Perioperative dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin in muscle-invasive bladder cancer (VESPER): survival endpoints at 5 years in an open-label, randomised, phase 3 study.

BACKGROUND: The optimal perioperative chemotherapy for patients with muscle-invasive bladder cancer is not defined. The VESPER (French Genito-Urinary Tumor Group and French Association of Urology V05) trial reported improved 3-year progression-free survival with dose-dense methotrexate, vinblastine, doxorubicin and cisplatin (dd-MVAC) versus gemcitabine and cisplatin (GC) in patients who received neoadjuvant therapy, but not in the overall perioperative setting. In this Article, we report on the secondary endpoints of overall survival and time to death due to bladder cancer at 5-year follow-up. METHODS: VESPER was an open-label, randomised, phase 3 trial done at 28 university hospitals or comprehensive cancer centres in France, in which adults (age ≤18 years and ≤80 years) with primary bladder cancer and histologically confirmed muscle-invasive urothelial carcinoma were randomly allocated (1:1; block size four) to treatment with dd-MVAC (every 2 weeks for a total of six cycles) or GC (every 3 weeks for a total of four cycles). Overall survival and time to death due to bladder cancer (presented as 5-year cumulative incidence of death due to bladder cancer) was analysed by intention to treat (ITT) in all randomly assigned patients. Overall survival was assessed by the Kaplan-Meier method with the treatment groups compared with log-rank test stratified for mode of administration of chemotherapy (neoadjuvant or adjuvant) and lymph node involvement. Time to death due to bladder cancer was analysed with an Aalen model for competing risks and a Fine and Gray regression model stratified for the same two covariates. Results were presented for the total perioperative population and for the neoadjuvant and adjuvant subgroups. The trial is registered with ClinicalTrials.gov, NCT01812369, and is complete. FINDINGS: From Feb 25, 2013, to March 1, 2018, 500 patients were randomly assigned, of whom 493 were included in the final ITT population (245 [50%] in the GC group and 248 [50%] in the dd-MVAC group; 408 [83%] male and 85 [17%] female). 437 (89%) patients received neoadjuvant chemotherapy. Median follow-up was 5·3 years (IQR 5·1-5·4); 190 deaths at the 5-year cutoff were reported. In the perioperative setting (total ITT population), we found no evidence of association of overall survival at 5 years with dd-MVAC treatment versus GC treatment (64% [95% CI 58-70] vs 56% [50-63], stratified hazard ratio [HRstrat] 0·79 [95% CI 0·59-1·05]). Time to death due to bladder cancer was increased in the dd-MVAC group compared with in the GC group (5-year cumulative incidence of death: 27% [95% CI 21-32] vs 40% [34-46], HRstrat 0·61 [95% CI 0·45-0·84]). In the neoadjuvant subgroup, overall survival at 5 years was improved in the dd-MVAC group versus the GC group (66% [95% CI 60-73] vs 57% [50-64], HR 0·71 [95% CI 0·52-0·97]), as was time to death due to bladder cancer (5-year cumulative incidence: 24% [18-30] vs 38% [32-45], HR 0·55 [0·39-0·78]). In the adjuvant subgroup, the results were not conclusive due to the small sample size. Bladder cancer progression was the cause of death for 157 (83%) of the 190 deaths; other causes of death included cardiovascular events (eight [4%] deaths), deaths related to chemotherapy toxicity (four [2%]), and secondary cancers (four [2%]). INTERPRETATION: Our results on overall survival at 5 years were in accordance with the primary endpoint analysis (3-year progression-free survival). We found no evidence of improved overall survival with dd-MVAC over GC in the perioperative setting, but the data support the use of six cycles of dd-MVAC over four cycles of GC in the neoadjuvant setting. These results should impact practice and future trials of immunotherapy in bladder cancer. FUNDING: French National Cancer Institute.

Benign Prostatic Hyperplasia Endoscopic Surgical Procedures in Kidney Transplant Recipients: A Comparison Between Holmium Laser Enucleation of the Prostate, GreenLight Photoselective Vaporization of the Prostate, and Transurethral Resection of the Prostate.

Purpose: The main objective of this multicentric retrospective pilot study was to evaluate the 1-year follow-up safety (i.e., minor [Clavien-Dindo I-II] and major [Clavien-Dindo ≥III] complications) of holmium laser enucleation of the prostate (HoLEP), GreenLight photoselective vaporization of the prostate (GL PVP), and transurethral resection of the prostate (TURP) performed after kidney transplantation (KT). The secondary objectives were to evaluate the efficacy and to assess the impact of these procedures on graft function. Materials and Methods: We retrospectively included all KT recipients who underwent a HoLEP or GL PVP or TURP for benign prostatic hyperplasia (BPH) in three French university centers. Results: From January 2013 to April 2018, 60 BPH endoscopic surgical procedures in KT recipients were performed: 17 HoLEP (HoLEP group), 9 GL PVP (GL PVP group), and 34 TURP (TURP group). Age, body mass index, preoperative serum creatinine, preoperative International Prostatic Symptom Score, preoperative Qmax, preoperative prostate-specific antigen, medical history of acute urinary retention (AUR), urinary tract infection (UTI), and indwelling urethral catheter were similar in all study groups. Mean preoperative prostate volume was higher in HoLEP group. The rate of overall postoperative complications was statistically higher in the HoLEP group (11/17 [64.7%] vs 1/9 [11.1%] vs 12/34 [35.3%] in HoLEP group, GL PVP group, and TURP group, respectively, p = 0.02), with higher rate of long-term UTI and AUR. Qmax improved in all groups after operation. Delta postoperative month 12-preoperative serum creatinine was similar in the all groups. Conclusions: Although our study is underpowered, the rate of postoperative complications is higher with HoLEP procedure, in comparison with GL PVP, for the treatment of BPH after KT. One-year efficacy is similar in HoLEP, GL PVP, and TURP groups. Further prospective randomized controlled trials are needed to confirm our results.

Evaluation of the impact of a clinical pathway on the progression of acute urinary retention.

AIMS: The management of acute urinary retention (AUR) revolves around trial without catheter (TWOC) after prescription of an alpha-blocker. This study evaluates the implementation of a clinical pathway for AUR. METHODS: Specific clinical pathways for AUR was established between the Emergency Department and the Department of Urology in order to reduce the duration of bladder drainage that included standard prescriptions, an information sheet, and a note to be faxed to scheduling nurses to organize the trial without catheter (TWOC). The main endpoint was the reduction in the time between the AUR episode and TWOC, without decreasing urination. RESULTS: Between April 2015 and December 2016, 248 patients were treated in the Emergency Department, and externally, for AUR. One hundred and seventy patients were enrolled in the pathway group and 78 in the control group. The mean duration of urinary catheterization decreased by 5.5 days as did the number of patients lost to follow-up (32% vs 76%), without decreasing the successful voiding (46% vs 36%). The duration of the urinary catheterization was not related to the chance of successful voiding regardless of the urine volume and a drainage time of over 10 days significantly reduced the chance of success (68%, n = 26 versus 42%, n = 76; P = 0.0038). CONCLUSION: The implementation of a clinical pathway for AUR reduced the number of patients lost to follow-up and the catheterization duration, thus optimizing the management of these patients.

Management of Node Only Recurrence after Primary Local Treatment for Prostate Cancer: A Systematic Review of the Literature.

PURPOSE: We analyzed all available studies assessing the management of node only recurrence after primary local treatment of prostate cancer. MATERIALS AND METHODS: We systematically reviewed the literature in January 2015 using the PubMed, Web of Sciences and Embase databases according to PRISMA guidelines. Studies exclusively reporting visceral or bone metastatic disease were excluded from analysis. Eight radiotherapy and 12 salvage lymph node dissection series were included in our qualitative study. RESULTS: All 248 radiotherapy and 480 salvage lymph node dissection studies were single arm case series including a total of 728 patients. Choline positron emission tomography/computerized tomography was the reference imaging technique for nodal recurrence detection. Globally 50% of patients remained disease-free after short-term followup. Nevertheless, approximately two-thirds of patients received adjuvant hormone therapy, leading an overestimation of prostate specific antigen-free survival rates obtained after salvage treatment. Combining radiotherapy with salvage lymph node dissection may improve oncologic control in the treated region without improving the outfield relapse risk or the prostate specific antigen response. Great heterogeneity among series in adjuvant treatments, endpoints, progression definitions and study populations made it difficult to assess the precise impact of salvage treatment on the prostate specific antigen response and compare outcomes between radiotherapy and salvage lymph node dissection series. Toxicity after radiotherapy or salvage lymph node dissection was acceptable without frequent high grade complications. The benefit of early hormone therapy as the only salvage treatment remains unknown. CONCLUSIONS: Although a high level of evidence is currently missing to draw any strong conclusion, published clinical series show that in select patients salvage treatment directed to nodal recurrence could lead to good oncologic outcomes. Although the optimal timing of androgen deprivation therapy in this setting is still unknown, such an approach could delay time to systemic treatment with an acceptable safety profile. Future prospective trials are awaited to better clarify this potential impact on well-defined endpoints.

Neoadjuvant targeted molecular therapies in patients undergoing nephrectomy and inferior vena cava thrombectomy: is it useful?

OBJECTIVE: To assess the effect of neoadjuvant targeted molecular therapies (TMTs) on size and level of inferior vena cava tumor thrombi and to evaluate their impact on surgical management. METHODS: We retrospectively analyzed the data of 14 patients treated for a clear cell renal cell carcinoma with inferior vena cava thrombi by neoadjuvant TMT before nephrectomy. Clinical, pathological and perioperative data were gathered retrospectively at each institution. The primitive tumor size and the thrombus size were defined by computed tomography before TMT. The tumor thrombus level was defined according to the Novick's classification. RESULTS: Before TMT, thrombus level was staged I for 1 (7%), II for 10 (72%) and III (21%) for 3 patients. First-line therapy was sunitinib in 11 cases and sorafenib in 3 cases. Median therapy duration was two cycles (1-5). Three patients experienced major adverse effects (grade III) during TMT. Following TMT, 6 (43%) patients had a measurable decrease, 6 (43%) had no change, and 2 (14%) had an increase in the thrombus. One patient (7%) had a downstage of thrombus level, 12 (85%) had stable thrombi, and 1 (7%) had an upstage. Regarding primary tumor, 7 (50%), 5 (36%) and 2 (14%) patients had a decrease, stabilization and an increase in tumor size, respectively. CONCLUSION: Neoadjuvant TMT appears to have limited effects on renal tumor thrombi. This retrospective study failed to demonstrate a significant impact of neoadjuvant TMT on surgical management of clear cell renal cell carcinoma with inferior vena cava tumor thrombi.