved cores were one long core; and (2) if providing a global score, when different scores are found in the standard and the MRI-targeted biopsy, give a single global score (factoring both the systematic standard and the MRI-targeted positive cores). Grade Groups are as follows: (1) Grade Groups (GrGp) is the terminology adopted by major world organizations; and (2) retain GS 3 + 5 = 8 in GrGp 4. Cribriform carcinoma is as follows: (1) report the presence or absence of cribriform glands in biopsy and RP with Gleason pattern 4 carcinoma. Intraductal carcinoma (IDCP) is as follows: (1) report IDC-P in biopsy and RP; (2) use criteria based on dense cribriform glands (>50% of the gland is composed of epithelium relative to luminal spaces) and/or solid nests and/or marked pleomorphism/necrosis; (3) it is not necessary to perform basal cell immunostains on biopsy and RP to identify IDC-P if the results would not change the overall (highest) GS/GrGp part per case; (4) do not include IDC-P in determining the final GS/GrGp on biopsy and/or RP; and (5) "atypical intraductal proliferation (AIP)'' is preferred for an intraductal proliferation of prostatic secretory cells which shows a greater degree of architectural complexity and/or cytological atypia than typical high-grade prostatic intraepithelial neoplasia, yet falling short of the strict diagnostic threshold for IDC-P. Molecular testing is as follows: (1) Ki67 is not ready for routine clinical use; (2) additional studies of active surveillance cohorts are needed to establish the utility of PTEN in this setting; and (3) dedicated studies of RNA-based assays in active surveillance populations are needed to substantiate the utility of these expensive tests in this setting. Artificial intelligence and novel grading schema are as follows: (1) incorporating reactive stromal grade, percent GP4, minor tertiary GP5, and cribriform/intraductal carcinoma are not ready for adoption in current practice.

In November, 2014, 65 prostate cancer pathology experts, along with 17 clinicians including urologists, radiation oncologists, and medical oncologists from 19 different countries gathered in a consensus conference to update the grading of prostate cancer, last revised in 2005. The major conclusions were: (1) Cribriform glands should be assigned a Gleason pattern 4, regardless of morphology; (2) Glomeruloid glands should be assigned a Gleason pattern 4, regardless of morphology; (3) Grading of mucinous carcinoma of the prostate should be based on its underlying growth pattern rather than grading them all as pattern 4; and (4) Intraductal carcinoma of the prostate without invasive carcinoma should not be assigned a Gleason grade and a comment as to its invariable association with aggressive prostate cancer should be made. Regarding morphologies of Gleason patterns, there was clear consensus on: (1) Gleason pattern 4 includes cribriform, fused, and poorly formed glands; (2) The term hypernephromatoid cancer should not be used; (3) For a diagnosis of Gleason pattern 4, it needs to be seen at 10x lens magnification; (4) Occasional/seemingly poorly formed or fused glands between well-formed glands is insufficient for a diagnosis of pattern 4; (5) In cases with borderline morphology between Gleason pattern 3 and pattern 4 and crush artifacts, the lower grade should be favored; (6) Branched glands are allowed in Gleason pattern 3; (7) Small solid cylinders represent Gleason pattern 5; (8) Solid medium to large nests with rosette-like spaces should be considered to represent Gleason pattern 5; and (9) Presence of unequivocal comedonecrosis, even if focal is indicative of Gleason pattern 5. It was recognized by both pathologists and clinicians that despite the above changes, there were deficiencies with the Gleason system. The Gleason grading system ranges from 2 to 10, yet 6 is the lowest score currently assigned. When patients are told that they have a Gleason score 6 out of 10, it implies that their prognosis is intermediate and contributes to their fear of having a more aggressive cancer. Also, in the literature and for therapeutic purposes, various scores have been incorrectly grouped together with the assumption that they have a similar prognosis. For example, many classification systems consider Gleason score 7 as a single score without distinguishing 3+4 versus 4+3, despite studies showing significantly worse prognosis for the latter. The basis for a new grading system was proposed in 2013 by one of the authors (J.I.E.) based on data from Johns Hopkins Hospital resulting in 5 prognostically distinct Grade Groups. This new system was validated in a multi-institutional study of over 20,000 radical prostatectomy specimens, over 16,000 needle biopsy specimens, and over 5,000 biopsies followed by radiation therapy. There was broad (90%) consensus for the adoption of this new prostate cancer Grading system in the 2014 consensus conference based on: (1) the new classification provided more accurate stratification of tumors than the current system; (2) the classification simplified the number of grading categories from Gleason scores 2 to 10, with even more permutations based on different pattern combinations, to Grade Groups 1 to 5; (3) the lowest grade is 1 not 6 as in Gleason, with the potential to reduce overtreatment of indolent cancer; and (4) the current modified Gleason grading, which forms the basis for the new grade groups, bears little resemblance to the original Gleason system. The new grades would, for the foreseeable future, be used in conjunction with the Gleason system [ie. Gleason score 3+3=6 (Grade Group 1)]. The new grading system and the terminology Grade Groups 1-5 have also been accepted by the World Health Organization for the 2016 edition of Pathology and Genetics: Tumours of the Urinary System and Male Genital Organs.