Bladder mapping of tumour recurrence after radical nephroureterectomy for upper tract urothelial carcinoma and its influence on oncological outcomes.

OBJECTIVES: To assess the location of intravesical recurrence (IVR) after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC), to determine the main predictive factors for IVR in the bladder-cuff area (BCA), and to assess the effect of BCA recurrence (BCAR) on prognosis. PATIENTS AND METHODS: This was a multicentre, retrospective study using the French collaborative database on UTUC, which includes data for all patients treated in 24 referral uro-oncology centres across the country. All patients who underwent RNU with bladder-cuff excision and who developed IVR between 1995 and 2010 were selected. Patients were divided into two groups: Group A: BCAR; and Group B: recurrence elsewhere in the bladder. The Kaplan-Meier method was used to estimate the probability of BCAR-free survival. Groups were compared using the log-rank test. Independent risk factors for BCAR were identified using a Cox proportional hazard regression model, with univariate and multivariate analyses. RESULTS: Overall, 163 patients were included in the final analysis: Group A, 87 patients (53.4%) and Group B, 76 (46.6%). The clinicopathological characteristics were similar in the groups. The median (interquartile range [IQR]) follow-up was 36 (31.7-40.39) months. The median (IQR) time to IVR was 10.0 (8.6-13.39) months [Group A: 11.0 (8.8-13.2)  months vs Group B: 10.0 (8.5-11.5) months; P = 0.35]. The probability of BCAR at 1, 2, and 3 years was 45.5% (95% confidence interval [CI] 40.1-50.9), 17.9% (95% CI 13.7-22.1), and 10.8% (95% CI 7.4-14.2) respectively, whereas the probability of recurrence elsewhere in the bladder was 42.1% (95% CI 36.4-47.8), 14.7% (95% CI 10.6-18.8), and 4.4% (95% CI 1.9-6.9), respectively (P = 0.35). Pathological tumour stage (≥pT3) was significantly related to the risk of BCAR (P = 0.03). CONCLUSION: There were more BCARs after RNU in advanced UTUC. However, no preferred site for recurrence was detected.

Robotic radical nephroureterectomy and segmental ureterectomy for upper tract urothelial carcinoma: a multi-institutional experience.

PURPOSE: To report a multi-institutional experience on robotic radical nephroureterectomy (RNU) and segmental ureterectomy (SU) for upper tract urothelial carcinoma (UTUC). METHODS: Data were prospectively collected from patients with non-metastatic UTUC undergoing robotic SU or RNU at three referral centers between 2015 and 2018. Transperitoneal, single-docking robotic RNU followed established principles. Bladder cuff excision (BCE) was performed with robotic or open approach. Techniques for SU included: ureteral resection and primary uretero-ureterostomy; partial pyelectomy and modified pyeloplasty; ureteral resection with BCE and direct- or psoas hitch-ureteroneocystostomy. We retrospectively evaluated the technical feasibility, and peri-operative and oncologic outcomes after robotic RNU/SU. RESULTS: 81 patients were included. No case required conversion to open surgery. Early major (Clavien-Dindo grade > 2) complications were reported in six (7.4%) patients (two after SU, four after RNU). Three patients experienced late major complications (one after SU, two after RNU). Median ΔeGFR at 3 months was - 1 ml/min/1.73 m2 after SU and - 15 ml/min/1.73 m2 after RNU. Positive surgical margins were recorded in five patients (one after SU, four after RNU). Median follow-up was 21 months and 22 months in the SU and RNU groups, respectively. Three (20%) patients had ipsilateral upper tract recurrence after SU, while five (7.5%) developed metastases after RNU. No case of port-site metastases or peritoneal carcinomatosis was reported. At last follow-up, 67 (82.7%) patients were alive without evidence of disease. CONCLUSION: Robotic SU and RNU are technically feasible and achieved promising peri-operative and oncologic outcomes in selected patients with non-metastatic UTUC.

Outcomes after salvage radical prostatectomy and first-line radiation therapy or HIFU for recurrent localized prostate cancer: results from a multicenter study.

INTRODUCTION: Despite no consensus on the optimal management of recurrent prostate cancer after primary radiation or HIFU therapy, salvage prostatectomy (sRP) is reserved for only 3% of patients because of technical challenges and frequent post-operative complications. We assessed outcomes after sRP in a series of patients with localized PCa and that had received radiation therapy or HIFU as a first-line treatment. MATERIALS AND METHODS: Data from nine French referral centers on patients treated with sRP between 2005 and 2017 were collected. Pre- and post-operative data, including oncological and functional outcomes after first treatment and sRP, were analyzed to determine the predictors for biochemical recurrence (BCR) and cancer-specific survival (CSS) after sRP. RESULTS: First-line treatments were external beam-radiation therapy (EBRT) for 30 (55%), brachytherapy (BT) for 10 (18%), and high-intensity focused ultrasound (HIFU) for 15 (27%). Median (IQR) PSA at diagnosis was 6.4 (4.9-9.5) ng/mL, median PSA at nadir was 1.9 (0.7-3.0) ng/mL, and median (IQR) to first BCR was 13 (6-20) months. Of the 55 patients, 44 (80%) received robot-assisted salvage radical prostatectomy and 11 (20%) received salvage retropubic radical prostatectomy. Restoration of continence was achieved in 90% of preoperatively continent patients; 24% that had received nerve-sparing (NS) procedures were potent after surgery. Prolonged catheterization due to anastomotic leakage was the most common complication. Age, preoperative clinical stage, NS procedure, and a pathological Gleason score were predictors for BCR. CONCLUSIONS: sRP was safe, feasible, and effective using either an open or robot-assisted approach, in experienced hands. Age, preoperative clinical stage, NS procedure, and pathological GS were linked with BCR after sRP.

Cardiovascular toxicities associated with immune checkpoint inhibitors: an observational, retrospective, pharmacovigilance study.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have substantially improved clinical outcomes in multiple cancer types and are increasingly being used in early disease settings and in combinations of different immunotherapies. However, ICIs can also cause severe or fatal immune-related adverse-events (irAEs). We aimed to identify and characterise cardiovascular irAEs that are significantly associated with ICIs. METHODS: In this observational, retrospective, pharmacovigilance study, we used VigiBase, WHO's global database of individual case safety reports, to compare cardiovascular adverse event reporting in patients who received ICIs (ICI subgroup) with this reporting in the full database. This study included all cardiovascular irAEs classified by group queries according to the Medical Dictionary for Regulatory Activities, between inception on Nov 14, 1967, and Jan 2, 2018. We evaluated the association between ICIs and cardiovascular adverse events using the reporting odds ratio (ROR) and the information component (IC). IC is an indicator value for disproportionate Bayesian reporting that compares observed and expected values to find associations between drugs and adverse events. IC025 is the lower end of the IC 95% credibility interval, and an IC025 value of more than zero is deemed significant. This study is registered with ClinicalTrials.gov, number NCT03387540. FINDINGS: We identified 31 321 adverse events reported in patients who received ICIs and 16 343 451 adverse events reported in patients treated with any drugs (full database) in VigiBase. Compared with the full database, ICI treatment was associated with higher reporting of myocarditis (5515 reports for the full database vs 122 for ICIs, ROR 11·21 [95% CI 9·36-13·43]; IC025 3·20), pericardial diseases (12 800 vs 95, 3·80 [3·08-4·62]; IC025 1·63), and vasculitis (33 289 vs 82, 1·56 [1·25-1·94]; IC025 0·03), including temporal arteritis (696 vs 18, 12·99 [8·12-20·77]; IC025 2·59) and polymyalgia rheumatica (1709 vs 16, 5·13 [3·13-8·40]; IC025 1·33). Pericardial diseases were reported more often in patients with lung cancer (49 [56%] of 87 patients), whereas myocarditis (42 [41%] of 103 patients) and vasculitis (42 [60%] of 70 patients) were more commonly reported in patients with melanoma (χ2 test for overall subgroup comparison, p<0·0001). Vision was impaired in five (28%) of 18 patients with temporal arteritis. Cardiovascular irAEs were severe in the majority of cases (>80%), with death occurring in 61 (50%) of 122 myocarditis cases, 20 (21%) of 95 pericardial disease cases, and five (6%) of 82 vasculitis cases (χ2 test for overall comparison between pericardial diseases, myocarditis, and vasculitis, p<0·0001). INTERPRETATION: Treatment with ICIs can lead to severe and disabling inflammatory cardiovascular irAEs soon after commencement of therapy. In addition to life-threatening myocarditis, these toxicities include pericardial diseases and temporal arteritis with a risk of blindness. These events should be considered in patient care and in combination clinical trial designs (ie, combinations of different immunotherapies as well as immunotherapies and chemotherapy). FUNDING: The Cancer Institut Thématique Multi-Organisme of the French National Alliance for Life and Health Sciences (AVIESAN) Plan Cancer 2014-2019; US National Cancer Institute, National Institutes of Health; the James C. Bradford Jr. Melanoma Fund; and the Melanoma Research Foundation.

Non-clear cell renal carcinomas: Review of new molecular insights and recent clinical data.

Non-clear cell renal cell carcinomas (nccRCC) represent a highly heterogeneous group of kidney tumors, consisting of the following subtypes: papillary carcinomas, chromophobe renal cell carcinoma, so-called unclassified carcinomas or aggressive uncommon carcinomas such as Bellini carcinoma, renal cell carcinoma (RCC) with ALK rearrangement or fumarate hydratase-deficient RCC. Although non-clear cell cancers account for only 15 to 30% of renal tumors, they are often misclassified and accurate diagnosis continues to be an issue in clinical practice. Current therapeutic strategy of metastatic nccRCC is based primarily on guidelines established for clear cell tumors, the most common subtype, however this approach remains poorly defined. To date, published clinical trials for all histological nccRCC subtypes have been collectively characterized into one group, in contrast to clear cell RCC, and given the small numbers of cases, the interpretation of study results continues to be challenging. This review summarizes the available literature for each nccRCC subtype and highlights the lack of supportive evidence from prospective clinical trials and retrospective studies. Future trials should evaluate treatment approaches which focus on a specific histological subtype and progress in treating nccRCC will be contingent on understanding the unique biology of their individual histologies.

Morbidity, perioperative outcomes and complications of robot-assisted radical prostatectomy in kidney transplant patients: A French multicentre study.

OBJECTIVE: Evaluate the safety, feasibility and efficiency of robot-assisted radical prostatectomy (RARP) in kidney transplant recipients, performed in high-volume French referral centres, and describe intra- and postoperative, oncological and functional outcomes. MATERIALS AND METHODS: A multicentre study was conducted on prospective RARP databases from 5 centres between 2008 and 2017. We retrospectively identified a first group (G1) of transplant patients. The following data were collected: age, body mass index, prostate-specific antigen, ISUP score, TNM stage, stratification according to d'Amico, renal function, renal disease, time between renal transplant and prostate cancer (PCa), operating time, bleeding, pre- and postoperative complications (according to Clavien). Group 1 data were matched with a second group (G2) of nontransplanted PTRA patients. RESULTS: A total of 321 patients were included (G1 N = 39 and G2 N = 282). The median operating time was 180 minutes (interquartile range 125-227) for G1 and 150 minutes (120-180) in G2 (P = 0.0623) and the median bleeding volume was 150 mL (150-400) and 250 mL (175-400), respectively (P = 0.1826). No grafts were damaged by RARP. Postoperative complication rate was significantly higher in G1: 51.2% vs. G2: 8.2% with a majority of minor complications (41%) according to Clavien Dindo (P < 0.001). Pathological assessment was as follows in G1: T2 = 28 (71.8%), T3 = 11 (28.2%), and G2: T2 = 206 (73.3%), T3 = 75 (26.7%) (P = 0.77). Postoperative ISUP scores were mainly grade 1: G1 = 14 (35.9%) vs. 99 (35.2%) in G2 and grade 2: respectively 18 (46.1%) 94 (33.5%). The rate of positive surgical margins was comparable in both groups: 13.2% for transplant patients vs. 18.1% (P = 0.65). Renal function was not significantly different at one year (P = 0.07). The median follow-up was 47.9 months (42.3; 52.5). CONCLUSION: RARP is conceivable to treat localized prostate cancer in kidney transplant recipients. This procedure does not appear to have any negative impact on graft renal function and cancer prognosis.

Neuroendocrine Carcinoma of the Urinary Bladder: A Large, Retrospective Study From the French Genito-Urinary Tumor Group.

BACKGROUND: Neuroendocrine carcinoma of the urinary bladder (NCUB) is rare, accounting for < 1% of bladder cancer cases, with scarce reported data available. MATERIALS AND METHODS: We retrospectively reviewed the data from patients with NCUB treated at French institutions. The objectives were to describe the patient characteristics, treatments received, and outcomes (ie, disease-free survival [DFS], progression-free survival, overall survival [OS]) and investigate the prognostic factors. RESULTS: From 1997 to 2017, we included 236 patients, 173 with early-stage NCUB and 63 with advanced-stage NCUB. For those with early-stage disease, the median DFS was better for the patients who had received cisplatin-based chemotherapy compared with carboplatin (hazard ratio [HR], 1.95; 95% confidence interval [CI], 1.1-3.46), with no difference found between the neoadjuvant and adjuvant settings (HR, 1.1; 95% CI, 0.61-1.97). The median OS was 36 months (95% CI, 29-43 months) for stage I and II, 26 months (95% CI, 18 months to not reached) for stage IIIA, 16 months (95% CI, 12-21 months) for stage IIIB. The HR for stage IIIB compared with stage I/II was 2.6 (95% CI, 1.5-4.4). The DFS at 6 months was associated with OS (HR, 7.8; 95% CI, 4.1-15.0). For patients with metastases at diagnosis who had received chemotherapy, the median progression-free survival was 9 months (95% CI, 8-11) for first-line cisplatin and 6 months (95% CI, 4-13 months) for carboplatin; the median OS was 13 months (95% CI, 9-15 months). A high-risk Bajorin score (HR, 11.5; 95% CI, 1.2-112.6) and the use of carboplatin (HR, 2.26; 95% CI, 1.03-4.96) were associated with worse outcomes. CONCLUSIONS: In early-stage disease, a shorter DFS was associated with worse OS, and the use of cisplatin was associated with better OS. For the patients with metastases at diagnosis, a high-risk Bajorin score and the use of carboplatin were associated with worse outcomes.

RECIST and CHOI criteria in the evaluation of tumor response in patients with metastatic colorectal cancer treated with regorafenib, a prospective multicenter study.

BACKGROUND: To evaluate the objective response rate (ORR) at 2 months of treatment with regorafenib according to RECIST 1.1, Choi, and modified Choi (mChoi) criteria in patients with metastatic colorectal cancer (mCRC). METHODS: Baseline and 2-month contrast-enhanced computed-tomography (CECT) scans of 55 patients with mCRC, prospectively enrolled in phase II TEXCAN trial, were centrally assessed. The primary endpoint was 2-month ORR by RECIST 1.1, Choi, and mChoi criteria. Final outcome was overall survival (OS). RESULTS: Of 55 patients included in this study (Intention-to-treat [ITT1] population), 35 had CECT at 2 months (ITT2 population). According to RECIST 1.1 criteria, 20 (57%) patients were SD and 15 were PD (43%) in the ITT2 population. According to Choi criteria, 18 (51%) patients were responders and 17 (48%) were non-responders. Median OS was 5.3 months (95% CI 3.7-8.6) in the ITT1 population and 8.9 months (95% CI 5.1-12.6) in the ITT2 population. In the ITT2 population, median OS was 16 months (95% CI 6.6-17.5) in SD patients (n = 20) and 4.6 months (95% CI 3.3-5.8) in PD patients (n = 15), according to RECIST 1.1 criteria (HR = 6.48). Median OS was 7.9 months (95% CI 4.2-17.5) in responders (n = 18) and 9.9 months (95% CI 3.7-NA) in non-responders (n = 17) according to Choi criteria (HR = 1.06). All patients except one were classified as non-responders with mChoi criteria. CONCLUSION: At 2 months, unlike RECIST 1.1, Choi and mChoi criteria could not identify mCRC patients with regorafenib survival benefit. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02699073.Registered March 4, 2016, Retrospectively registered.

Immunotherapy for cancer in people living with HIV: safety with an efficacy signal from the series in real life experience.

OBJECTIVE: To report efficacy and tolerance of nivolumab or pembrolizumab, PD-1 inhibitors, in people living with HIV (PLWHIV) and cancer. DESIGN: Series of PLWHIV cancer patients treated with anti-PD1 agents in real-life clinical practice. METHODS: From May 2014 to January 2019, 575 HIV-infected patients have been discussed in the French CANCERVIH national multidisciplinary board and included in the network database. Twenty-three patients were treated with immune checkpoint inhibitors in daily practice. We report the demographic characteristics, CD4 T-cell counts, HIV viral loads, safety and efficacy data of these 23 PLWHIV treated in routine practice with nivolumab or pembrolizumab for nonsmall cell lung cancer (n = 21), melanoma (n = 1) and head and neck cancer (n = 1) retrospectively collected from the database CANCERVIH network. The median CD4 T-cell count at treatment initiation was 370 cells/µl (IQR: 125-1485). HIV viral load was undetectable in all patients. RESULTS: As of 29 April 2019, with a median follow-up of 10.8 months (2.0-27.7), the median number of injections was 6 (IQR: 4-18). Only two grade 3 adverse reactions were reported (no toxic deaths or immune-related deaths). Among the 23 patients, a partial response was observed in five patients (22%), a stabilization for five (22%) and a progression in 13 (57%). Only one patient experienced a positive HIV viral load, but this occurred following ART interruption. CONCLUSION: Treatment with PD-1 inhibitors seems to have an efficacy signal and be well tolerated in PLWHIV, including impact on CD4 lymphocyte count and HIV load, that should be monitored during treatment course (regarding real-life experience).

HIV-associated cancers: the role of a unique multidisciplinary board to optimize patient's care behalf the CANCERVIH Group.

Since 1996, the life expectancy of people living with HIV (PLWHIV) has improved, while their risk of cancer is 2-3 times higher than in the general population. HIV-associated cancers remain a critical issue in this population and represent a particular care challenge due to the high risk of drug interactions and additive toxicity. The new standards of care with immunotherapy will also become a major issue for PLWHIV because of the potential impact on immunology and virology. Thus, the National Cancer Institute created the CANCERVIH national network in 2014 in France, enabling the establishment of a multidisciplinary national board of experts. This is an important first step that will help patients and health professionals provide optimal treatment to PLWHIV and prevent disparities. We hope that such a multidisciplinary council will make its voice heard in other countries and that this could be useful for patients with HIV-related cancers.

[HIV and cancer : What's new in 2017?] / Cancer et VIH : actualités 2017.

Since the era of combined antiretroviral therapy, life expectancy of people living with HIV has been improved and is associated with a change in causes of death. Cancer, both AIDS-defining or non-AIDS-defining cancers, has become the leading cause of death in people living with HIV associated with an increase in the incidence of some cancers compared to the general population. Epidemiology and the identification of risk factors is a crucial issue, particularly to determine the most appropriate prevention and screening strategies in this population. In the absence of dedicated clinical trials, the cancer management in these patients is based on general recommendations, with specific attention to comorbidities and drug interactions. In addition, the development of new innovative therapies such as immunotherapy with inhibitory antibodies of immune checkpoints receptor represents a hope for the patient care, both infected or not with HIV. In this context, the establishment of the national network CancerVIH makes sense, allowing the establishment of multi-disciplinary consultation meetings involving all the practitioners involved in the care of these patients with cancer, as well as the constitution of a national cohort and the promotion of dedicated trials, to improve and optimize the management for these patients.

[HIV-related malignancies: state of art]. / VIH et cancer : état des connaissances.

HIV infection is related to an increased risk of cancer compared with general population, both AIDS-defining cancers (Kaposi's sarcoma, non Hodgkin's lymphoma, invasive cervical cancer) and non-AIDS-defining cancers. Although the advent of the highly active antiretroviral therapy era has decreased the Kaposi's sarcoma and non-Hodgkin's lymphoma incidences, non-AIDS-defining malignancies, such as lung cancer, hepatocarcinoma, anal cancer and skin cancers, remain a major cause of morbidity and death in the HIV-infected population. The clinical presentation is often different between the infected and non-infected populations, often with a more advanced stage at diagnosis, a more aggressive pathology, and associated morbidities like immunosuppression, leading to poorer outcomes. Numerous studies have focused on HIV-related malignancies' treatment, however specific guidelines are still missing. Practitioners have to be careful with interactions between antiretroviral and antineoplastic drugs, particularly through the cytochrome P 450. Because of this, a national multidisciplinary approach, "Cancer and HIV, " was started in 2013 thanks to the National Institute of Cancer (INCa). The aim of this review is to present a scientific update about AIDS-and non-AIDS-defining malignancies, both in their clinical aspects and regarding their specific therapeutic management.