Intraprostatic hormone dosage: Validation of a novel prostate biopsy technique.

BACKGROUND: Advances in chromatography and mass spectrometry have allowed us to develop a novel technique for measuring intraprostatic hormone concentrations directly on prostate needle biopsies, rather than using traditional punch excision. This has significant clinical implications as intraprostatic dihydrotestosterone and testosterone levels could help monitor prostate growth, neoplasia and castration resistance. METHODS: Patients undergoing radical cystoprostatectomy for bladder cancer were prospectively included. Each prostate specimen received one 90mg punch excision and six needle biopsies. Intraprostatic hormones were dosed through gas chromatography-mass spectrometry. RESULTS: We included twenty patients, of which eleven were incidentally diagnosed with prostate cancer; four had ISUP 1 (20%) and seven had ISUP 2 (35%). The prostate biopsy technique was unable to obtain measures for testosterone, Delta-4-androsterone and androstenedione. Tissue concentrations of DHEA, DHT, E1 and E2 can be obtained with no significant difference from the reference established on a punch from a single biopsy core sample. CONCLUSIONS: Our study demonstrates that intraprostatic concentrations of DHEA, DHT, E1 and E2 can be measured without significant difference from the reference established on a single punch excision. This finding opens the way to research on the interactions between endocrinology and prostate oncogenesis and particularly on the mechanisms of resistance to hormone therapies in vivo.

Relationship of preoperative androgen levels and metabolic syndrome with quality of life and erectile function in patients who are to undergo radical prostatectomy.

This study aims to investigate whether clinical and biological preoperative characteristics of patients who were to undergo radical prostatectomy were associated with impairment in patient-reported quality of life (QoL) and erectile dysfunction immediately before intervention. We evaluated patient-reported outcomes among 1019 patients (out of 1343) of the AndroCan study, willing to score the Aging Male Symptom (AMS) and the International Index of Erectile Function 5-item (IIEF-5) auto-questionnaires. Univariate linear regression and robust multiple regression were used to ascertain the relationship between demographic, clinical, and hormonal parameters and global AMS or IIEF-5 scores. As a result, most patients (85.1') of the Androcan cohort agreed to complete questionnaires. Significantly higher IIEF-5 global scores were found in non-Caucasian and obese patients, with larger waist circumference, metabolic syndrome, diabetes mellitus, cardiovascular disease, hypertension, high blood sugar, concomitant medications, and hypogonadism, while the AMS global score was significantly higher in patients with larger waist circumference, metabolic syndrome, high blood pressure, raised glycemia, and concomitant medication. The IIEF-5 global score was correlated to age, dehydroepiandrosterone (DHEA), fat mass percentage, and androstenediol (D5). The AMS global score was significantly correlated to DHEA, D5, and DHEA sulfate. Finally, the multivariate models showed that QoL and erectile function were significantly affected, before surgery, by symptoms and signs that are usually considered as pertaining to the metabolic syndrome, while sexual hormones are essentially correlated to erectile dysfunction.

PSA and obesity among men with localized prostate cancer: results of the ANDROCAN study.

PURPOSE: PSA is known to be lowered in obese patients. There is a lack of data regarding patients with prostate cancer. Our objective was to prospectively assess the relationship PSA concentration, PSA mass and BMI in a cohort of patients with localized prostate cancer. METHODS: A prospective, multicenter cohort study was conducted including patients undergoing radical prostatectomy. Clinical and biological data were collected for each patient before surgery. RESULTS: A total of 1343 patients were analyzed. Mean age was 64.0 years. Mean weight was 82.2 kg and mean BMI was 26.8 kg/m2. Mean PSA concentration was 8.7 ng/mL and mean PSA mass 29.3 ng. On univariate analysis, an association was found between PSA mass and either BMI, weight and waist circumference. No association was found between PSA concentration and each weight parameters. On multivariate analysis, obesity was not an independent predictor of PSA concentration (p = 0.73). Independent predictors of PSA concentration were cardiovascular disease (negative association, p = 0.034), predominant Gleason 4 (positive association, p < 0.001) and pT3a (positive association, p < 0.001). BMI was an independent predictor of PSA mass (positive association, p = 0.009). PSA mass was negatively associated with TT (p = 0.015) and cardiovascular disease (p = 0.003), and positively associated with BT (p = 0.032), Gleason grade ≥ 4 + 3 (p < 0.001) and pT3a (p < 0.001). CONCLUSION: In this prospective study of patients with localized prostate cancer, higher BMI was associated with higher PSA mass but not with higher PSA concentration. Screening obese patients with a specific PSA method does not appear to be critical.

Metabolic syndrome, levels of androgens, and changes of erectile dysfunction and quality of life impairment 1 year after radical prostatectomy.

Robust data evaluating the association of preoperative parameters of the patients with quality of life after radical prostatectomy are lacking. We investigated whether clinical and biological preoperative characteristics of the patients were associated with impaired patient-reported quality of life (QoL) and sexual outcomes 1 year after radical prostatectomy. We evaluated patient-reported outcomes among the 1343 men participating in the AndroCan trial (NCT02235142). QoL and erectile dysfunction (ED) were assessed before and 1 year after radical prostatectomy using validated self-assessment questionnaires (Aging Male's Symptoms [AMS] and the 5-item abridged version of the International Index of Erectile Function [IIEF5]). At baseline, 1194 patients (88.9%) accepted to participate. A total of 750 (55.8%) patients answered the 1-year postoperative questionnaires. Out of them, only 378 (50.4% of responders) provided answers that could be used for calculations. One year after prostatectomy, ED had worsened by 8.0 (95% confidence interval [CI]: 7.3-8.7; P < 0.0001) out of a maximum of 20. The global AMS score has worsened by 2.8 (95% CI: 1.7-3.8; P < 0.0001). ED scores 1 year postsurgery were positively correlated with preoperative age and percentage of fat mass, and negatively correlated with total cholesterol, dehydroepiandrosterone (DHEA), and androstenediol (D5); AMS were poorly correlated with preoperative parameters. QoL and sexual symptoms significantly worsened after radical prostatectomy. Baseline bioavailable testosterone levels were significantly correlated with smaller changes on AMS somatic subscores postprostatectomy. These findings may be used to inform patients with newly diagnosed prostate cancer.

Measured glomerular filtration rate (GFR) significantly and rapidly decreases after radical cystectomy for bladder cancer.

Precise determination of glomerular filtration rate (GFR) is essential for the management of patients with muscle-invasive bladder cancer (MIBC). We aim to describe the early evolution of measured GFR (mGFR) after radical cystectomy and urinary diversion (RCUD) and to identify risk factors for GFR decline. GFR measurement using 51Cr-EDTA continuous infusion, estimated GFR (eGFR) from five published equations and renal scintigraphy with split renal function determination were performed before and 6 months after RCUD. Chronic Kidney Disease (mGFR < 60 mL/min/1.73 m2) and GFR stages were defined according to the KDIGO guidelines using mGFR. Twenty-seven patients (men 85%, median age 65, IQR 59; 68 years) were included. A total of 20 (74%) patients experienced significant mGFR decline at 6 months postoperatively. Median mGFR decreased from 84.1 pre-operatively (IQR 65.3; 97.2) to 69.9 mL/min/1.73 m2 (IQR 55.0; 77.9) 6 months after surgery (p < 0.001). Thirteen (48%) patients had a progression to a worse GFR stage. Of the 22 patients without pre-operative CKD, 5 (23%) developed post-operative CKD. Diabetes mellitus was more frequent in patients in the highest tertile of relative mGFR decline (44% vs. 11%, p = 0.02) and platinum-based adjuvant chemotherapy tended to be more frequently used in these patients (44% vs. 17%, p = 0.06). Importantly, pre-operative weight was independently and negatively associated with post-operative mGFR and with mGFR slope in multivariable analyses. In this prospective series, we demonstrated that early and significant mGFR decline occurred after RCUD and perioperative platinum-based chemotherapy, especially in patients with diabetes mellitus and overweight.

Aggressiveness of Localized Prostate Cancer: the Key Value of Testosterone Deficiency Evaluated by Both Total and Bioavailable Testosterone: AndroCan Study Results.

Failure rates after first-line treatment of localized prostate cancer (PCa) treatment remain high. Improvements to patient selection and identification of at-risk patients are central to reducing mortality. We aimed to determine if cancer aggressiveness correlates with androgen levels in patients undergoing radical prostatectomy for localized PCa. We performed a prospective, multicenter cohort study between June 2013 and June 2016, involving men with localized PCa scheduled to undergo radical prostatectomy. Clinical and hormonal patient data (testosterone deficiency, defined by total testosterone (TT) levels < 300 ng/dL and/or bioavailable testosterone (BT) levels < 80 ng/dL) were prospectively collected, along with pathological assessment of preoperative biopsy and subsequent radical prostatectomy specimens, using predominant Gleason pattern (prdGP) 3/4 grading. Of 1343 patients analyzed, 912 (68%) had prdGP3 PCa and 431 (32%) had high-grade (prdGP4, i.e., ISUP ≥ 3) disease on prostatectomy specimens. Only moderate concordance in prdGP scores between prostate biopsies and prostatectomy specimens was found. Compared with patients with prdGP3 tumors (i.e., ISUP ≤ 2), significantly more patients with prdGP4 cancers had demonstrable hypogonadism, characterized either by BT levels (17.4% vs. 10.7%, p < 0.001) or TT levels (14.2% vs. 9.7%, p = 0.020). BT levels were also lower in patients with prdGP4 tumors compared to those with prdGP3 disease. Testosterone deficiency (defined by TT and/or BT levels) was independently associated with higher PCa aggressiveness. BT is a predictive factor for prdGP4 disease, and evaluating both TT and BT to define hypogonadism is valuable in preoperative assessment of PCa (AndroCan Trial: NCT02235142).

Sex steroids in serum and prostatic tissue of human cancerous prostate (STERKPROSER trial).

BACKGROUND: Currently, there is no consensus regarding the expected concentration levels of intra-prostatic sex steroids in patients with Prostate Cancer (PCa). Our objective was to assess the concentration levels of sex steroids in prostatic tissue and serum, in two cohorts of patients with localized PCa or benign prostatic hyperplasia (BPH). METHODS: Between September 2014 and January 2017, men selected for radical cystectomy (for bladder cancer) or open prostatectomy (for BPH), and men selected for radical prostatectomy for localized PCa were included. Blood samples were collected at baseline before surgery, and steroid concentrations were assessed following the recommendations of the Endocrine Society. Intra-prostatic samples were collected from fresh surgical samples, and assessed by gas chromatography and mass spectrometry (GC/MS). Permanova analysis was performed. Analyses were adjusted for age, prostate weight, and prostate-specific antigen (PSA) level. RESULTS: A total of 73 patients (41 patients with PCa and 32 patients with BPH) were included in this study. Patients with PCa were younger, and had smaller prostate volumes with higher levels of PSA. The levels of Total Testosterone (TT), Di-Hydro-Testosterone (DHT), and Estradiol (E2) in the serum were not significantly different between PCa and BPH. In PCa tissue, TT concentrations were significantly lower (0.11 ng/g vs 0.47 ng/g, P = 0.0002), however its derivative E2 had significantly higher concentrations (31.0 ng/g vs 22.3 ng/g, P = 0.01). DHT tissue concentrations were not significantly different between the two groups (5.55 ng/g vs 5.42 ng/g, P = 0.70). Intra-prostatic TT concentrations were significantly lower in the peripheral zone than in the central zone for the CaP group (0.07 ng/g vs 0.15 ng/g, P = 0.004). CONCLUSIONS: Patients with PCa had lower intra-prostatic TT and higher E2 concentrations levels compared to the patients with BPH. PCa seem to consume more TT and produce more E2, especially in the peripheral zone.

Sexual steroids in serum and prostatic tissue of human non-cancerous prostate (STERPROSER trial).

BACKGROUND: The specific involvement of the sex steroids in the growth of the prostatic tissue remains unclear. Sex steroid concentrations in plasma and in fresh surgical samples of benign central prostate were correlated to prostate volume. METHODS: Monocentric prospective study performed between September 2014 and January 2017. Age, obesity parameters, and both serum and intraprostatic concentrations of sex steroids were collected complying with the latest Endocrine Society guidelines and the steroids assessed by GC/MS. Statistical calculations were adjusted for age and body mass index (BMI). RESULTS: Thirty-two patients, equally divided between normal- and high-volume prostate groups, were included in the analysis. High-volume prostate patients were older, heavier and had higher BMI. Comparison adjusted for age and BMI showed higher DHT concentrations in high-volume prostate. Both normal- and high-volume prostate tissues concentrate sex steroids in a similar way. Comparison of enzymatic activity surrogate marker ratios within tissue highlighted similar TT/E1 and TT/E2 ratios, and higher DHT/E1 ratio and lower DHT/PSA ratio in the high-volume prostates. CONCLUSIONS: STERPROSER trial provides evidence for higher DHT concentration in highvolume prostates, that could reflect either higher 5-alpha reductase expression or lower expression of downstream metabolizing enzymes such as 3a-hydoxysteroid dehydrogenase.

Obesity and hypogonadism are associated with an increased risk of predominant Gleason 4 pattern on radical prostatectomy specimen.

PURPOSE: To compare histological features of prostate cancer according to both obesity, defined by a body mass index (BMI) ≥30 kg/m2, and androgenic status in patients who underwent radical prostatectomy. MATERIALS AND METHODS: Between March 2007 and September 2013, clinical, pathological and biological data were prospectively collected for patients referred for radical prostatectomy in a single European center. Preoperative total testosterone (TT) and bioavailable testosterone (bioT) serum determinations were performed. The threshold for hypogonadism was set at TT <3 ng/mL. The preoperative PSA value was registered. Gleason score (GS) and predominant Gleason pattern (PrdGP) were determined in prostate tissue specimens, and crosschecked by two uro-pathologists. Statistical analyzes were done for PrdGP4 risk assessment. RESULTS: A total of 937 consecutive patients were included. One hundred and thirty-five filled the criterion for obesity (14.4%), out of which 42 had TT <3 ng/mL (31.1%), while in non-obese patients, only 97 had TT <3 ng/mL (12.0%). In prostate specimens, mean GS was 6.8±0.5: 291 patients (31.1%) had a PrdGP4. The incidence of PrdGP4 was higher (p<0.001) in the 135 obese patients [50% when hypogonadal (p<0.02) or 42% when eugonadal (p<0.005)] than in non-obese patients (28.9% and 27.1%, respectively). In multivariable analyzis for PrdGP4 risk, obesity, TT <3 ng/mL, PSA, and age were independent risk factors. CONCLUSIONS: Both obesity and hypogonadism are independent risk factors for PrdGP4 in patients who underwent radical prostatectomy and should be taken into account in localized prostate cancer management, to improve the therapeutic choice, especially when prostate sparing approach is considered.

Long-term follow-up of TaG1 non-muscle-invasive bladder cancer.

OBJECTIVES: To retrospectively assess the long-term outcome of patients initially diagnosed with TaG1 non-muscle-invasive bladder cancer (NMIBC) with no immediate postoperative instillation of intravesical chemotherapy and evaluate the reproducibility of the European Organization for Research and Treatment of Cancer (EORTC) scoring system for predicting bladder cancer outcome. METHODS AND MATERIALS: A retrospective analysis of 481 consecutive cases of initially diagnosed TaG1 NMIBC according to the 1973 World Health Organization classification between 1995 and 2008 in a single institution was performed. Time to first recurrence, time to progression to T1 or G3 bladder cancer, and time to progression to muscle-invasive bladder cancer were studied. Time to event distributions was estimated by means of cumulative incidence functions to accurately take into account the patients who died (competing risk) before recurrence or progression. The Harrell c statistic calculation was used for our study's data results as well the original data from EORTC to compare the predictive power of a survival model. RESULTS: The median follow-up was 88 months (interquartile range: 51-135 mo). The 10-year recurrence-free, T1 or G3 NMIBC progression-free, and muscle-invasive bladder cancer progression-free survival rates were 64.2%, 96.6%, and 97%, respectively. In multivariate analysis, tumor size and number of lesions were prognostic variables of the risk of recurrence. In our study and EORTC data sets, the Harrell c values obtained were c = 0.85 (95% CI: [0.75, 0.93]) and c = 0.85 (95% CI: [0.75, 0.93]), respectively. CONCLUSION: Our study reports a detailed and extensive outcome of TaG1 NMIBC treated by TURB with no immediate postoperative intravesical instillation of chemotherapy. Our results suggest that the EORTC is a useful external validation scoring system for predicting bladder cancer outcome.

Trends in renal function after radical cystectomy and ileal conduit diversion: new insights regarding estimated glomerular filtration rate variations.

INTRODUCTION: Our objectives were to evaluate the long-term renal function after radical cystectomy (RC) and ileal conduit diversion (ICD) and to analyze year-by-year the estimated glomerular filtration rate (eGFR) and morphologic upper urinary tract changes. PATIENTS AND METHODS: We retrospectively identified 226 patients who had undergone RC and ICD from 1980 to 2008, with regular postoperative follow-up visits. The eGFR was calculated using the Modification of Diet in Renal Disease equation at baseline and during follow-up. A decrease in renal function was defined as > 1 mL/min/1.73 m(2) annually. RESULTS: The median follow-up period after RC was 91 months (range, 61-235 months). The median eGFR decreased from 66 mL/min/1.73 m(2) (range, 17-139 mL/min/1.73 m(2)) to 59 mL/min/1.73 m(2) (range, 33-102 mL/min/1.73 m(2)). A rapid decline in renal function occurred during the first 2 postoperative years (-9 mL/min/1.73 m(2) and -4 mL/min/1.73 m(2) in the first and second year, respectively), with a moderate to slight decrease in the subsequent years. Urinary obstruction was diagnosed in 51 patients (23%). Among the patients who underwent prompt surgical treatment, we did not find any association with the eGFR decline (P = .8). CONCLUSION: Patients with urinary ICD have a lifelong risk of chronic kidney disease. Regular monitoring of renal function and the morphologic upper urinary tract will permit early diagnosis and treatment of modifiable factors, avoiding irreversible kidney damage.

Assessment of diagnostic gain with hexaminolevulinate (HAL) in the setting of newly diagnosed non-muscle-invasive bladder cancer with positive results on urine cytology.

OBJECTIVE: In accordance with the European Association of Urology guidelines, a second transurethral resection of the bladder (TURB) is recommended for high-grade or T1-category tumors. This practice brings into question the benefit of photodynamic diagnosis (PDD) in reducing the residual disease after TURB in patients with positive results on urine cytology showing high-grade cancer cells. METHODS AND MATERIALS: A prospective, bicentric, randomized study comparing white light cystoscopy (WLC)+PDD with hexaminolevulinate arm with WLC alone (control arm) during the first TURB in patients with primary non-muscle-invasive bladder cancer and with positive results on urine cytology showing high-grade cancer cells. Patients underwent a first TURB with WLC and PDD or WLC alone, and then a second TURB with WLC and PDD, after 4 to 6 weeks. The number of tumors visualized in WLC and PDD and histology of the TURB specimen was recorded to perform a statistical analysis comparing both the 2 arms. RESULTS: A total of 151 patients were enrolled (hexaminolevulinate, n = 72; control, n = 79). The number of visualized tumors did not increase with PDD in the first or second TURB. During the second TURB, the residual tumor rate was not reduced in patients who had PDD during the first TURB. No significant difference was observed regarding the pattern of category and grade, the size, and the recurrence and progression risks during either the first or the second TURB. CONCLUSIONS: In the setting of primary non-muscle-invasive bladder cancer with positive results on urine cytology, performing a second TURB allows to diagnose residual tumor in approximately half of the cases. This rate was not significantly reduced by the use of the PDD during the first TURB.

Modulation of nerve-evoked contractions by ß3-adrenoceptor agonism in human and rat isolated urinary bladder.

Activation of ß3-adrenoceptors has been shown to have a direct relaxant effect on urinary bladder smooth muscle from both rats and humans, however there are very few studies investigating the effects of ß3-adrenoceptor agonists on nerve-evoked bladder contractions. Therefore in the current study, the role of ß3-adrenoceptors in modulating efferent neurotransmission was evaluated. The effects of ß3-adrenoceptor agonism on neurogenic contractions induced by electrical field stimulation (EFS) were compared with effects on contractions induced by exogenous acetylcholine (Ach) and αß-methylene adenosine triphosphate (αß-meATP) in order to determine the site of action. Isoproterenol inhibited EFS-induced neurogenic contractions of human bladder (pD2=6.79; Emax=65%). The effect of isoproterenol was selectively inhibited by the ß3-adrenoceptor antagonist L-748,337 (pKB=7.34). Contractions induced by exogenous Ach (0.5-1µM) were inhibited 25% by isoproterenol (3µM) while contractions to 10Hz in the same strip were inhibited 67%. The selective ß3-adrenoceptor agonist CL-316,243 inhibited EFS-induced neurogenic contractions of rat bladder (pD2=7.83; Emax=65%). The effects of CL-316,243 were inhibited in a concentration dependent manner by L-748,337 (pA2=6.42). Contractions induced by exogenous Ach and αß-meATP were significantly inhibited by CL-316,243, 29% and 40%, respectively. These results demonstrate that the activation of ß3-adrenoceptors inhibits neurogenic contractions of both rat and human urinary bladder. Contractions induced by exogenously applied parasympathetic neurotransmitters are also inhibited by ß3-agonism however the effect is clearly less than on neurogenic contractions (particularly in human), suggesting that in addition to a direct effect on smooth muscle, activation of prejunctional ß3-adrenoceptors may inhibit neurotransmitter release.

Long-term women-reported quality of life after radical cystectomy and orthotopic ileal neobladder reconstruction.

BACKGROUND: The purpose of this study was to determine health-related quality of life (HRQoL) among long-term disease-free survivors in women who underwent radical cystectomy (RC) for urothelial carcinoma and orthotopic ileal neobladder (ONB) reconstruction, using validated patient-reported outcome instruments. METHODS: From 2000 to 2011, a total of 46 women with urothelial bladder carcinoma had RC and ONB at our institution; 31 (67 %) eligible women completed 3 validated questionnaires: the medical outcome study short form 12 (SF-12), the urinary symptom profile, and the Contilife, respectively evaluating general HRQoL, voiding function, and urinary incontinence specific HRQoL. Unadjusted analyses were performed to analyze standardized measures of HRQoL and voiding symptoms; p < 0.05 was considered significant. RESULTS: The mean follow-up was 5.7 years; 24 women (77 %) considered their health as good, very good, or excellent. The SF-12 physical and mental scores were not significantly different between the population study and the general population (p > 0.05). A total of 20 women (65 %) declared to be fully continent. Daytime incontinence, nighttime incontinence, and hypercontinence were reported by 26, 29, and 31 % of women, respectively. On unadjusted analysis, incontinence was associated with age > 65 years at the time of surgery (p < 0.001). Hypercontinence was not associated with any variable. CONCLUSIONS: This study suggests that in the setting of radical cystectomy in women, ileal neobladder reconstruction provides long-term satisfaction with maintained HRQoL. For properly selected women, orthotopic neobladder can be considered an appropriate diversion choice.

Patterns of local recurrence after radical cystectomy in a contemporary series of patients with muscle-invasive bladder cancer.

PURPOSE: To describe the epidemiology, clinical features, and prognostic factors of local recurrence (LR) in a large case series of patients treated by radical cystectomy (RC) for bladder cancer. METHODS: A retrospective study was conducted on 903 patients treated in a single tertiary reference center. All cases of LR were identified. Descriptive analysis was performed on the clinical features, evolution, and overall mortality of these patients. Prognostic factors of LR were assessed using the Mann-Whitney test for continuous variables and the χ(2) test for categorical variables. RESULTS: Fifty-three patients were diagnosed with LR during follow-up (5.9 %). One patient had concomitant distant metastasis. Pain was the most frequent symptom leading to diagnosis. Mean time interval from RC to LR was 14.4 ± 13 months (1-64) with 50 % of cases diagnosed in the first postoperative year. Overall median survival of patients diagnosed with LR was 9 months [95 % confidence interval (6-11)]. Advanced pathological stage (T3 or T4) and lymph-node invasion were associated with increased LR rate in univariate and multivariate analysis. Presence of squamous cell carcinoma (SCC) was associated with a poorer prognosis after LR compared to pure urothelial carcinoma (p = 0.04). None of the parameters tested was associated with time interval between RC and LR diagnosis. CONCLUSIONS: LR is not uncommon, favored by high pathological stage (T3/T4), and has a very bad prognosis, particularly when SCC is present. LR must be carefully tracked during follow-up after RC, and optimal management of these cases remains to be determined.

Perivesical fat invasion in bladder cancer: implications for prognosis comparing pT2b, pT3a and pT3b stages and consequences for adjuvant chemotherapy indications.

UNLABELLED: Study Type--Therapy (retrospective cohort) Level of Evidence 2b. What's known on the subject? and What does the study add? The more that bladder cancer progresses from the urothelium to the outside of the bladder the worse the prognosis. To date, the use of adjuvant chemotherapy has not been completely defined. The present study clarifies the prognosis and benefits of adjuvant chemotherapy for different stages of bladder cancer that invade perivesical fat. OBJECTIVE: • To assess the prognosis of pT2b, pT3a and pT3b bladder cancers after radical cystectomy (RC) in order to define potential situations where chemotherapy may be of benefit. PATIENTS AND METHODS: • Between 1985 and 2009, 903 patients underwent a RC and pelvic bilateral lymphadenectomy in an Institutional Referral Centre. • In all, 87 patients (9.6%) had a pT2b tumour, 111 patients (12.3%) a pT3a tumour, and 129 patients (14.3%) a pT3b tumour. • The median (range) overall follow-up was 23 (1-350) months. • Overall (OS), disease-specific (DSS), metastases-free (MFS) and local recurrence-free survival (LRFS) was estimated and compared using Kaplan-Meier plots and log-rank test. RESULTS: • The 5-year survivals pT2b and pT3a were similar for LRFS (86% vs 84%), MFS (69% vs 63%), DSS (72% vs 70%) and OS (66% vs 61%), and the prognosis was better than for pT3b stage tumours (69%, 44%, 40%, and 31% respectively). • In pN0 disease, MFS differences between pT2b-pT3a and pT3b tumours were not significant in patients who had received adjuvant chemotherapy (MSF of 87%, 69% and 56%, respectively) while they were significant in patients without adjuvant chemotherapy (MFS of 70%, 68% and 42%, respectively). CONCLUSIONS: • Bladder cancers invading perivesical tissue macroscopically have a greater propensity to produce lymph node metastases, local recurrence, and have lower MFS, DSS, and OS. In pN0 disease, pT3b tumours may receive more benefit from adjuvant chemotherapy. • Our results could be a useful for selecting patients for adjuvant chemotherapy.