Muscle-invasive bladder carcinoma (MIBC) constitutes a heterogeneous group of tumors with a poor outcome. Molecular stratification of MIBC may identify clinically relevant tumor subgroups and help to ...provide effective targeted therapies. From seven series of large-scale transcriptomic data (383 tumors), we identified an MIBC subgroup accounting for 23.5% of MIBC, associated with shorter survival and displaying a basal-like phenotype, as shown by the expression of epithelial basal cell markers. Basal-like tumors presented an activation of the epidermal growth factor receptor (EGFR) pathway linked to frequent EGFR gains and activation of an EGFR autocrine loop. We used a 40-gene expression classifier derived from human tumors to identify human bladder cancer cell lines and a chemically induced mouse model of bladder cancer corresponding to human basal-like bladder cancer. We showed, in both models, that tumor cells were sensitive to anti-EGFR therapy. Our findings provide preclinical proof of concept that anti-EGFR therapy can be used to target a subset of particularly aggressive MIBC tumors expressing basal cell markers and provide diagnostic tools for identifying these tumors.
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.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract Background In spite of the increasing use of robot-assisted radical prostatectomy (RALP) worldwide, no level 1 evidence-based benefit favouring RALP versus pure laparoscopic approaches has ...been demonstrated in extraperitoneal laparoscopic procedures. Objective To compare the operative, functional, and oncologic outcomes between pure laparoscopic radical prostatectomy (LRP) and RALP. Design, setting, and participants From 2001 to 2011, 2386 extraperitoneal LRPs were performed consecutively in cases of localised prostate cancers. Intervention A total of 1377 LRPs and 1009 RALPs were performed using an extraperitoneal approach. Outcome measurements and statistical analysis Patient demographics, surgical parameters, pathologic features, and functional outcomes were collected into a prospective database and compared between LRP and RALP. Biochemical recurrence–free survival was tested using the Kaplan-Meier method. Mean follow-up was 39 and 15.4 mo in the LRP and RALP groups, respectively. Results and limitations Shorter durations of operative time and of hospital stay were reported in the RALP group compared with the LRP group ( p < 0.001) even beyond the 100 first cases. Mean blood loss was significantly lower in the RALP group ( p < 0.001). The overall rate and the severity of the complications did not differ between the two groups. In pT2 disease, lower rates of positive margins were reported in the RALP group ( p = 0.030; odds ratio OR: 0.396) in multivariable analyses. The surgical approach did not affect the continence recovery. Robot assistance was independently predictive for potency recovery ( p = 0.045; OR: 5.9). Survival analyses showed an equal oncologic control between the two groups. Limitations were the lack of randomisation and the short-term follow-up. Conclusions Robotic assistance using an extraperitoneal approach offers better results than pure laparoscopy in terms of operative time, blood loss, and hospital stay. The robotic approach independently improves the potency recovery but not the continence recovery. When strict indications of nerve-sparing techniques are respected, RALP gives better results than LRP in terms of surgical margins in pathologically organ-confined disease. Longer follow-up is justified to reach conclusions on oncologic outcomes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The PI3K/AKT pathway is considered to play a major role in bladder carcinogenesis, but its relationships with other molecular alterations observed in bladder cancer remain unknown. We investigated ...PI3K/AKT pathway activation in a series of human bladder urothelial carcinomas (UC) according to PTEN expression, PTEN deletions and FGFR3, PIK3CA, KRAS, HRAS, NRAS and TP53 gene mutations. The series included 6 normal bladder urothelial samples and 129 UC (Ta n = 25, T1 n = 34, T2–T3–T4 n = 70). Expression of phospho‐AKT (pAKT), phospho‐S6‐Ribosomal Protein (pS6) (one downstream effector of PI3K/AKT pathway) and PTEN was evaluated by reverse phase protein Array. Expression of miR‐21, miR‐19a and miR‐222, known to regulate PTEN expression, was also evaluated. pAKT expression levels were higher in tumors than in normal urothelium (p < 0.01), regardless of stage and showed a weak and positive correlation with pS6 (Spearman coefficient RS = 0.26; p = 0.002). No association was observed between pAKT or pS6 expression and the gene mutations studied. PTEN expression was decreased in PTEN‐deleted tumors, and in T1 (p = 0.0089) and T2–T3–T4 (p < 0.001) tumors compared to Ta tumors; it was also negatively correlated with miR‐19a (RS = −0.50; p = 0.0088) and miR‐222 (RS = −0.48; p = 0.0132), but not miR‐21 (RS = −0.27; p = 0.18) expression. pAKT and PTEN expressions were not negatively correlated, and, on the opposite, a positive and moderate correlation was observed in Ta (RS = 0.54; p = 0.0056) and T1 (RS = 0.56; p = 0.0006) tumors. Our study suggests that PI3K/AKT pathway activation occurs in the entire spectrum of bladder UC regardless of stage or known most frequent molecular alterations, and independently of low PTEN expression.
What's new?
Although a suspected player in bladder carcinogenesis, involvement of the PI3K/AKT pathway in human bladder urothelial carcinoma (UC) has been little explored. Here, reverse phase protein array was used to investigate PI3K/AKT pathway activation and expression of PTEN, a PI3K/AKT pathway downregulator, in a series of human UCs characterized by genetic alterations frequently observed in UC. Analysis revealed elevated pAKT expression and PI3K/AKT pathway activation across UCs, despite the different molecular alterations and independent of the loss of PTEN. The findings support the idea that the PI3K/AKT pathway is of therapeutic significance in UC.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Abstract Background The impact of gender on the staging and prognosis of urothelial carcinoma of the bladder (UCB) is insufficiently understood. Objective To assess gender-specific differences in ...pathologic factors and survival of UCB patients treated with radical cystectomy (RC). Design, setting, and participants Data from 8102 patients treated with RC (6497 men 80% and 1605 women 20%) for UCB between 1971 and 2012 were analyzed. Outcome measurements and statistical analysis Multivariable competing-risk regression analyses were performed to evaluate the relationship of gender on disease recurrence (DR) and cancer-specific mortality (CSM). We also tested the interaction of gender and tumor stage, nodal status, and lymphovascular invasion (LVI). Results and limitations Female patients were older at the time of RC ( p = 0.033) and had higher rates of pathologic stage T3/T4 disease ( p < 0.001). In univariable, but not in multivariable analysis, female gender was associated with a higher risk of DR ( p = 0.022 and p = 0.11, respectively). Female gender was an independent predictor for CSM ( p = 0.004). We did not find a significant interaction between gender and stage, nodal metastasis, or LVI (all p values >0.05). Conclusions We found female gender to be associated with a higher risk of CSM following RC. However, these findings do not appear to be explained by gender differences in pathologic stage, nodal status, or LVI. This gender disparity may be due to differences in care and/or the biology of UCB.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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,
χ
2
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.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Purpose: Clinically useful molecular markers predicting the clinical course of patients diagnosed with non–muscle-invasive bladder
cancer are needed to improve treatment outcome. Here, we validated ...four previously reported gene expression signatures for
molecular diagnosis of disease stage and carcinoma in situ (CIS) and for predicting disease recurrence and progression.
Experimental Design: We analyzed tumors from 404 patients diagnosed with bladder cancer in hospitals in Denmark, Sweden, England, Spain, and France
using custom microarrays. Molecular classifications were compared with pathologic diagnosis and clinical outcome.
Results: Classification of disease stage using a 52-gene classifier was found to be highly significantly correlated with pathologic
stage ( P < 0.001). Furthermore, the classifier added information regarding disease progression of T a or T 1 tumors ( P < 0.001). The molecular 88-gene progression classifier was highly significantly correlated with progression-free survival
( P < 0.001) and cancer-specific survival ( P = 0.001). Multivariate Cox regression analysis showed the progression classifier to be an independently significant variable
associated with disease progression after adjustment for age, sex, stage, grade, and treatment (hazard ratio, 2.3; P = 0.007). The diagnosis of CIS using a 68-gene classifier showed a highly significant correlation with histopathologic CIS
diagnosis (odds ratio, 5.8; P < 0.001) in multivariate logistic regression analysis.
Conclusion: This multicenter validation study confirms in an independent series the clinical utility of molecular classifiers to predict
the outcome of patients initially diagnosed with non–muscle-invasive bladder cancer. This information may be useful to better
guide patient treatment.
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.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
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