Second TURB, restaging TURB or repeat TURB in primary T1 non-muscle invasive bladder cancer: impact on prognosis?

PURPOSE: A re-transurethral resection of the bladder (re-TURB) is a well-established approach in managing non-muscle invasive bladder cancer (NMIBC) for various reasons: repeat-TURB is recommended for a macroscopically incomplete initial resection, restaging-TURB is required if the first resection was macroscopically complete but contained no detrusor muscle (DM) and second-TURB is advised for all completely resected T1-tumors with DM in the resection specimen. This study assessed the long-term outcomes after repeat-, second-, and restaging-TURB in T1-NMIBC patients. METHODS: Individual patient data with tumor characteristics of 1660 primary T1-patients (muscle-invasion at re-TURB omitted) diagnosed from 1990 to 2018 in 17 hospitals were analyzed. Time to recurrence, progression, death due to bladder cancer (BC), and all causes (OS) were visualized with cumulative incidence functions and analyzed by log-rank tests and multivariable Cox-regression models stratified by institution. RESULTS: Median follow-up was 45.3 (IQR 22.7-81.1) months. There were no differences in time to recurrence, progression, or OS between patients undergoing restaging (135 patients), second (644 patients), or repeat-TURB (84 patients), nor between patients who did or who did not undergo second or restaging-TURB. However, patients who underwent repeat-TURB had a shorter time to BC death compared to those who had second- or restaging-TURB (multivariable HR 3.58, P = 0.004). CONCLUSION: Prognosis did not significantly differ between patients who underwent restaging- or second-TURB. However, a worse prognosis in terms of death due to bladder cancer was found in patients who underwent repeat-TURB compared to second-TURB and restaging-TURB, highlighting the importance of separately evaluating different indications for re-TURB.

Plasma Androstenedione Concentration Can Discriminate Frail versus Non-Frail Men with Prostate Cancer under Androgen Deprivation Therapy.

BACKGROUND: Androgen deprivation therapy (ADT) is a mainstay of prostate cancer in both adjuvant and palliative settings. Since androgens are crucial for functional status and psychological functions, we evaluated whether blood testosterone, androstenedione, or DHEA concentrations were associated with functional status and psychological alterations in patients with localised (PCa) or metastatic prostate cancer (mPCa) receiving ADT with analogues of luteinising hormone-releasing hormone (LHRH). METHODS: The five Fried criteria were considered to identify frailty syndrome. In addition, complementary evaluations were carried out to measure other variables of interest. Sleep quality was assessed using the Athens Insomnia Scale, cognitive functions were assessed using the Mini-Mental State Examination, and symptoms of depression were measured using the Yesavage Geriatric Depression Scale. Logistic regression analysis was performed to determine if the androgens level could be related to frailty syndrome, sleep impairment, depressive symptoms, and cognitive functions. RESULTS: The results of the multivariate analyses show that high concentrations of androstenedione were significantly associated with frailty syndrome in both groups (p = 0.018; odds ratio = 4.66, 95% confidence interval [1.30-16.6]). There were significant relationships between frailty syndrome and the systemic concentration of androstenedione (p = 0.01), but not the concentration of testosterone (p = 0.60) or DHEA (p = 0.42). In addition, the results of the non-parametric tests show significant results between a decreased gait speed in the two groups (metastatic and localised) and the concentration of androstenedione (p = 0.015). High androstenedione levels were associated with a slow walking speed in the mCaP group (p = 0.016), while high testosterone levels were associated with a better walking speed in the localised CaP group (p = 0.03). For the concentration of androstenedione in plasma, the area under the curve was 0.72, with a 95% CI of 0.55-0.88 with acceptable values, and with a cut-off point of 4.51 pg/mL, a sensitivity of 82.9%, and specificity of 53.8%. No relationships between the concentration of androgens in plasma and sleep quality, cognitive functions, or symptoms of depression suggest that the changes were specific to frailty syndrome. CONCLUSIONS: Further research into the role of androstenedione should be evaluated in follow-up studies in order to recommend its use as a suitable biomarker of frailty syndrome in prostate cancer patients.

Sentinel Lymph Node Biopsy in Prostate Cancer: An Overview of Diagnostic Performance, Oncological Outcomes, Safety, and Feasibility.

Sentinel node biopsy (SNB) for prostate cancer (PCa) represents an innovative technique aimed at improving nodal staging accuracy. The routinary adoption of this procedure in patients undergoing radical prostatectomy (RP) might be crucial to identify candidates who could effectively benefit from extensive pelvic lymph nodal dissection (ePLND). Despite some promising results, SNB for PCa is still considered experimental due to the lack of solid evidence and procedural standardization. In this regard, our narrative review aimed to analyze the most recent literature in this field, providing an overview of both the diagnostic accuracy measures and the oncological outcomes of SNB.

Personalised indocyanine-guided lymphadenectomy for prostate cancer: a randomised clinical trial.

OBJECTIVES: To study the safety and efficacy of a personalised indocyanine-guided pelvic lymph node dissection (PLND) against extended PLND (ePLND) during radical prostatectomy (RP). PATIENTS AND METHODS: Patients who were candidates for RP and lymphadenectomy, with intermediate- or high-risk prostate cancer (PCa) according to the National Comprehensive Cancer Network guidelines, were enrolled in this randomised clinical trial. Randomisation was made 1:1 to indocyanine green (ICG)-PLND (only ICG-stained LNs) or ePLND (obturator fossa, external, internal, and common iliac and presacral LNs). The primary endpoint was the complication rate within 3 months after RP. Secondary endpoints included: rate of major complications (Clavien-Dindo Grade III-IV), time to drainage removal, length of stay, percentage of patients classified as pN1, number of LNs removed, number of metastatic LNs, rate of patients with undetectable prostate-specific antigen (PSA), biochemical recurrence (BCR)-free survival, and rate of patients with androgen-deprivation therapy at 24 months. RESULTS: A total of 108 patients were included with a median follow-up of 16 months. In all, 54 were randomised to ICG-PLND and 54 to ePLND. The postoperative complication rate was higher in the ePLND (70%) vs the ICG-PLND group (32%) (P < 0.001). Differences between major complications in both groups were not statically significant (P = 0.7). The pN1 detection rate was higher in the ICG-PLND group (28%) vs the ePLND group (22%); however, this difference was not statistically significant (P = 0.7). The rate of undetectable PSA at 12 months was 83% in the ICG-PLND vs 76% in the ePLND group, which was not statistically significant. Additionally, there were no statistically significant differences in BCR-free survival between groups at the end of the analysis. CONCLUSIONS: Personalised ICG-guided PLND is a promising technique to stage patients with intermediate- and high-risk PCa properly. It has shown a lower complication rate than ePLND with similar oncological outcomes at short-term follow-up.

Comparison of Frailty Criteria, Cognitive Function, Depressive and Insomnia Symptoms in Men with Localized and Advanced Prostate Cancer under Androgen Deprivation Therapy.

BACKGROUND: Prostate cancer (PCa) is considered one of the most important medical problems in the male population, with a very high incidence after the age of 65. Frailty represents one of the most critical issues facing healthcare due to its inherent relationship with poor healthcare outcomes. The physical phenotype of frailty syndrome based on Fried criteria has been associated with poor outcomes, morbidity, and premature mortality. To date, there are few studies that have analyzed frailty syndrome in patients with localized and advanced (mPCa) disease under androgen-deprivation therapy. OBJECTIVE: Our goal was to assess whether there are differences in frailty criteria between mPCa and localized PCa. We also evaluated the role of other geriatric variables such as depressive and insomnia symptoms, which are frequently reported in cancer patients. METHODS: In this cross-sectional study, frailty syndrome was evaluated in both groups, as well as its possible relationship with cognitive functions, depressive and insomnia symptoms, and other clinical variables related to PCa and its treatment. Frailty was defined on Fried's criteria: low lean mass, weakness, self-reported exhaustion, low activity level, and slow walking speed; prefrailty was defined as having one or two of those criteria and frailty as having three or more, depressive symptoms were defined by the Yesavage scale, cognitive functions with the Mini-Mental examination test, and insomnia symptoms by the Athens scale and self-reported health status. RESULTS: The prevalence of prefrailty/frailty was slightly higher in mPCa compared to localized PCa (81.5% versus 72.3%, respectively), however by analyzing each of the frailty criteria, two of them were significantly reduced in mPCa compared to localized PCa patients, e.g., gait speed (p = 0.001) and muscle strength (p = 0.04). The reduced gait speed and muscle strength in mPCa were not due to the increased age in mPCa group, or to an increase in comorbidities or shorter time under androgen-deprivation therapy. The symptoms of insomnia were significantly higher in mPCa patients compared to those with localized PCa (p < 0.05) whereas cognitive functions or depressive symptoms were not significantly different between the two groups. CONCLUSION: Patients with mPCa under androgen-deprivation therapy display higher alterations in gait speed and muscular strength and insomnia symptoms, thus interventions should be aimed to reduce these alterations in order to limit adverse outcomes related to them and to improve quality of life in these patients.

Impact of concurrent tumour events on the prostate cancer outcomes of germline BRCA2 mutation carriers.

BACKGROUND: Several studies have reported the association of germline BRCA2 (gBRCA2) mutations with poor clinical outcomes in prostate cancer (PCa), but the impact of concurrent somatic events on gBRCA2 carriers survival and disease progression is unknown. PATIENTS AND METHODS: To ascertain the role of frequent somatic genomic alterations and histology subtypes in the outcomes of gBRCA2 mutation carriers and non-carriers, we correlated the tumour characteristics and clinical outcomes of 73 gBRCA2 and 127 non-carriers. Fluorescent in-situ hybridisation and next-generation sequencing were used to detect copy number variations in BRCA2, RB1, MYC and PTEN. Presence of intraductal and cribriform subtypes was also assessed. The independent impact of these events on cause-specific survival (CSS), metastasis-free survival and time to castration-resistant disease was assessed using cox-regression models. RESULTS: Somatic BRCA2-RB1 co-deletion (41% versus 12%, p < 0.001) and MYC amplification (53.4% versus 18.8%, p < 0.001) were enriched in gBRCA2 compared to sporadic tumours. Median CSS from diagnosis of PCa was 9.1 versus 17.6 years in gBRCA2 carriers and non-carriers, respectively (HR 2.12; p = 0.002), Median CSS in gBRCA2 carriers increased to 11.3 and 13.4 years in the absence of BRCA2-RB1 deletion or MYC amplification, respectively. Median CSS of non-carriers decreased to 8 and 2.6 years if BRCA2-RB1 deletion or MYC amplification were detected. CONCLUSIONS: gBRCA2-related prostate tumours are enriched for aggressive genomic features, such as BRCA2-RB1 co-deletion and MYC amplification. The presence or absence of these events modify the outcomes of gBRCA2 carriers.

Epidemiology, Diagnosis and Management of Penile Cancer: Results from the Spanish National Registry of Penile Cancer.

INTRODUCTION: Penile cancer (PC) is a rare malignancy with an overall incidence in Europe of 1/100,000 males/year. In Europe, few studies report the epidemiology, risk factors, clinical presentation, and treatment of PC. The aim of this study is to present an updated outlook on the aforementioned factors of PC in Spain. MATERIALS AND METHODS: A multicentric, retrospective, observational epidemiological study was designed, and patients with a new diagnosis of PC in 2015 were included. Patients were anonymously identified from the Register of Specialized Care Activity of the Ministry of Health of Spain. All Spanish hospitals recruiting patients in 2015 were invited to participate in the present study. We have followed a descriptive narration of the observed data. Continuous and categorical data were reported by median (p25th-p75th range) and absolute and relative frequencies, respectively. The incidence map shows differences between Spanish regions. RESULTS: The incidence of PC in Spain in 2015 was 2.55/100,000 males per year. A total of 586 patients were identified, and 228 patients from 61 hospitals were included in the analysis. A total of 54/61 (88.5%) centers reported ≤ 5 new cases. The patients accessed the urologist for visually-assessed penile lesions (60.5%), mainly localized in the glans (63.6%). Local hygiene, smoking habits, sexual habits, HPV exposure, and history of penile lesions were reported in 48.2%, 59.6%, 25%, 13.2%, and 69.7%. HPV-positive lesions were 18.1% (28.6% HPV-16). The majority of PC was squamous carcinoma (95.2%). PC was ≥cT2 in 45.2% (103/228) cases. At final pathology, PC was ≥pT2 in 51% of patients and ≥pN1 in 17% of cases. The most common local treatment was partial penectomy (46.9% cases). A total of 47/55 (85.5%) inguinal lymphadenectomies were open. Patients with ≥pN1 disease were treated with chemotherapy in 12/39 (40.8%) of cases. CONCLUSIONS: PC incidence is relatively high in Spain compared to other European countries. The risk factors for PC are usually misreported. The diagnosis and management of PC are suboptimal, encouraging the identification of referral centers for PC management.

Prognosis of Primary Papillary Ta Grade 3 Bladder Cancer in the Non-muscle-invasive Spectrum.

BACKGROUND: Ta grade 3 (G3) non-muscle-invasive bladder cancer (NMIBC) is a relatively rare diagnosis with an ambiguous character owing to the presence of an aggressive G3 component together with the lower malignant potential of the Ta component. The European Association of Urology (EAU) NMIBC guidelines recently changed the risk stratification for Ta G3 from high risk to intermediate, high, or very high risk. However, prognostic studies on Ta G3 carcinomas are limited and inconclusive. OBJECTIVE: To evaluate the prognostic value of categorizing Ta G3 compared to Ta G2 and T1 G3 carcinomas. DESIGN, SETTING, AND PARTICIPANTS: Individual patient data for 5170 primary Ta-T1 bladder tumors from 17 hospitals were analyzed. Transurethral resection of the tumor was performed between 1990 and 2018. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Time to recurrence and time to progression were analyzed using cumulative incidence functions, log-rank tests, and multivariable Cox-regression models with interaction terms stratified by institution. RESULTS AND LIMITATIONS: Ta G3 represented 7.5% (387/5170) of Ta-T1 carcinomas of which 42% were classified as intermediate risk. Time to recurrence did not differ between Ta G3 and Ta G2 (p = 0.9) or T1 G3 (p = 0.4). Progression at 5 yr occurred for 3.6% (95% confidence interval [CI] 2.7-4.8%) of Ta G2, 13% (95% CI 9.3-17%) of Ta G3, and 20% (95% CI 17-23%) of T1 G3 carcinomas. Time to progression for Ta G3 was shorter than for Ta G2 (p < 0.001) and longer than for T1 G3 (p = 0.002). Patients with Ta G3 NMIBC with concomitant carcinoma in situ (CIS) had worse prognosis and a similar time to progression as for patients with T1 G3 NMIBC with CIS (p = 0.5). Multivariable analyses for recurrence and progression showed similar results. CONCLUSIONS: The prognosis of Ta G3 tumors in terms of progression appears to be in between that of Ta G2 and T1 G3. However, patients with Ta G3 NMIBC with concomitant CIS have worse prognosis that is comparable to that of T1 G3 with CIS. Our results support the recent EAU NMIBC guideline changes for more refined risk stratification of Ta G3 tumors because many of these patients have better prognosis than previously thought. PATIENT SUMMARY: We used data from 17 centers in Europe and Canada to assess the prognosis for patients with stage Ta grade 3 (G3) non-muscle-invasive bladder cancer (NMIBC). Time to cancer progression for Ta G3 cancer differed from both Ta G2 and T1 G3 tumors. Our results support the recent change in the European Association of Urology guidelines for more refined risk stratification of Ta G3 NMIBC because many patients with this tumor have better prognosis than previously thought.

Management of renal cell carcinoma in transplant kidney: a systematic review and meta-analysis.

INTRODUCTION: After transplantation, approximately 10% of renal cell carcinomas are detected in graft kidneys. These tumors (gRCC) present surgeons with the difficulty of finding a treatment that guarantees both oncological clearance and maintenance of function. We conducted a systematic review and an individual patient data meta-analysis on the oncology, safety and functional outcomes of the available treatments for gRCC. EVIDENCE ACQUISITION: A systematic search was performed across MEDLINE, EMBASE, and Web of Science including any study reporting perioperative, functional and survival outcomes for patients undergoing graft nephrectomy (GN), partial nephrectomy (PN) or thermal ablation (TA) for gRCC. Quade's ANCOVA, Spearman Rho and Pearson χ2, Kaplan-Meier, Log-rank and Standard Cox regression and other tests were used to compare treatments. Studies' quality was evaluated using a modified version of Newcastle Ottawa Scale. EVIDENCE SYNTHESIS: A number of 29 studies (357 patients) were included. No differences between TA and PN were found in terms of safety, functional and oncological outcomes for T1a gRCCs. When applied to pT1b gRCC, PN showed no difference in complications, progression or cancer-specific deaths compared to smaller lesions; PN validity for pT2 gRCCs should be considered unverified due to lack of sufficient evidence. The efficacy and safety of PN or TA for multiple gRCC remain controversial. In case of non-functioning, large (T≥2), complicated or metastatic gRCCs, GN appears to be the most reasonable choice. Quality of evidence ranged from very low to moderate. Studies with large cohorts and longer follow-up are still needed to clarify oncological and functional differences. CONCLUSIONS: PN and TA might be offered as a nephron-sparing treatment in patients with T1a gRCC. There is no significant difference between these options and GN in terms of oncological outcomes and complications. PN and TA offer similar functional outcomes and graft preservation. PN for T1b gRCC seems feasible and safe, but its validity should be considered unverified.

Long-term results with custom-linked iodine-125 seeds and real-time brachytherapy in low- and intermediate-risk prostate cancer.

Purpose: Brachytherapy (BT) with iodine-125 (125I) seeds is effective in low- and intermediate-risk prostate carcinoma, with fewer side effects compared to other techniques, but relapses increase in long-term. In the present paper, 10-year biochemical relapse-free survival (BRFS) results are presented. Material and methods: Between 2007 and 2016, 706 patients were treated with real-time technique using Bard-ProLink™ system. 145 Gy was administered to the prostate with exclusive BT and 108 Gy after 46 Gy of external radiotherapy (EBRT). Androgen deprivation therapy was applied in 19.3% of patients. Results: Median follow-up was 96 months (range, 24-163 months). BRFS at 5 and 10 years was 95% and 91.1%, respectively. For 480 low-risk cases, BRFS at 5 and 10 years was 95.7% and 92.7%, and for 226 intermediate-risk cases, it was 92.7% and 88%, respectively (p < 0.05). With combined treatment of EBRT + BT, 133 cases (59%) of intermediate-risk were treated without differences with exclusive BT. Gleason score 4 + 3 cases dropped to 72.8% at 10 years (p < 0.001), with androgen deprivation therapy (ADT) to 90.9% and without ADT to 66.8%; it was worse if patients had exclusive BT. 10-year BRFS for T1c was 95% compared to 84% for T2 (p < 0.001). Initial prostate specific antigen (PSA) > or < 10 showed no differences. With > 50% biopsy cores positive, it fell to 80% at 10 years (p < 0.001). In 154 patients up to 60 years of age, 10-year BRFS was 97.6%. Urinary complications appeared in 16.9% of cases in exclusive BT vs. 26.1% in EBRT + BT. Grade 2+ urinary late complications were observed in 19.1% and grade 3+ in 5.8% of patients. Rectal toxicity was 4% (2.5% in BT alone and 10.1% in RT + BT), while G3+ was seen in 0.1%. Conclusions: Real-time BT with custom-linked 125I seeds is a very effective long-term treatment in low- and intermediate-risk prostate carcinoma. With Gleason score 4 + 3 or > 50% biopsy cores positive, we recommend combined treatment with additional ADT for 6 months.

Free-indocyanine green-guided pelvic lymph node dissection during radical prostatectomy.

INTRODUCTION AND OBJECTIVES: Extended Pelvic Lymph Node Dissection (ePLND) remains the most accurate technique for the detection of occult lymph node metastases (LNMs) in prostate cancer (CaP) patients. Here we aim to examine whether free-Indocyanine Green (F-ICG) could accurately assess the pathological nodal (pN) status in CaP patients during real-time lymphangiography as a potential replacement for ePLND. MATERIALS AND METHODS: 219 consecutive patients undergoing F-ICG-guided PLND, ePLND and radical prostatectomy (RP) for clinical-localized CaPwere included in this prospective single-center study. The pathological outcomes of F-ICG-guided PLND were compared to confirmatory ePLND. Parameters of a binary diagnostic test for the proper classification of the pN status of patients ('per-patient' analysis) and for the probability of detecting all the metastatic LNs ('per-node' analysis) were calculated. Outcome measures were prevalence, accuracy (Acc), sensitivity (Se), negative predictive value (NPV), and likelihood ratio of a negative F-ICG-guided PLND test result [LR(-)]. RESULTS: F-ICG-guided PLND successfully visualized LNs in all procedures with no adverse events. The overall per-patient F-ICG staging Acc was 97.7%, Se was 91.4%, with a NPV of 97.0%, and LR(-) of 8.6%. At the overall per-node level, 4,780 LNs were removed and 1,535 (32.1%) were fluorescent in vivo. F-ICG-guided PLND identified LNMs with a Se of 63.4%. CONCLUSIONS: This study confirms that F-ICG-guided lymphangiography correctly staged almost 98% of patients. The high per-patient NPV suggested that avoiding ePLND is safe for most patients when F-ICG stained nodes were pN0. Thus, more conservative approaches might minimise perioperative morbidity during LNMs diagnosis in selected patients.

Bilateral Seminal Vesicle Invasion Is Not Associated with Worse Outcomes in Locally Advanced Prostate Carcinoma.

Background and Objectives: Patients with seminal vesicle invasion (SVI) are a highly heterogeneous group. Prognosis can be affected by many clinical and pathological characteristics. Our aim was to study whether bilateral SVI (bi-SVI) is associated with worse oncological outcomes. Materials and Methods: This is an observational retrospective study that included 146 pT3b patients treated with radical prostatectomy (RP). We compared the results between unilateral SVI (uni-SVI) and bi-SVI. The log-rank test and Kaplan-Meier curves were used to compare biochemical recurrence-free survival (BCR), metastasis-free survival (MFS), and additional treatment-free survival. Cox proportional hazard models were used to identify predictors of BCR-free survival, MFS, and additional treatment-free survival. Results: 34.93% of patients had bi-SVI. The median follow-up was 46.84 months. No significant differences were seen between the uni-SVI and bi-SVI groups. BCR-free survival at 5 years was 33.31% and 25.65% (p = 0.44) for uni-SVI and bi-SVI. MFS at 5 years was 86.03% vs. 75.63% (p = 0.1), and additional treatment-free survival was 36.85% vs. 21.93% (p = 0.09), respectively. In the multivariate analysis, PSA was related to the development of BCR [HR 1.34 (95%CI: 1.01-1.77); p = 0.03] and metastasis [HR 1.83 (95%CI: 1.13-2.98); p = 0.02]. BCR was also influenced by lymph node infiltration [HR 2.74 (95%CI: 1.41-5.32); p = 0.003]. Additional treatment was performed more frequently in patients with positive margins [HR: 3.50 (95%CI: 1.65-7.44); p = 0.001]. Conclusions: SVI invasion is an adverse pathology feature, with a widely variable prognosis. In our study, bilateral seminal vesicle invasion did not predict worse outcomes in pT3b patients despite being associated with more undifferentiated tumors.

Plasma Nickel Levels Correlate with Low Muscular Strength and Renal Function Parameters in Patients with Prostate Cancer.

Nickel is associated with cancer in occupational exposure. However, few studies have been devoted to analyzing the effects of nickel at environmental concentrations in cancer patients. In this work, the concentration of nickel in blood samples from patients with prostate cancer (PCa) was evaluated because this metal displays androgenic and estrogenic effects that play a crucial role in prostate carcinogenesis and treatment. We, therefore, compared blood nickel concentration in patients with PCa (non-occupationally exposed) (n = 46) with those in control age-matched individuals (n = 46). We also analyzed if there was any association between sociodemographic factors, clinical variables, geriatric evaluation assessment results, blood cell counts, or biochemical, androgen and estrogen concentrations. Using inductively coupled plasma-mass spectroscopy on the plasma samples, we observed a mean nickel level of 4.97 ± 1.20 µg/L in the PCa group and 3.59 ± 0.49 µg/L in the control group, with a non-significant effect (p = 0.293) between the two groups. The nickel concentration was significantly correlated with patient age (p = 0.005) and reduced handgrip strength (p = 0.003). Regarding biochemical parameters, significant associations were found with the renal glomerular filtration rate (p = 0.024) and blood urea levels (p = 0.016). No significant correlations were observed with other blood analytical parameters or testosterone or estradiol levels. These specific renal function and muscle strength effects were observed at environmental nickel exposure levels believed to be safe or at least far from the high concentrations observed after occupational exposure. Therefore, these parameters deserve further study, given that they could help pinpoint further public health concerns regarding nickel exposure in the general population.

Adverse Pathological Findings at Radical Prostatectomy following Active Surveillance: Results from the Movember GAP3 Cohort.

Background: Little is known about the consequences of delaying radical prostatectomy (RP) after Active Surveillance (AS) according to stringent or wider entry criteria. We investigated the association between inclusion criteria and rates, and timing of adverse pathological findings (APFs) among patients in GAP3 cohorts. Methods: APFs (GG ≥ 3, pT ≥ 3, pN > 0 and positive surgical margins [R1]) were accounted for in very low-risk (VLR: grade group [GG] 1, cT1, positive cores < 3, PSA < 10 ng/mL, PSA density [PSAD] < 0.15 ng/mL/cm3) and low-risk (LR: GG1, cT1-2, PSA ≤ 10 ng/mL) patients undergoing subsequent RP. The Kaplan−Meier method and log−rank test analyzed APF-free survival. Stratified mixed effects models analyzed association. Results: Out of 21,169 patients on AS, 1742 (VLR: 721; LR: 1021) underwent delayed RP. Most (60.8%) did not have APFs. APFs occurred more frequently (44.6% vs. 31.7%; OR 1.54, p < 0.001) and earlier (median time: 40.3 vs. 62.6 months; p < 0.001) in LR patients, and consisted of pT ≥ 3 (OR 1.47, p = 0.013) or R1 (OR 1.80, p < 0.001), but not of GG ≥ 3 or node involvement. Age (OR 1.05, p < 0.001), PSAD (OR 23.21, p = 0.003), and number of positive cores (OR 1.16, p = 0.004) were independently associated with APFs. Conclusions: AS stands as a safe option for low-risk patients, and most do not have APFs at surgery. Wider entry criteria are associated with pT3 and R1. The prognostic implications remain uncertain.

Active Surveillance for Men Younger than 60 Years or with Intermediate-risk Localized Prostate Cancer. Descriptive Analyses of Clinical Practice in the Movember GAP3 Initiative.

Background: Active surveillance (AS) is a management option for men diagnosed with low-risk prostate cancer. Opinions differ on whether it is safe to include young men (≤60 yr) or men with intermediate-risk disease. Objective: To assess whether reasons for discontinuation, treatment choice after AS, and adverse pathology at radical prostatectomy (RP; N1, or ≥GG3, or ≥pT3) differ for men ≤60 yr or those with European Association of Urology (EAU) intermediate-risk disease from those for men >60 yr or those with EAU low-risk disease. Design setting and participants: We analyzed data from 5411 men ≤60 yr and 14 959 men >60 yr, 14 064 men with low-risk cancer, and 2441 men with intermediate-risk cancer, originating from the GAP3 database (21 169 patients/27 cohorts worldwide). Outcome measurements and statistical analysis: Cumulative incidence curves were used to estimate the rates of AS discontinuation and treatment choice. Results and limitations: The probability of discontinuation of AS due to disease progression at 5 yr was similar for men aged ≤60 yr (22%) and those >60 yr (25%), as well as those of any age with low-risk disease (24%) versus those with intermediate-risk disease (24%). Men with intermediate-risk disease are more prone to discontinue AS without evidence of progression than men with low-risk disease (at 1/5 yr: 5.9%/14.2% vs 2.0%/8.8%). Adverse pathology at RP was observed in 32% of men ≤60 yr compared with 36% of men >60 yr (p = 0.029), and in 34% with low-risk disease compared with 40% with intermediate-risk disease (p = 0.048). Conclusions: Our descriptive analysis of AS practices worldwide showed that the risk of progression during AS is similar across the age and risk groups studied. The proportion of adverse pathology was higher among men >60 yr than among men ≤60 yr. These results suggest that men ≤60 yr and those with EAU intermediate-risk disease should not be excluded from opting for AS as initial management. Patient summary: Data from 27 international centers reflecting daily clinical practice suggest that younger men or men with intermediate-risk prostate cancer do not hold greater risk for disease progression during active surveillance.

T1G1 Bladder Cancer: Prognosis for this Rare Pathological Diagnosis Within the Non-muscle-invasive Bladder Cancer Spectrum.

BACKGROUND: The pathological existence and clinical consequence of stage T1 grade 1 (T1G1) bladder cancer are the subject of debate. Even though the diagnosis of T1G1 is controversial, several reports have consistently found a prevalence of 2-6% G1 in their T1 series. However, it remains unclear if T1G1 carcinomas have added value as a separate category to predict prognosis within the non-muscle-invasive bladder cancer (NMIBC) spectrum. OBJECTIVE: To evaluate the prognostic value of T1G1 carcinomas compared to TaG1 and T1G2 carcinomas within the NMIBC spectrum. DESIGN, SETTING, AND PARTICIPANTS: Individual patient data for 5170 primary Ta and T1 bladder tumors from 17 hospitals in Europe and Canada were analyzed. Transurethral resection (TUR) was performed between 1990 and 2018. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Time to recurrence and progression were analyzed using cumulative incidence functions, log-rank tests, and multivariable Cox regression models stratified by institution. RESULTS AND LIMITATIONS: T1G1 represented 1.9% (99/5170) of all carcinomas and 5.3% (99/1859) of T1 carcinomas. According to primary TUR dates, the proportion of T1G1 varied between 0.9% and 3.5% per year, with similar percentages in the early and later calendar years. We found no difference in time to recurrence between T1G1 and TaG1 (p = 0.91) or between T1G1 and T1G2 (p = 0.30). Time to progression significantly differed between TaG1 and T1G1 (p < 0.001) but not between T1G1 and T1G2 (p = 0.30). Multivariable analyses for recurrence and progression showed similar results. CONCLUSIONS: The relative prevalence of T1G1 diagnosis was low and remained constant over the past three decades. Time to recurrence of T1G1 NMIBC was comparable to that for other stage/grade NMIBC combinations. Time to progression of T1G1 NMIBC was comparable to that for T1G2 but not for TaG1, suggesting that treatment and surveillance of T1G1 carcinomas should be more like the approaches for T1G2 NMIBC in accordance with the intermediate and/or high risk categories of the European Association of Urology NMIBC guidelines. PATIENT SUMMARY: Although rare, stage T1 grade 1 (T1G1) bladder cancer is still diagnosed in daily clinical practice. Using individual patient data from 17 centers in Europe and Canada, we found that time to progression of T1G1 cancer was comparable to that for T1G2 but not TaG1 cancer. Therefore, our results suggest that primary T1G1 bladder cancers should be managed with more aggressive treatment and more frequent follow-up than for low-risk bladder cancer.

[Tumor markers in urological cancers: an update.] / Actualización en biomarcadores tumorales en urología.

La investigación en biomarcadores tumorales estásujeta a unas estrictas normas para su comercialización.Pese a ello, en su uso abierto a distintas poblaciones,somos sometidos a una presión comercialque en ocasiones puede derivar inconscientemente aextender su uso a objetivos para los que no han sidoestrictamente testados...

La investigación en biomarcadores tumorales estásujeta a unas estrictas normas para su comercialización.Pese a ello, en su uso abierto a distintas poblaciones,somos sometidos a una presión comercialque en ocasiones puede derivar inconscientemente aextender su uso a objetivos para los que no han sidoestrictamente testados...

Urinary biomarkers for the optimization of bladder cancer screening. / Optimización del despistaje de cáncer de urotelio con biomarcadores.

Bladder cancer (BCa) represents the 7thmost frequent cancer in the male population worldwideand the 10th when both genders are considered.Due its high prevalence, result of high incidence andlow cancer specific mortality in low grade disease, BCarepresents a significant clinical and financial burden.Despite our knowledge of the natural history of thedisease and of the risk factors associated with BCa(age, gender, smoking history and certain chemicals)and, the evidence that outcomes, related directly tothe stage of the disease, are affected by delays in thediagnosis, "screening" is not even considered by mosturological societies and relevant international urologicalguidelines.The aim of the present article is to provide the readerwith an up to date, non-systematic, narrative reviewof the most relevant articles focussed on the useof urinary biomarkers (UBMs) in the screening of BCaboth, mass and high risk population screening, theeconomic assessment of the cost-effectiveness of suchprogrammes, as well as, potential innovations for thefuture of BCa screening.

El cáncer de vejiga (CV) representa el 7ºcáncer más frecuente en varones a nivel mundial y el10º cuando se consideran ambos sexos. Debido a sualta prevalencia, resultado de la alta incidencia y bajamortalidad cáncer específica en la enfermedad debajo grado, el CV representa un problema importanteen términos tanto clínicos como económicos.A pesar de nuestro conocimiento de la historia naturalde la enfermedad y de los factores de riesgo asociadoscon el CV (edad, género, tabaquismo y ciertosquímicos) y la evidencia de que los resultados, relacionadosdirectamente con el estadio de la enfermedad,se ven afectados por retrasos en el diagnóstico, el cribadoo despistaje (screening) ni siquiera es consideradopor la mayoría de las sociedades urológicas ni porlas guías urológicas internacionales.El objetivo del presente artículo es proporcionar allector una revisión narrativa actualizada, no sistemática,de los artículos más relevantes, centrados en eluso de biomarcadores urinarios (BMUs) en el cribadodel CV, tanto en el cribado masivo como en el de poblaciónde alto riesgo, su evaluación en términos decoste-eficiencia, así como posibles innovaciones parael futuro del cribado del CV.

Optimization of the different therapeutic strategies in muscle invasive bladder cancer using biomarkers. / Optimización de las diferentes estrategias terapéuticas en tumor vesical infi ltrante usando biomarcadores.

Predicting response to definitive treatmentsis a fascinating challenge which develops throughthe evolution of a panel of convincing molecularbiomarkers capable of adding in clinical decissionsdespite interpatient and intratumoral heterogenicity.Muscle-invasive bladder cancer (MIBC) can be locallytreated either with radical cystectomy (RC) with or withoutneoadyuvant chemotherapy or bladder preservationapproaches such as trimodal therapy (TMT) includingmaximal transurethral resection of bladder tumor(TURBt) followed by external beam radiotherapy withconcurrent systemic radio-sensitizing chemotherapy.Conventional or novel/targeted systemic agents areessential parts of perioperative multidisciplinary managementconsidering both neoadjuvant and adjuvantsetting. Advances in molecular biology such as next generation sequencing and whole genome or transcriptomicanalysis, provided novel insights to achieve a fullunderstanding of the biology behind MIBC helping toidentify emerging predictive signatures. Although severalprogresses have been made, real-world applicationof molecular biomarkers in MIBC scenario is hinderedby lack of standardization, and low reproducibility. Inthis review we aim to present the emerging role of novelmolecular biomarkers in predicting response to localtreatments and systemic agents in MIBC.

La predicción de respuesta a tratamientosdefinitivos en un tumor es un desafío fascinantemediada por un panel de biomarcadores quepuedieran aportar información para tomar decisionesterapéuticas, pese a la heterogenicidad entrepacientes e intratumoral. El tumor vesical infiltrante(TVI) puede tratarse con cistectomía radical (CR) cono sin neoadyuvancia (NAD) o estrategias de preservaciónvesical como la terapia trimodal (TMT), que incluyeresección transuretral (RTU) máxima seguidade radioterapia externa con una quimioterapia radiosensibilizadoraconcomitante. Las terapias convencionaleso dirigidas son esenciales dentro del manejomultidisciplinar necesario en sus facetas neo y adyuvantes.Los avances en biología molecular, como lasecuenciación moderna y el análisis transcriptómicodel genoma, han permitido empezar a entenderel comportamiento molecular del TVI ayudando aidentificar firmas predictivas. Aunque se han hechoprogresos, la aplicación asistencial de biomarcadores en TVI está frenada por la falta de estandarización yla baja reproducibilidad de distintos resultados esperanzadores.En esta revisión, pretendemos exponerel papel emergente de nuevos marcadores molecularesen la predicción de respuesta a tratamientos localesy sistémicos en el TVI.