Alexandra Masson-Lecomte

Conditional Survival After Radical Cystectomy for Bladder Cancer: Evidence for a Patient Changing Risk Profile over Time

BACKGROUND Standard survival statistics do not take into consideration the changes in the weight of individual variables at subsequent times after the diagnosis and initial treatment of bladder cancer. OBJECTIVE To assess the changes in 5-yr conditional survival (CS) rates after radical cystectomy for bladder cancer and to determine how well-established prognostic factors evolve over time. DESIGN, SETTING, AND PARTICIPANTS We analyzed data from 8141 patients treated with radical cystectomy at 15 international academic centers between 1979 and 2012. INTERVENTIONS Radical cystectomy and pelvic lymph node dissection. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Conditional cancer-specific survival (CSS) and overall survival (OS) estimates were calculated using the Kaplan-Meier method. The multivariable Cox regression model was used to calculate proportional hazard ratios for the prediction of mortality after stratification by clinical characteristics (age, perioperative chemotherapy status) and pathologic characteristics (pT stage, grade, lymphovascular invasion, pN stage, number of nodes removed, margin status). The median follow-up was 32 mo. RESULTS AND LIMITATIONS The 5-yr CSS and OS rates were 67.7% and 57.5%, respectively. Given a 1-, 2-, 3-, 5- and 10-yr survivorship, the 5-yr conditional OS rates improved by +5.6 (60.7%), +8.4 (65.8%), +7.6 (70.8%), +3.0 (72.9%), and +1.9% (74.3%), respectively. The 5-yr conditional CSS rates improved by +5.6 (71.5%), +9.8 (78.5%), +7.9 (84.7%), +7.2 (90.8%), and 5.6% (95.9%), respectively. The 5- and 10-yr CS improvement was primarily noted among surviving patients with advanced stage disease. The impact of pathologic parameters on CS estimates decreased over time for both CSS and OS. Findings were confirmed on multivariable analyses. The main limitation was the retrospective design. CONCLUSIONS CS analysis demonstrates that the patient risk profile changes over time. The risk of mortality decreases with increasing survivorship. The CS rates improve mainly in the case of advanced stage disease. The impact of prognostic pathologic features decreases over time and can disappear for long-term CS.

A prospective comparison of surgical and pathological outcomes obtained after robot‐assisted or pure laparoscopic partial nephrectomy in moderate to complex renal tumours: results from a French multicentre collaborative study

Nephron‐sparing surgery has become the standard of care for small renal masses because it allows for the same oncological control as radical nephrectomy and achieves better overall survival, while lowering the risk of subsequent chronic renal failure. Mini‐invasive surgical approaches have also been developed, e.g. laparoscopic partial nephrectomy (LPN) and robot‐assisted laparoscopic PN (RAPN), which result in less bleeding, reduced postoperative pain, shorter length of stay (LOS) and shorter recovery time. LPN requires advanced surgical skill, has a longer learning curve and requires perseverance, which limits its large diffusion. From this prospective comparative study, we can now claim that RAPN is not inferior to pure LPN in terms of perioperative outcomes (i.e. blood loss, operative duration, warm ischaemia time, LOS).

Gender-specific differences in clinicopathologic outcomes following radical cystectomy: An international multi-institutional study of more than 8000 patients

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.

Early unclamping technique during robot-assisted laparoscopic partial nephrectomy can minimise warm ischaemia without increasing morbidity.

To compare perioperative outcomes of early unclamping (EUC) vs standard unclamping (SUC) during robot‐assisted partial nephrectomy (RAPN), as early unclamping of the renal pedicle has been reported to decrease warm ischaemia time (WIT) during laparoscopic PN.

Radical Prostatectomy for High-risk Prostate Cancer Defined by Preoperative Criteria: Oncologic Follow-up in National Multicenter Study in 813 Patients and Assessment of Easy-to-use Prognostic Substratification

OBJECTIVE To estimate the effect of predictive factors for oncologic outcomes after radical prostatectomy (RP) for high-risk prostate cancer (PCa). METHODS A total of 813 patients underwent RP for high-risk PCa in a national retrospective multi-institutional study. High-risk PCa was defined as follows: prostate-specific antigen (PSA) level>20 ng/mL, Gleason score 8-10, and/or clinical Stage T2c-T4 disease. The preoperative criteria of high-risk PCa were studied in a logistic regression model to assess the correlations with the pathologic findings in the RP specimens. The predictive factors isolated or combined in scores were assessed by Cox multivariate and Kaplan-Meier analyses in predicting PSA failure (recurrence-free survival [RFS]) and overall survival (OS). RESULTS The median follow-up was 64 months. Organ-confined disease was reported in 36.5%. The 5-year RFS, metastasis-free survival, and OS rate was 74.1%, 96.1%, and 98.6%, respectively. Each preoperative criteria of high-risk PCa was an independent predictor of PSA failure. The PSA failure risk was increased by 1.5- and 2.8-fold in men with 2 and 3 criteria, respectively. The RFS, but not the OS, was significantly different according to the preoperative score (P<.001). The postoperative score was significantly predictive for RFS and OS (P<.001 and P<.035, respectively). The risk of PSA failure was significantly increased with an increasing postoperative score (2-4.6-fold). CONCLUSION National data support evidence that RP can result in encouraging midterm oncologic outcomes for the management of high-risk PCa. At 5 years after surgery, 75% of patients remain disease free. Our easy-to-use risk stratification might help clinicians to better predict the clinical and PSA outcomes of high-risk patients after surgery.

Recommandations en onco-urologie 2016-2018 du CCAFU : Tumeurs de la vessie

OBJECTIVE The purpose of the guidelines national committee CCAFU on bladder cancer was to propose updated french guidelines for non-muscle invasive (NMIBC) and invasive (MIBC) bladder cancers. METHODS A Medline search was achieved between 2013 and 2016, as regards diagnosis, options of treatment and follow-up of bladder cancer, to evaluate different references with levels of evidence. RESULTS Diagnosis of NMIBC (Ta, T1, CIS) is based on a complete deep resection of the tumour. The use of fluorescence and a second-look indication are essential to improve initial diagnosis. Risks of both recurrence and progression can be estimated using the EORTC score. A stratification of patients into low, intermediate and high risk groups is pivotal for recommending adjuvant treatment : instillation of chemotherapy (immediate post-operative, standard schedule) or intravesical BCG (standard schedule and maintenance). Cystectomy is recommended in BCG-refractory patients. Extension evaluation of MIBC is based on pelvic-abdominal and thoracic CT-scan; MRI and FDG-PET remain optional. Cystectomy associated with extensive pelvic lymph nodes resection is considered the gold standard for non metastatic MIBC. An orthotopic bladder substitution should be proposed to both male and female patients lacking any contraindications and in cases of negative frozen urethral samples. The interest of neoadjuvant chemotherapy is well known for all MIBC, wathever the stage. Thus, neoadjuvant chemotherapy is recommended for all eligible patients according PS (PS <2) and renal function (clearance > 60ml/mn). As regards metastatic MIBC, first-line chemotherapy using platin is recommended (GC or MVAC). In second line treatment, only chemotherapy using vinflunine has been validated to date, even if results of immunotherapy clinical trials are encouraging. CONCLUSION These updated french guidelines will contribute to increase the level of urological care for the diagnosis and treatment for NMIBC and MIBC.

High-flow Priapism Due to a Malignant Glomus Tumor (Glomangiosarcoma) of the Corpus Cavernosum

INTRODUCTION The major cause of non-ischemic high-flow priapism is post-traumatic vascular injury leading to an arterio-lacunar fistula. However, rare causes such as tumors may induce priapism. This is the first report of a malignant glomus tumor localized in the corpora cavernosa. AIM The aim of this case is to emphasize the importance of the initial management of priapism and to suggest new tracks on the tests to be performed when the usual exams are not sufficient. METHOD We report the case of a hypervascular penile tumor responsible for high-flow priapism as the first clinical symptom of a metastatic glomus tumor. The persistent penile tumescence was initially considered to be a stuttering priapism and treated using an oral α-adrenergic as no provoking event nor fistula was found. After a 2-week reluctance, a penile magnetic resonance imaging (MRI) was performed. RESULTS The MRI showed a hypervascular lesion at the proximal part of the right corpora. The lesion was considered as a fistula, and a selective embolization was performed. Two weeks after embolization, the patient came back to the emergency room because of syncopes and dyspnea. Examination by cardiac ultrasound and chest computed tomography revealed the presence of cardiac, pulmonary, and subcutaneous malignant glomus tumors (glomangiosarcoma). Patient received three lines of chemotherapy, and the penile tumor was surgically removed because of persistent erectile dysfunction and perineal pain. CONCLUSION This case supports the use of corporal body blood gas analysis in difficult cases to discriminate high- and low-flow priapism and penile MRI when clinical history, physical examination, and aspiration are not contributory.

Off-Clamp versus On-Clamp Robotic Partial Nephrectomy: A Multicenter Match-Paired Case-Control Study

Introduction: The aim of this study was to compare the outcomes of on-clamp and off-clamp robotic partial nephrectomy (RPN). Materials and Methods: The charts of all patients who underwent an RPN at 8 institutions between 2010 and 2014 were retrospectively reviewed. The patients who underwent an off-clamp RPN were matched to on-clamp RPN in a 1-4 fashion according to the following variables: RENAL score, tumor size and surgeons experience. Pre-, intra-, and postoperative data were compared between both groups. Results: Among 525 RPN, 26 were performed off-clamp (5%). They were matched to 104 on-clamp RPN. The complications rate (15.5 vs. 7.7%, p = 0.53), major complications rate (4.9 vs. 3.9%; p = 0.82), and transfusions rate (0 vs. 4.9%; p = 0.58) did not differ significantly between the clamped and unclamped groups. Conversely, estimated blood loss was higher in the off-clamp group (266.4 vs. 284.6 mL, p = 0.048) and so was the rate of conversion to radical nephrectomy (0 vs. 7.7%, p = 0.04). Postoperative preservation of renal function was comparable in both groups. Conclusion: Off-clamp RPN is feasible for a small subgroup of renal tumors without increased risk of postoperative complications but at the cost of higher estimated blood loss and increased risk of conversion to radical nephrectomy.

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.

Prediction of non-muscle-invasive bladder cancer recurrence by measurement of checkpoint HLAG’s receptor ILT2 on peripheral CD8 + T cells

Background and Objective Recurrence of non-muscle invasive bladder cancer (NMIBC) after initial management occurs in 60–70% of patients. Predictive criteria for recurrence remain only clinical and pathological. The aim of this study was to investigate the prognostic significance of the proportion of checkpoint HLA-G’s receptor ILT2-expressing peripheral CD8+ T cells. Results The proportion of CD4+ILT2+and CD8+ILT2+ T cells was not increased in NMIBC compared to controls. However, a strong association was found between recurrence and CD8+ILT2+ T cell population levels (p = 0.0006). Two-year recurrence-free survival was 83% in patients with less than 18% CD8+ILT2+ T cells, 39% in the intermediary group, and 12% in patients with more than 46% CD8+ILT2+ T cells. Multivariate analyses demonstrated that the proportion of CD8+ILT2+ T cells was an independent predictive factor for recurrence. Adding CD8+ILT2+ T cells population level to clinical variables increased the predictive accuracy of the model by 4.5%. Materials and Methods All patients treated for NMIBC between 2012 and 2014 were included prospectively. Blood samples, tumor and clinico-pathological characteristics were collected. HLA-G expression was measured using IHC, and CD8+ILT2+ T cell levels using flow cytometry. Association between HLA-G and CD8+ILT2+ T cell population levels with NMIBC risk of recurrence was investigated using Cox regression analyses. Prediction was measured using the concordance index statistic. Conclusions We demonstrated a strong association between the proportion of circulating CD8+ILT2+ T cells and NMIBC risk of recurrence. Gain in prediction was substantial. If externally validated, such immunological marker could be integrated to predict NMIBC recurrence.