Surgical metastasectomy for metastatic renal cell carcinoma in the era of targeted and immune therapy: a narrative review.

PURPOSE: Metastatic renal cell carcinoma (mRCC) still harbours a big propensity for future metastasis. Combinations of immune and targeted therapies are currently the cornerstone of management with a less clear role for surgical metastasectomy (SM). METHODS: We performed a narrative review of literature searching for the available evidence on the yield of surgical metastasectomy in the era of targeted and immune therapies. The review consisted of a PubMed search of relevant articles using the Mesh terms:" renal cell carcinoma", "surgery¼, «resection", "metastasectomy", "molecular targeted therapies", "immune checkpoint inhibitors" alone or in combination. RESULTS: In this review, we exposed the place of surgical metastasectomy within a multimodal treatment algorithm for mRCC Also, we detailed the patient selection criteria that yielded the best results when SM was performed. Finally, we discussed the feasibility and advantages of SM per organ site. CONCLUSION: Our work was able to show that SM could be proposed as a consolidation treatment to excise residual lesions that were deemed unresectable prior to a combination of systemic therapies. Contrastingly, it can be proposed as an upfront treatment, leaving systemic therapies as an alternative in case of future relapse. However, patient selection regarding their performance status, metastatic sites, number of lesions and tumorous characteristics is of paramount importance.

Proteogenomic Characterization of Bladder Cancer Reveals Sensitivity to Apoptosis Induced by Tumor Necrosis Factor-related Apoptosis-inducing Ligand in FGFR3-mutated Tumors.

BACKGROUND: Molecular understanding of muscle-invasive (MIBC) and non-muscle-invasive (NMIBC) bladder cancer is currently based primarily on transcriptomic and genomic analyses. OBJECTIVE: To conduct proteogenomic analyses to gain insights into bladder cancer (BC) heterogeneity and identify underlying processes specific to tumor subgroups and therapeutic outcomes. DESIGN, SETTING, AND PARTICIPANTS: Proteomic data were obtained for 40 MIBC and 23 NMIBC cases for which transcriptomic and genomic data were already available. Four BC-derived cell lines harboring FGFR3 alterations were tested with interventions. INTERVENTION: Recombinant tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), second mitochondrial-derived activator of caspases mimetic (birinapant), pan-FGFR inhibitor (erdafitinib), and FGFR3 knockdown. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Proteomic groups from unsupervised analyses (uPGs) were characterized using clinicopathological, proteomic, genomic, transcriptomic, and pathway enrichment analyses. Additional enrichment analyses were performed for FGFR3-mutated tumors. Treatment effects on cell viability for FGFR3-altered cell lines were evaluated. Synergistic treatment effects were evaluated using the zero interaction potency model. RESULTS AND LIMITATIONS: Five uPGs, covering both NMIBC and MIBC, were identified and bore coarse-grained similarity to transcriptomic subtypes underlying common features of these different entities; uPG-E was associated with the Ta pathway and enriched in FGFR3 mutations. Our analyses also highlighted enrichment of proteins involved in apoptosis in FGFR3-mutated tumors, not captured through transcriptomics. Genetic and pharmacological inhibition demonstrated that FGFR3 activation regulates TRAIL receptor expression and sensitizes cells to TRAIL-mediated apoptosis, further increased by combination with birinapant. CONCLUSIONS: This proteogenomic study provides a comprehensive resource for investigating NMIBC and MIBC heterogeneity and highlights the potential of TRAIL-induced apoptosis as a treatment option for FGFR3-mutated bladder tumors, warranting a clinical investigation. PATIENT SUMMARY: We integrated proteomics, genomics, and transcriptomics to refine molecular classification of bladder cancer, which, combined with clinical and pathological classification, should lead to more appropriate management of patients. Moreover, we identified new biological processes altered in FGFR3-mutated tumors and showed that inducing apoptosis represents a new potential therapeutic option.

Cohort profile: COBLAnCE: a French prospective cohort to study prognostic and predictive factors in bladder cancer and to generate real-world data on treatment patterns, resource use and quality of life.

PURPOSE: Bladder cancer is a complex disease with a wide range of outcomes. Clinicopathological factors only partially explain the variability between patients in prognosis and treatment response. There is a need for large cohorts collecting extensive data and biological samples to: (1) investigate gene-environment interactions, pathological/molecular classification and biomarker discovery; and (2) describe treatment patterns, outcomes, resource use and quality of life in a real-world setting. PARTICIPANTS: COBLAnCE (COhort to study BLAdder CancEr) is a French national prospective cohort of patients with bladder cancer recruited between 2012 and 2018 and followed for 6 years. Data on patient and tumour characteristics, treatments, outcomes and biological samples are collected at enrolment and during the follow-up. FINDINGS TO DATE: We describe the cohort at enrolment according to baseline surgery and tumour type. In total, 1800 patients were included: 1114 patients with non-muscle-invasive bladder cancer (NMIBC) and 76 patients with muscle-invasive bladder cancer (MIBC) had transurethral resection of a bladder tumour without cystectomy, and 610 patients with NMIBC or MIBC underwent cystectomy. Most patients had a solitary lesion (56.3%) without basement membrane invasion (71.7% of Ta and/or Tis). Half of the patients with cystectomy were stage ≤T2 and 60% had non-continent diversion. Surgery included local (n=298) or super-extended lymph node dissections (n=11) and prostate removal (n=492). Among women, 16.5% underwent cystectomy and 81.4% anterior pelvectomy. FUTURE PLANS: COBLAnCE will be used for long-term studies of bladder cancer with focus on clinicopathological factors and molecular markers. It will lead to a much-needed improvement in the understanding of the disease. The cohort provides valuable real-world data, enabling researchers to study various research questions, assess routine medical practices and guide medical decision-making.

Correction: Diamant et al. Effectiveness of Early Radical Cystectomy for High-Risk Non-Muscle Invasive Bladder Cancer. Cancers 2022, 14, 3797.

In the original article [...].

Effectiveness of Early Radical Cystectomy for High-Risk Non-Muscle Invasive Bladder Cancer.

Purpose: The purpose of this study is to compare perioperative and oncological outcomes of upfront vs. delayed early radical cystectomy (eRC) for high-risk non-muscle-invasive bladder cancer (HR-NMIBC). Methods: All consecutive HR-NMIBC patients who underwent eRC between 2001 and 2020 were retrospectively included and divided into upfront and delayed groups, according to the receipt or not of BCG. Perioperative outcomes were evaluated and the impact of upfront vs. delayed eRC on pathological upstaging, defined as ≥pT2N0 disease at final pathology, was assessed using multivariable logistic regression. Recurrence-free (RFS), cancer-specific (CSS) and overall survival (OS) were compared between upfront and delayed eRC groups using inverse probability of treatment weighting (IPTW)-adjusted Cox model. Results: Overall, 184 patients received either upfront (n = 87; 47%) or delayed (n = 97; 53%) eRC. No difference was observed in perioperative outcomes between the two treatment groups (all p > 0.05). Pathological upstaging occurred in 55 (30%) patients and upfront eRC was an independent predictor (HR = 2.65; 95% CI = (1.23−5.67); p = 0.012). In the IPTW-adjusted Cox analysis, there was no significant difference between upfront and delayed eRC in terms of RFS (HR = 1.31; 95% CI = (0.72−2.39); p = 0.38), CSS (HR = 1.09; 95% CI = (0.51−2.34); p = 0.82) and OS (HR = 1.19; 95% CI = (0.62−2.78); p = 0.60). Conclusion: our results suggest similar perioperative outcomes between upfront and delayed eRC, with an increased risk of upstaging after upfront eRC that did impact survival, as compared to delayed eRC.

Multilayer spectrum of intratumoral heterogeneity in basal bladder cancer.

Basal/squamous (Ba/Sq) subtype represents an intrinsic and robust group in the consensus molecular classification of muscle-invasive bladder cancer (MIBC), with poor outcome and controversial chemosensitivity. We aimed to investigate the spectrum of intratumor heterogeneity (ITH) in the Ba/Sq subtype. First, we validated a 29-gene NanoString CodeSet to predict the Ba/Sq subtype for FFPE samples. We identified heterogeneous Ba/Sq tumors in a series of 331 MIBC FFPE samples using dual GATA3/KRT5/6 immunohistochemistry (IHC). Heterogeneous regions with distinct immunostaining patterns were studied separately for gene expression using the 29-gene CodeSet, for mutations by targeted next-generation sequencing, and for copy number alteration (CNA) by microarray hybridization. Among 83 Ba/Sq tumors identified by GATA3/KRT5/6 dual staining, 19 tumors showed heterogeneity at the IHC level. In one third of the 19 cases, regions from the same tumor were classified in different distinct molecular subtypes. The mutational and CNA profiles confirmed the same clonal origin for IHC heterogeneous regions with possible subclonal evolution. Overall, two patterns of intratumoral heterogeneity (ITH) were observed in Ba/Sq tumors: low ITH (regions with distinct immunostaining, but common molecular subtype and shared CNA) or high ITH (regions with distinct immunostaining, molecular subtype, and CNA). These results showed multilayer heterogeneity in Ba/Sq MIBC. In view of personalized medicine, this heterogeneity adds complexity and should be taken into account for sampling procedures used for diagnosis and treatment choice. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Complications and Discharge after Radical Cystectomy for Older Patients with Muscle-Invasive Bladder Cancer: The ELCAPA-27 Cohort Study.

Radical cystectomy is the standard of care for localized bladder cancer but is associated with high morbidity and mortality rates-especially among older patients with comorbidities. The association between geriatric assessment parameters on post-operative complications and discharge has not previously been investigated. The present analysis of the Elderly Cancer Patient (ELCAPA) prospective cohort included all patients aged ≥70 having undergone a geriatric assessment and then radical cystectomy for localized muscle-invasive bladder cancer between 2007 and 2018. The primary endpoint was the proportion of patients with one or more complications in the first 30 days after cystectomy. The secondary endpoints were the length of hospital stay (LOS), the 30-day mortality, and discharge rates. Sixty-two patients (median age: 81; range: 79-83.8) were included. The 30-day complication rate was 73%, and 49% of the patients had experienced a major complication, according to the Clavien-Dindo classification. The 30-day mortality rate was 4%. None of the geriatric, oncological, or laboratory parameters were significantly associated with the occurrence or severity of complications. The median (interquartile range) LOS was 18 days (15-23) overall and was longer in patients with complications (19 days vs. 15 days in those without complications; p = 0.013). Thirty days after cystectomy, 25 patients (53%) had been discharged to home and 22 (47%) were still in a rehabilitation unit. In a univariate analysis, a Geriatric-8 score ≤ 14, a loss of one point on the Activities of Daily Living Scale, anemia, at least one grade ≥ 3 comorbidity on the Cumulative Illness Rating Scale-Geriatric, and an inpatient geriatric assessment were associated with a risk of not being discharged to home. In older patients having undergone a geriatric assessment, radical cystectomy is associated with a high complication rate, a longer LOS, and functional decline at 30 days.

Comparison of the iliac, vaginal and umbilical graft extraction in robot-assisted laparoscopic living donor nephrectomy.

PURPOSE: To compare different extractions routes for robot-assisted living donor nephrectomy in terms of post-operative pain and renal function recovery. METHODS: Live donor kidney transplantation data from our institution were reviewed from November 2011 to March 2017. Postoperative pain was estimated using cumulative painkillers consumption. Variables were compared between the 3 groups with ANOVA for continuous data, χ2 test for categorial data. A survival analysis with Kaplan-Meier curve assessing time to transplant recipient nadir was performed to compare the renal function recovery. RESULTS: Sixty-three RLDN were performed (23 iliac, 23 vaginal and 17 umbilical extractions). There was no significant difference between the three groups in terms of operative time, blood lost, warm ischemia time, cumulative painkiller consumption and renal function recovery time. Postoperative complications for Umbilical, Vaginal and Iliac were, respectively, of 0, 3 and 1. No major difference was found between the 3 groups beside a slightly longer hospital stay in the iliac group. CONCLUSION: Iliac incision might impact post-operative pain with a moderate but significant longer hospital stay. Vaginal extraction is an option when cosmetic outcomes present a real demand. The three options appeared to be safe and should be discussed with the patient in regard of the surgeon experience.

Hemostatic radiotherapy for bladder cancer-related hematuria in patients unfit for surgery: is there any impact of fractionation schedule?

PURPOSE: The optimal schedule for palliative external beam radiotherapy (EBRT) in patients with bladder tumors with hematuria unfit for surgery remains undefined. This study aimed to assess the clinical hemostatic efficacy and safety of two EBRT hypofractionated schedules. METHODS: From February 2008 to October 2017, 31 patients were referred to our department for palliative hemostatic bladder irradiation. EBRT consisted of two schedules: "continuous" treatment (CRT) was delivered following consecutive 3-10 weekdays (3-6Gy/fraction (fr), to a total dose of 18-30Gy) (n=14); the "discontinuous" schedule (DRT) consisted of 23Gy in 4fr (6.5Gy/fr on days 1 and 3, followed by 5Gy/fr on days 15 and 17; n=12). The primary endpoint was the rate of hemostatic control (HC) at the end of the radiation course. Other endpoints included mid-term HC, toxicities and overall survival. Comparative analyses were performed by exact Fisher test with a cut-off of 0.05 for statistical significance. RESULTS: The rate of HC at the end of EBRT was 92% (n=24) with no differences between CRT and DRT (100% vs 86%; p=0.48). The median follow-up was 6 months, HC was achieved in 15/26 (58%) patients at the last follow-up, without meaningful differences between CRT and DRT (50% vs 67%; p=0.45). Three and two patients developed acute grade ≤2 diarrhea in CRT and DRT groups, respectively. CONCLUSION: Our study suggests that both hypofractionated "continuous" and "discontinuous" EBRT are well tolerated and represent acceptable schedules for patients with limited life expectancy. DRT schedule could be preferred for departments' organization to increase the slots for the treatment of other referred patients for radiotherapy.

Robotic versus open radical cystectomy throughout the learning phase: insights from a real-life multicenter study.

BACKGROUND AND OBJECTIVES: Robot-assisted radical cystectomy (RARC) has been shown to be non-inferior to open radical cystectomy (ORC) for the treatment of bladder cancer (BC). However, most data on RARC come from high-volume surgeons at high-volume centers. The objective of the study was to compare perioperative and mid-term oncologic outcomes of RARC versus ORC in a real-life cohort of patients treated by surgeons starting their experience with RARC. MATERIALS AND METHODS: Data were prospectively collected from consecutive patients undergoing RARC and ORC at five referral Centers between 2010 and 2016 by five surgeons (one per center) with no prior experience in RARC. Patients with high-risk non-muscle-invasive or organ-confined muscle-invasive (T2N0M0) bladder cancer were considered for RARC. The main study endpoints were perioperative outcomes, postoperative surgical complications, and mid-term oncologic outcomes. RESULTS: Overall, 124 and 118 patients underwent RARC and ORC, respectively. Baseline patients' and tumors' characteristics were comparable between the two groups. Yet, the proportion of patients receiving neoadjuvant chemotherapy was significantly higher in the RARC cohort. Median operative time was significantly higher, while median EBL, LOH, and transfusion rates were significantly lower after RARC. Median number of lymph nodes removed was significantly higher after RARC. All other histopathological outcomes, as well as the rate of early (< 30 days) and late postoperative complications, were comparable to ORC. At a median follow-up of 2 years, 29 (23%) and 41 (35%) patients developed disease recurrence (p = 0.05), while 20 (16%) and 37 (31%) died of bladder cancer (p = 0.005) after RARC and ORC, respectively. CONCLUSIONS: With proper patient selection, RARC was non-inferior to ORC throughout the surgeons' learning phase. Yet, the observed differences in oncologic outcomes suggest selection bias toward adoption of RARC for patients with more favorable disease characteristics.

Extraperitoneal Robot-Assisted Vesicourethral Reconstruction to Manage Anastomotic Stricture Following Radical Prostatectomy.

OBJECTIVE: To demonstrate the feasibility of robot-assisted vesicourethral reconstruction. Vesicourethral anastomotic stricture following radical prostatectomy is a real challenge for reconstructive surgery when facing several endoscopic management failures. MATERIAL AND METHODS: This is a case series of robot-assisted vesicourethral reconstruction for anastomotic stricture failing endoscopic management. The procedure was performed with an extraperitoneal approach. The fibrotic anastomotic region was resected and a new vesicourethral running suture was performed with well-vascularized tissue. Bladder catheter was removed after 7 days. RESULTS: Six procedures were performed from April 2013 to May 2018 at our department. One patient had a robot-assisted radical prostatectomy at our department; the 5 others were referred from other institutions after receiving open prostatectomies. Three patients had salvage radiation therapy before reconstruction. Mean age was of 73.8 years (68-82). There was no peroperative complication. Mean operative time was of 108 minutes (60-180)], with a mean estimated blood loss of 130 mL (50-300). After surgery, 3 patients presented recurrences managed endoscopically without recurrence after 3, 5, and 11 months. Three patients presented incontinence treated with artificial sphincter implantation. One patient had no residual symptom after 5 years of follow-up. CONCLUSIONS: Robot-assisted vesicourethral reconstruction is a safe procedure. It is an option to consider when facing recurring anastomotic stricture following radical prostatectomy. It is an alternative to the perineal approach and an option before urinary diversion. Patients should be informed of the risks of incontinence and recurrence before surgery especially if they had radiation therapy.

Perioperative outcomes and complications of intracorporeal vs extracorporeal urinary diversion after robot-assisted radical cystectomy for bladder cancer: a real-life, multi-institutional french study.

PURPOSE: To compare perioperative outcomes and complications of extracorporeal (ECUD) vs intracorporeal urinary diversion (ICUD) in patients after undergoing robot-assisted radical cystectomy (RARC) at five referral centers in France. METHODS: We retrospectively reviewed our multi-institutional, prospectively-collected database to select patients undergoing RARC between 2010 and 2016 with at least 3 months of follow-up. At each center, the surgery was performed by one surgeon with extensive experience in robotic surgery and radical cystectomy but no prior experience in RARC. RESULTS: Overall, 108 patients were included. ECUD and ICUD were performed in 34 (31.5%) and 74 (68.5%) patients, respectively. Patient characteristics were comparable among the two groups, except for a higher proportion of patients with high surgical risk (ASA score ≥ 3) in the ECUD group. Ileal conduit and ileal neobladder were performed in 63/108 (58%) and 45/108 (42%) cases, respectively. Ileal conduit was performed more often with an extracorporeal approach while ileal neobladder with an intracorporeal approach. Overall, operative time, length of hospital stay, positive margin rate, and number of lymph nodes removed did not significantly differ among the two cohorts. Estimated blood loss and transfusion rates were significantly higher in the ECUD group. Rate of early (38.2 vs 47.3%, p = 0.4) and late (29.4 vs 18.9%, p = 0.2) surgical complications did not significantly differ between the ECUD and ICUD groups. Results were comparable in the subgroup analysis in the ileal conduit subpopulation. CONCLUSION: In our real-life, multi-institutional study, RARC with ICUD achieved perioperative outcomes and complication rates comparable to those of RARC with ECUD.

Reappraisal of HER2 status in the spectrum of advanced urothelial carcinoma: a need of guidelines for treatment eligibility.

Although human epidermal growth factor receptor 2 (HER2) may represent a therapeutic target, its evaluation in urothelial carcinoma of the bladder does not rely on a standardized scoring system by immunohistochemistry or fluorescent in situ hybridization (FISH), as reflected by various methodology in the literature and clinical trials. Our aim was to improve and standardize HER2 amplification detection in bladder cancer. We assessed immunohistochemical criteria derived from 2013 American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAPs) guidelines for breast cancer and investigated intratumoral heterogeneity in a retrospective multicentric cohort of 188 patients with locally advanced urothelial carcinoma of the bladder. Immunohistochemistry was performed on 178 primary tumors and 126 lymph node metastases, eligible cases (moderate/strong, complete/incomplete membrane staining) were assessed by FISH. HER2 overexpression was more frequent with 2013 ASCO/CAP than 2007 ASCO/CAP guidelines (p < 0.0001). The rate of positive HER2 FISH was similar between primary tumor and lymph node metastases (8%). Among positive FISH cases, 48% were associated with moderate/strong incomplete membrane staining that were not scored eligible for FISH by 2007 ASCO/CAP criteria. Among 3+ immunohistochemistry score cases, 67% were associated with HER2-positive FISH. Concordance between primary tumors and matched lymph node metastases was moderate for immunohistochemistry (κ = 0.54 (CI 95%, 0.41-0.67)) and FISH (κ = 0.50 (CI 95%, 0.20-0.79)). HER2-positive FISH was more frequent in micropapillary carcinomas (12%) and carcinoma with squamous differentiation (11%) than in pure conventional carcinoma (6%). Intratumoral heterogeneity for HER2 immunohistochemistry was observed in 7% primary tumor and 6% lymph node metastases; 24% positive HER2 FISH presented intratumoral heterogeneity. Our study suggests that HER2 evaluation should include an immunohistochemistry screening step with eligibility for FISH including incomplete/complete and moderate/strong membrane staining. Spatial or temporal intratumoral heterogeneity prompts to perform evaluation on both tumor and lymph node, and for each histological variant observed.

Frequency and prognostic significance of incidental prostate cancer at radical cystectomy: Results from an international retrospective study.

OBJECTIVES: To analyze the frequency of incidental prostate cancer (PC) at radical cystoprostatectomy (RC) for urothelial carcinoma of the bladder (UCB) and its association with survival outcomes in an international cohort. PATIENTS AND METHODS: In this retrospective study, we included 2114 who underwent RC and lymphadenectomy for UCB between 1976 and 2012 male patients from seven institutions. Univariable and multivariable Cox regression models addressed the association of incidental PC with cancer-specific mortality and overall mortality after RC. RESULTS: Overall, incidental PC was found in 513 (24.3%) patients with the lowest frequency in a Japanese center (23/164, 11.2%) and the highest frequency in a North American center (122/325, 37.5%), respectively (p < 0.001). Within a median follow up of 27 months (IQR: 50 months), 20 patients (3.9%) were diagnosed with biochemical recurrence (BCR) and none of the patients died of PC. PC pathological tumor stage was more advanced in patients experiencing BCR (p < 0.001). In multivariable Cox regression analyses adjusted for standard clinicopathologic features, incidental PC was not associated with cancer-specific (HR: 1.11, 95% CI: 0.91-1.35, p = 0.30) or overall mortality (HR: 1.06, 95% CI: 0.83-1.35, p = 0.65). CONCLUSIONS: Incidental PC at RC for UCB is a frequent event. However, the majority of PC cases are well-differentiated and organ-confined. Presence of incidental PC shows significant geographic differences. The risk of BCR after incidental PC is low and incidental PC is not associated with survival in UCB patients treated with RC.

Predictive factors for final pathologic ureteral sections on 700 radical cystectomy specimens: Implications for intraoperative frozen section decision-making.

PURPOSE: To identify preoperative predictive factors for final ureteral section invasion after radical cystectomy (RC) and to validate significant factors on an external independent cohort. MATERIAL AND METHODS: We retrospectively reviewed data of all consecutive RC performed for bladder cancer in 2 high-volume institutions. Clinical, pathological, and follow-up data were collected prospectively and reviewed retrospectively. Pathological evaluation was performed by 2 well-trained uropathologists in each center. Logistic regression analyses were performed to identify predictive factors for final ureteral sections involvement. Significant factors in cohort A were validated in cohort B. Receiver operating curve and area under curve were modeled to evaluate predictive accuracy of the markers. RESULTS: A total of 441 RC were performed in center A and 307 RC were performed in center B. Mean follow-ups were 36.2 and 38.1 months, respectively. Invasion of the final ureteral section was observed on 5.5% of patients in cohort A and 4.8% of patients in cohort B. In cohort A, multivariable logistic regression identified preoperative hydronephrosis on computed tomography scan (odds ratio [OR] = 4.9, P = 0.004) and presence of Carcinoma in situ (CIS, OR = 3.9, P = 0.01) as the only factors associated with ureteral sections positivity. In cohort B, hydronephrosis and CIS were both associated with ureteral sections positivity in univariable analysis. In multivariable analysis, only hydronephrosis remained significant (OR = 5.9, P = 0.01). Predictive accuracy of hydronephrosis and CIS combined in 1 variable was 0.72. CONCLUSION: Hydronephrosis and bladder CIS have good accuracy in predicting ureteral sections positivity after RC. In the presence of those factors, ureteral frozen sections should be performed.

Adjuvant Chemotherapy After Radical Cystectomy for Urothelial Bladder Cancer: Outcome and Prognostic Factors for Survival in a French Multicenter, Contemporary Cohort.

BACKGROUND: In the past decade, adjuvant chemotherapy (AC) after radical cystectomy (RC) was preferred worldwide for patients with muscle-invasive urothelial bladder cancer. In this study we aimed to determine the outcome of patients who received AC and evaluated prognostic factors associated with survival. PATIENTS AND METHODS: We retrospectively analyzed 226 consecutive patients treated in 6 academic hospitals between 2000 and 2009. Multivariate Cox proportional hazards regression adjusted for center to estimate adjusted hazard ratios (HRs) with 95% confidence intervals were used. RESULTS: The median age was 62.4 (range, 35-82) years. Patients had pT3/pT4 and/or pN+ in 180 (79.6%) and 168 patients (74.3%), respectively. Median lymph node (LN) density was 25% (range, 3.1-100). Median time between RC and AC was 61.5 (range, 18-162) days. Gemcitabine with cisplatin, gemcitabine with carboplatin, and MVAC (methotrexate, vinblastine, doxorubicin, and cisplatin) regimens were delivered in 161 (71.2%), 49 (21.7%), and 12 patients (5.3%) of patients, respectively. The median number of cycles was 4 (range, 1-6). Thirteen patients (5.7%) with LN metastases also received adjuvant pelvic radiotherapy (ART). After a median follow-up of 4.2 years, 5-year overall survival (OS) was 40.7%. In multivariate analysis, pT ≥3 stage (HR, 1.73; P = .05), LN density >50% (HR, 1.94; P = .03), and number of AC cycles <4 (HR, 4.26; P = .001) were adverse prognostic factors for OS. ART (HR, 0.30; P = .05) tended to provide survival benefit. CONCLUSION: Classical prognostic features associated with survival are not modified by the use of AC. Patients who derived benefit from AC had a low LN density and received at least 4 cycles of treatment.

Clinicopathological characteristics of urothelial bladder cancer in patients less than 40 years old.

Urothelial bladder cancer (UBC) is rare in young patients and as a result little information as to tumor type and clinical course are available. We present clinicopathological data of a large series of patients less than 40 years with bladder carcinoma. We included in this retrospective study covering the period from 1992 to 2013 patients less than 40 years with a first diagnosis of bladder cancer. Lesions were classified according to the WHO 2004 classification by uropathologists of ten centers. Stage, grade, multifocality, smoking habits, recurrence, and survival were studied. The cohort comprised of 152 patients, 113 males and 39 females with a mean age of 33.2 years. The large majority of the patients (142) was diagnosed with an urothelial carcinoma, the ten others with various histopathological diagnoses. In the age group less than 30 years old, 40.3 % of the cases concerned a papillary urothelial neoplasia of low malignant potential (PUNLMP). In the age group over 30 years, the proportion of PUNLMP decreased to 27.2 %. Only 5.6 % of the UBC was associated with carcinoma in situ. In 14.1 %, a high grade muscle invasive UC was found; 7.0 % had lymph node and 4.9 % distant metastasis at time of presentation. Four patients presented with a history of schistosomiasis; all had an infiltrating carcinoma. After initial resection, 36 patients relapsed, 17 % as PUNLMP, 53 % as pTa low grade, and 30 % as pTa-pT2 high grade UC. During follow-up, 6 % of the patients died. PUNLMP is the most frequent entity in this patient group. It is important that the PUNLMP entity is maintained in future classification systems.

International Prostate Symptom Score is a predictive factor of lower urinary tract symptoms after radical prostatectomy.

OBJECTIVE: To evaluate the impact of radical prostatectomy on lower urinary tract symptoms by using the International Prostate Symptom Score and International Prostate Symptom Score quality of life. METHODS: The present prospective study comprised 804 patients having localized prostate cancer who underwent radical prostatectomy. International Prostate Symptom Score and International Prostate Symptom Score quality of life were recorded preoperatively, and at 1, 3, 6, 12 and 24 months. Two study groups were considered: group 1 included patients with International Prostate Symptom Score ≤7 (mild) and group 2 included patients with International Prostate Symptom Score ≥8 (moderate to severe). Student's t-test and logistic regression were carried out to detect a predictive factor of International Prostate Symptom Score ≤7 at 24 months. RESULTS: The mean International Prostate Symptom Score was 5.58 ± 6.6, 11.12 ± 7.1 and 7.62 ± 6 at baseline, 1 month and 3 months, respectively (P <0.0001). The mean quality of life score showed the same evolution with a significant difference at 1 and 3 months. The mean International Prostate Symptom Score was initially 1.57 ± 1.9 in group 1 and 13.51 ± 5.5 in group 2 (P <0.0001), evolving to 3.41 ± 3.1 and 7.69 ± 5.8 at 24 months (P <0.0001), respectively. The mean quality of life score was significantly different between the groups initially, and at 6 and 12 months with P <0.0001, P = 0.005 and P = 0.02, respectively. The multivariate logistic regression showed that age, prostate volume and preoperative International Prostate Symptom Score were independent predictive factors of International Prostate Symptom Score ≤7 at 24 months (P <0.0001). In group 2, 47 patients (17%) had an International Prostate Symptom Score ≥8 at 24 months, 15 of them (32%) having a QoL score ≥3. CONCLUSIONS: The present study shows the beneficial impact of radical prostatectomy on lower urinary tract symptoms. However, a proportion of patients with a baseline International Prostate Symptom Score ≥8 maintain the same score at 24 months, with worsening in quality of life score in one-third of them.

Prognostic Model for Predicting Survival in Patients with Disease Recurrence Following Radical Cystectomy.

BACKGROUND: Although the natural history of urothelial carcinoma of the bladder (UCB) from radical cystectomy (RC) to disease recurrence (DR) has been investigated intensively, the course of patients who have experienced DR after RC for UCB remains poorly understood. OBJECTIVE: To evaluate the prognostic value of the Bajorin criteria that consists of two risk factors: Karnofsky performance status (KPS) and the presence of visceral metastases (VMs) in patients with DR after RC for UCB. Furthermore, to identify additional factors associated with cancer-specific mortality (CSM) and thus build a multivariable model to predict survival after DR. DESIGN, SETTING, AND PARTICIPANTS: We identified 967 patients with UCB who underwent RC at 17 centers between 1979 and 2012 and experienced DR. Of these, 372 patients had complete data we used for analysis. OUTCOMES MEASUREMENTS AND STATISTICAL ANALYSIS: Univariable Cox regressions analysis was performed. We used a forward stepwise selection process for our final multivariable model. RESULTS AND LIMITATIONS: Within a median follow-up of 18 mo, 266 patients died of disease. Cancer-specific survival at 1 yr was 79%, 76%, and 47% for patients with no (n=105), one (n=180), and two (n=87) risk factors (p<0.001; c-index: 0.604). On multivariable analyses, we found that KPS <80%, higher American Society of Anesthesiologists score, anemia, leukocytosis, and shorter time to DR (all p values <0.034) were independently associated with increased CSM. The combination of time to DR and KPS resulted in improved discrimination (c-index: 0.694). CONCLUSIONS: We confirmed the prognostic value of KPS and VMs in patients with DR following RC for UCB. We also found several other clinical variables to be associated with worse CSM. We developed a model for predicting survival after DR inclusive of time to DR and KPS assessed at DR. If validated, this model could help clinical trial design. PATIENT SUMMARY: We developed a model to predict survival following disease recurrence after radical cystectomy for urothelial carcinoma of the bladder, based on time to disease recurrence and Karnofsky performance status.