Survival after sequential neoadjuvant chemotherapy followed by trimodal treatment or radical cystectomy for muscle-invasive bladder cancer.

PURPOSE: to assess the respective outcomes of patients with localized muscle-invasive bladder cancer (MIBC) treated by either radical cystectomy (RC) or trimodal treatment (TMT) depending on pathological response to previous neoadjuvant chemotherapy (NAC) assessed on cystectomy specimen or post-NAC transurethral resection (TURB) specimen, respectively. PATIENT AND METHODS: We retrospectively included all consecutive patients treated in one academic center with cisplatin-based NAC followed by RC or TMT for cT2-3N0M0 MIBC between 2014 and 2021. Primary endpoint was metastasis-free survival (MFS) in both treatment groups and according to pathological response to NAC. Local recurrence-free survival and conservative management failure (metastasis-free bladder-intact survival) for patients treated with TMT were assessed. RESULTS: 104 patients were included, 26 treated with TMT and 78 with RC. The rate of complete pathological response was 47.4% in patients treated with RC (ypT0) and 66.7% in patients treated with TMT (ycT0). Median follow-up was 34.9 months. Four-year MFS was 72% in both treatment groups. Four-year MFS was 85% in both ypT0 RC patients and ycT0 TMT patients. ycT0 stage was associated with low rates of intravesical recurrence and conservative management failure. CONCLUSION: Patients with post-NAC ycT0 stage treated with TMT have favorable oncological outcomes similar to those of ypT0 patients treated with RC. Assessment of complete histological response with TURB after NAC may help in selecting the best candidates for bladder preservation with TMT.

Safety and efficacy of preoperative chemotherapy for muscle-invasive bladder cancer in elderly patients.

PURPOSE: This study aimed at describing the feasibility and oncological outcomes of standard cisplatin-based neoadjuvant chemotherapy (C-NAC) for muscle-invasive bladder cancer (MIBC) in patients aged ≥ 75 and assess the impact of baseline geriatric parameters. METHODS: This retrospective study included patients with stage cT2-4NanyM0 MIBC aged 75 and older treated with ≥ 1 cycle of C-NAC from 2011 to 2021 at a high-volume academic center. Primary outcome was overall survival (OS). Secondary outcomes were chemotherapy feasibility (administration of ≥ 4 cycles), safety, and pathological downstaging. RESULTS: Fifty-six patients were included. Median age was 79 (range 75-90). C-NAC regimen was ddMVAC in 41 patients and GC in 15. Seventy-three percent of patients received ≥ 4 cycles of C-NAC. Grade ≥ 3 toxicity was observed in 55% of patients. The febrile neutropenia rate was 7%. Thirty patients underwent cystectomy, and 13 underwent chemoradiotherapy. Three-year OS was 63%. Geriatric parameters polypharmacy, undernutrition, and age-adjusted Charlson comorbidity index ≥ 8 predicted worse OS. CONCLUSION: Standard-of-care C-NAC and local treatments are feasible in selected elderly MIBC patients, with efficacy and safety findings similar to that observed in pivotal trials with younger patients. The prognostic impact of geriatric parameters underlines the need for specialized evaluation before treatment initiation.

Phase II study of 131 I-metaiodobenzylguanidine with 5 days of topotecan for refractory or relapsed neuroblastoma: Results of the French study MIITOP.

PURPOSE: We report the results of the French multicentric phase II study MIITOP (NCT00960739), which evaluated tandem infusions of 131 I-metaiodobenzylguanidine (mIBG) and topotecan in children with relapsed/refractory metastatic neuroblastoma (NBL). METHODS: Patients received 131 I-mIBG on day 1, with intravenous topotecan daily on days 1-5. A second activity of 131 I-mIBG was given on day 21 to deliver a whole-body radiation dose of 4 Gy, combined with a second course of topotecan on days 21-25. Peripheral blood stem cells were infused on day 31. RESULTS: Thirty patients were enrolled from November 2008 to June 2015. Median age at diagnosis was 5.5 years (2-20). Twenty-one had very high-risk NBL (VHR-NBL), that is, stage 4 NBL at diagnosis or at relapse, with insufficient response (i.e., less than a partial response of metastases and more than three mIBG spots) after induction chemotherapy; nine had progressive metastatic relapse. Median Curie score at inclusion was 6 (1-26). Median number of prior lines of treatment was 3 (1-7). Objective response rate was 13% (95% confidence interval [CI]: 4-31) for the whole population, 19% for VHR-NBL, and 0% for progressive relapses. Immediate tolerance was good, with nonhematologic toxicity limited to grade-2 nausea/vomiting in eight patients. Two-year event-free survival was 17% (95% CI: 6-32). Among the 16 patients with VHR-NBL who had not received prior myeloablative busulfan-melphalan consolidation, 13 had at least stable disease after MIITOP; 11 subsequently received busulfan-melphalan; four of them were alive (median follow-up: 7 years). CONCLUSION: MIITOP showed acceptable tolerability in this heavily pretreated population and encouraging survival rates in VHR-NBL when followed by busulfan-melphalan.

Effectiveness of a multidisciplinary care program for the management of venous thromboembolism in cancer patients: a pilot study.

INTRODUCTION: Treatment of Venous thromboembolism (VTE) in cancer patients is challenging due to higher risk of VTE recurrence or bleeding under anticoagulants. We assessed the effectiveness of a dedicated "Allo-Thrombosis Cancer" multidisciplinary care program (AlloTC-MCP) that incorporated individualized care, regular follow-ups, telephone counselling, and a patient education program. METHODS AND MATERIALS: From September 2017 to October 2019, 100 consecutive cancer patients with new VTE onset were enrolled in this observational single-center prospective pilot study and received standard (control group, n = first 50 patients enrolled) or AlloTC-MCP care (n = next 50 patients enrolled) over a 6-month VTE treatment follow-up period. Primary end-point was the percentage of adherence to the International Clinical Practice Guidelines (ITAC-CPGs) at 6 (M6) month follow-up. RESULTS: Among the 100 patients with different cancer types (22% genitourinary, 19% breast, 16% gastrointestinal, 15% lymphoma, 11% lung and 17% others), 51 patients (61%) had metastatic disease and 31 (31%) received chemotherapy alone. Main baseline cancer and VTE clinical characteristics did not differ between the 2 groups. Adherence rates to ITAC-CPGs was significantly higher in the AlloTC-MCP group (100% (M0), 72% (M3) and 68% (M6)) compared with the control group (84% (M0), 8% (M3) and 16% (M6)). Quality of Life (QoL) was significantly improved in the AlloTC-MCP group 6 months after inclusion. CONCLUSION: The "AlloTC-MCP" was associated with improved adherence to ITAC-CPGs and merits further expansion.

Feasibility of Busulfan Melphalan and Stem Cell Rescue After 131I-MIBG and Topotecan Therapy for Refractory or Relapsed Metastatic Neuroblastoma: The French Experience.

High-risk neuroblastoma is characterized by poor long-term survival, especially for very high-risk (VHR) patients (poor response of metastases after induction therapy). The benefits of a tandem high-dose therapy and hematologic stem cell reinfusion (HSCR) have been shown in these patients. Further dose escalation will be limited by toxicity. It is thus important to evaluate the efficacy and tolerability of the addition of new agents such as I-MIBG (131Iode metaiodobenzylguanidine) to be combined with high-dose therapy in the consolidation phase. We report the feasibility of busulfan/melphalan (BuMel) after I-MIBG therapy with HSCR in patients with refractory or relapsed metastatic neuroblastoma. From November 2008 to March 2015, 9 patients received BuMel after I-MIBG therapy and topotecan. The main toxicity was digestive with only 1 patient developing grade 4 sinusoidal obstructive syndrome. Seven patients are alive at a median follow-up of 25 months. Among them, 2 are in ongoing complete remission and 1 in ongoing stable disease. These results suggest that BuMel with HSCR can be administered safely 2 months after I-MIBG therapy associated with topotecan for VHR patients. This strategy will be compared with tandem high-dose chemotherapy (thiotepa and busulfan-melphalan), followed by HSCR in the upcoming SIOPEN VHR Neuroblastoma Protocol.

Efficacy and safety of 153Sm-EDTMP as treatment of painful bone metastasis: a large single-center study.

PURPOSE: The purpose of this study is to assess the efficacy of 153Sm-EDTMP (Quadramet®) in a clinical setting. METHODS: We have conducted a retrospective study of all consecutive patients (pts) treated with 153Sm-EDTMP for painful bone metastases. At each visit (before and after treatment), four parameters were collected: (i) pain assessment according to the 10-step visual analogue scale (VAS), (ii) sleep disturbance related to pain, (iii) dose of analgesic medication, and (iv) answer to the following closed question "Do you think you obtained a benefit from treatment?" Success of treatment was defined by the combination of these four parameters. RESULTS: Three hundred seventy consecutive 153Sm-EDTMP treatments for painful bone metastases were given. Patients had the following primary tumors: breast carcinoma (153), prostate carcinoma (155), lung carcinoma (27), or other cancers (35). Fifty-eight percent of the patients had received previous external osseous radiotherapy. Ninety-seven percent of the patients were treated with concomitant analgesics and 61% were treated with diphosphonates. A clinical benefit was described in 55.0% of cases at D30. Treatment was more effective in cases of breast and prostate cancers compared with other types of primary cancers. Patients described a benefit at D30 in 62, 58, 6, and 38% of cases of breast, prostate, lung, and other cancers. The subjective efficacy was accompanied by a decrease in analgesic intake in 35.0% of cases. CONCLUSION: 153Sm-EDTMP therapy is an effective supportive treatment in patients who suffer from bone metastases, especially in patients with breast or prostate cancer.

[Medical treatment of metastatic kidney cancer: targeting the tumor micro-environment]. / Traitements médicaux des cancers du rein métastatiques : le ciblage de l'environnement tumoral.

Medical treatment of metastatic kidney cancer: targeting the tumor micro-environment. Metastatic kidney cancer has a poor prognosis. Progress has been made in recent years with the development of drugs targeting the tumor microenvironment, namely angiogenesis and immune infiltrate. First-line drugs inhibit neo-angiogenesis and target the vascular endothelial growth factor receptor. Nivolumab is an anti-PD1 human monoclonal antibody that, by binding to its target, interrupts binding with its ligand PD-L1 and thus restores T-cell activation and destroys the tumor cell. The median overall survival of patients is about 2 years.

Traitements médicaux des cancers du rein métastatiques : le ciblage de l'environnement tumoral. Le cancer du rein métastatique a un pronostic sombre. Des progrès ont néanmoins été réalisés au cours des dernières années avec le développement de médicaments ciblant le microenvironnement tumoral, à savoir la néo-angiogenèse et plus récemment l'infiltrat lymphocytaire. Les médicaments utilisés en première intention inhibent la néo-angiogenèse et ont pour cible le récepteur du vascular endothelial growth factor. Le nivolumab est un anticorps monoclonal humain anti-PD1 qui, en se fixant sur sa cible, interrompt la liaison avec son ligand PD-L1 et permet ainsi de restaurer l'activation du lymphocyte T et de détruire la cellule tumorale. La médiane de survie globale des patients est d'environ 2 ans.

An Unusual Late Recurrence of Wilms Tumor.

Wilms tumor is the most common renal tumor in children, and the 5-year survival rate is approximately 85%. The majority of relapses occur in the lung, tumor bed, and liver within 2 years of diagnosis. In this study, we describe an unusual late tumor recurrence that occurred 9.5 years after the primary diagnosis. The patient presented with a slow growing cervical lymphadenopathy. The recurrent tumor showed the same histologic features as the original tumor. The patient was treated with surgery and radiotherapy without chemotherapy. The patient remained disease free 15 months after treatment. The possible effect of treatment and other mechanisms of this late relapse are discussed.

Contribution of lymphoscintigraphy to intraoperative sentinel lymph node detection in early cervical cancer: Analysis of the prospective multicenter SENTICOL cohort.

PURPOSE: To evaluate the contribution of preoperative lymphoscintigraphy to intraoperative lymphatic mapping (ILM) in early cervical cancer METHODS: We conducted an ancillary analysis of the multicenter prospective SENTICOL study in early cervical cancer. Radiocolloid was injected intracervically on the day before (long protocol) or morning of (short protocol) surgery, lymphoscintigraphy was performed, and the results of a centralized image review were communicated to the surgeons. ILM was performed on combined radioactivity/patent blue detection. Sentinel lymph nodes (SLNs) were electively sampled before routine bilateral pelvic lymphadenectomy by laparoscopy. RESULTS: Of 139 patients in the modified intention-to-diagnose analysis, 114 had centrally reviewed lymphoscintigrams, which showed 352 SLNs in 100 patients. Lymphoscintigraphy and ILM detection rates were 87.8% and 97.8%, respectively. Agreement between lymphoscintigraphy and ILM was low for the number of SLNs (κ=0.23; -0.04; 0.49) and bilateral SLNs (κ=0.36; 0.2; 0.52). No patient without SLNs by ILM had SLNs by lymphoscintigraphy. Lymphoscintigraphy identified substantial proportions of unusual drainage pathways. No patients with metastatic nodes had SLNs by lymphoscintigraphy but not by ILM in the relevant territory. In 1 of the 2 patients with false-negative SLN results, SLNs were bilateral by lymphoscintigraphy and unilateral by ILM. CONCLUSION: Although the detection rate was lower by lymphoscintigraphy than by ILM, the substantial proportions of SLNs in unusual territories provided valuable guidance for the surgical exploration. Awareness of the limited agreement between lymphoscintigraphic and surgical detection might help surgeons decrease the false-negative rate.

[Management of metastatic bladder cancer]. / Prise en charge des tumeurs de vessie métastatiques.

The management of patients with metastatic bladder cancer is mainly based on cytotoxic chemotherapy. The reference molecule is cisplatin. In 2014, first-line regimens include gemcitabine and cisplatin (GC protocol) or methotrexate, vinblastine, and cisplatin doxorubicin (MVAC protocol). When cisplatin is contra-indicated, another platinum Salt, carboplatin, is used in combination with gemcitabine. Vinflunine is the only molecule to have obtained a marketing approval for patients who failed first-line chemotherapy including a platinum salt. The overall prognosis of patients remains dismal, since the median overall survival is 12 to 14 months for patients being treated with cisplatin, whereas it is less than 1 year for patients receiving carboplatin. The identification of new effective drugs is a major challenge for the coming years.

[Chemotherapy in castrate-resistant metastatic prostate cancer]. / Chimiothérapie dans le cancer de la prostate métastatique résistant a la castration.

Chemotherapy is currently used in metastatic, castrate-resistant prostate cancer. The key drugs are docetaxel and cabazitaxel since two large randomized trials have shown a survival benefit for docetaxel in first-line and cabazitaxel in second-line as compared to mitoxantrone during the last decade. Docetaxel and cabazitaxel belong to the taxane family and inhibit the polymerization dynamics of microtubules during the cell cycle. These are delivered every 3 weeks in an outpatient setting. The main side effects are neutropenia, alopecia, mucositis, diarrhea and peripheral neuropathy. The prophylactic use of hematopoietic growth factor (G-CSF) in patients older than 70 years reduces the risk of febrile neutropenia. Chemotherapy is primarily used in patients with symptomatic or rapidly progressive disease.

Nodal-staging surgery for locally advanced cervical cancer in the era of PET.

Chemoradiation therapy is deemed the standard treatment by many North American and European teams for treatment of locally advanced cervical cancer. The prevalence of para-aortic nodal metastasis in these tumours is 10-25%. PET (with or without CT) is the most accurate imaging modality to assess extrapelvic disease in such tumours. The true-positive rate of PET is high, suggesting that surgical staging is not necessary if uptake takes place in the para-aortic region. Nevertheless, false-negative results (in the para-aortic region) have been recorded in 12% of patients, rising to 22% in those with uptake during PET of the pelvic nodes. In such situations, laparoscopic surgical para-aortic staging still has an important role for detection of patients with occult para-aortic spread misdiagnosed on PET or PET-CT, allowing optimisation of treatment (extension of radiation therapy fields to include the para-aortic area). Complications of the laparoscopic procedure were noted in 0-7% of patients. Survival of individuals (missed by PET) with para-aortic nodal metastasis of 5 mm or less (and managed by extended field chemoradiation therapy) seems to be similar to survival of those without para-aortic spread, suggesting a positive therapeutic effect of the addition of staging surgery. Nevertheless, the effect on survival of potential delay of chemoradiation owing to use of PET and staging surgery, and acute and late complications of surgery followed by chemoradiation therapy (particularly in case of extended field chemoradiation to para-aortic area), need to be studied.

Short-course treatment after complete response to pembrolizumab in metastatic urothelial bladder cancer: a case series.

Background: The optimal duration of treatment for metastatic patients who achieve a complete response with immune checkpoint inhibitors is unknown. Methods: The outcome for six metastatic bladder cancer patients who received short course of pembrolizumab is reported. Results: A median number of seven cycles of pembrolizumab was given. After a median follow-up of 38 months, progressive disease was confirmed in three patients. All patients relapsed in lymph nodes and underwent pembrolizumab rechallenge: one achieved a complete response, another a partial response. Conclusion: Our case series paves the way for discontinuation of pembrolizumab in patients who achieve a complete response since three out of six patients remain free of disease after 3-year follow-up. Prospective studies are required to confirm our results.

The rise of immunotherapy in oncology has provided significant gains in survival of metastatic patients. However, questions persist about the optimal use of immune checkpoint inhibitors. For now, treatment is supposed to be delivered until progression of disease. We report a case series of six patients who received a short course of treatment after achieving a complete response. Three of them remained free of recurrence after a median follow-up of 3 years. Our results suggest that a stop-and-go strategy might be appropriate for some patients, thereby sparing the potential toxicities associated with prolonged exposure.

Predictive value of neoadjuvant chemotherapy failure in breast cancer using FDG-PET after the first course.

The aim of this study was to prospectively evaluate the predictive value of (18)F-fluorodeoxyglucose-positron emission tomography (FDG-PET) to detect the absence of pathological response to preoperative chemotherapy in patients (pts) with breast cancer. 63 consecutive pts with non-metastatic, non-inflammatory breast cancer, eligible for neoadjuvant chemotherapy (3 FEC 100 followed by 3 Docetaxel) were enrolled. FDG-PET was performed just before the first as well as before the second course. Metabolic activity (tumour FDG uptake) was measured by standardised uptake value (SUV(max)). Pts were classified as non-responders (NR) when the decrease of SUV(max) in the primary tumour was less than 15% at the time of the second PET (EORTC 1999 criteria). The metabolic response in FDG-PET was correlated with WHO criteria (clinical evaluation and ultrasound and/or mammography) evaluated after three cycles, pathological complete response (pCR) after surgery (according to Sataloff classification) and 4-year relapse-free survival (RFS). The mean SUV(max) decrease according to histological response was -52 ± 21% in case of pCR (Sataloff A) and 25 ± 34% in other cases (Sataloff B + C + D). Out of the 16 pts with no PET response (SUV decrease less than 15%), only one had a clinical response after the third cycle, and no pCR was observed. The 4-year RFS rate was significantly longer for metabolic responders than for NR (respectively, 85 vs. 44%; P = 0.01). This prospective study shows that a decrease in the SUV of less than 15% after the first chemotherapy course is a very potent predictor for failure of neoadjuvant chemotherapy, especially of pCR. It is interesting to note that this was shown despite the fact that the chemotherapy regimen was changed after the third course.

[Intrathecal methotrexate chemotherapy for leptomeningeal carcinomatosis]. / Meningitis carcinomatosa kezelése intrathecalis methotrexat-kemoterápiával.

Lung and breast cancer can give meningeal metastases. Clinical manifestations of leptomeningeal carcinomatosis include all forms of defect of the central nervous system depending on the localization of carcinomatous foci. Diagnosis is based on the detection of carcinomatous cells by the cytological examination of the cerebrospinal fluid. Without treatment the prognosis is limited to only some weeks or months. In case the meningeal carcinomatosis is related to breast cancer, intrathecal methotrexate chemotherapy may allow a significant survival benefit and improve the quality of life in about half of the patients.

Disseminated Intravascular Coagulation with Enhanced Fibrinolysis Caused by Heart Metastasis of Bladder Urothelial Carcinoma.

Heart metastases from urothelial carcinoma of the bladder have rarely been reported in the literature. We present a case complicated by symptomatic disseminated intravascular coagulation in a 67-year-old woman. A rapid and sustained recovery from hemostatic troubles was obtained following fibrinogen supplementation combined with second-line paclitaxel chemotherapy.

Neoadjuvant nivolumab for patients with resectable HPV-positive and HPV-negative squamous cell carcinomas of the head and neck in the CheckMate 358 trial.

BACKGROUND: Head and neck squamous cell carcinomas (HNSCCs) are common malignancies caused by carcinogens, including tobacco and alcohol, or infection with human papillomavirus (HPV). Immune checkpoint inhibitors targeting the programmed cell death 1 (PD-1) pathway are effective against unresectable recurrent/metastatic HNSCC. Here, we explored the safety and efficacy of anti-PD-1 therapy in at-risk resectable HPV-positive and HPV-negative HNSCC in the neoadjuvant setting. METHODS: The phase I/II CheckMate 358 trial in virus-associated cancers assessed neoadjuvant nivolumab in patients with previously untreated, resectable HPV-positive or HPV-negative HNSCC. Patients received nivolumab 240 mg intravenously on days 1 and 15, with surgery planned by day 29. Safety/tolerability (primary endpoint) was assessed by monitoring adverse events (AEs) and surgical delays. Radiographic response was measured before surgery using RECIST v1.1, adapted for a single post-nivolumab evaluation. Pathologic specimens were examined for treatment response using immune-based criteria. RESULTS: From November 2015 to December 2017, 52 patients with AJCC (seventh edition) stage III-IV resectable HNSCC received neoadjuvant nivolumab (26 HPV-positive, 26 HPV-negative). Any-grade treatment-related AEs (TRAEs) occurred in 19 patients (73.1%) and 14 patients (53.8%) in the HPV-positive and HPV-negative cohorts, respectively; grade 3-4 TRAEs occurred in five (19.2%) and three patients (11.5%), respectively. No patient had a protocol-defined TRAE-related surgical delay (>4 weeks). Thirty-eight patients were reported as undergoing complete surgical resection, 10 had a planned post-nivolumab biopsy instead of definitive surgery due to a protocol misinterpretation, and four did not undergo surgery or biopsy, including two with tumor progression. Radiographic response rates in 49 evaluable patients were 12.0% and 8.3% in the HPV-positive and HPV-negative cohorts, respectively. There were no complete pathologic responses by site or central review in operated patients. Among 17 centrally evaluable HPV-positive tumors, one (5.9%) achieved major pathological response and three (17.6%) achieved partial pathologic response (pPR); among 17 centrally evaluable HPV-negative tumors, one (5.9%) achieved pPR. CONCLUSIONS: Neoadjuvant nivolumab was generally safe and induced pathologic regressions in HPV-positive (23.5%) and HPV-negative (5.9%) tumors. Combinatorial neoadjuvant treatment regimens, and continued postoperative therapy for high-risk tumors, are warranted in future trials to enhance the efficacy of this approach. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT02488759; https://clinicaltrials.gov/ct2/show/NCT02488759.

Multimodal strategy for the management of sphenoid osteoradionecrosis: Preliminary results.

OBJECTIVE: Osteoradionecrosis (ORN) of the sphenoid is a rare but potentially lethal complication that can occur after irradiation of nasopharyngeal and clival malignancies. The objective of this study was to describe a multimodal treatment strategy tailored to the clinical signs and to the radiological extent of the disease, and to report on its preliminary results. METHODS: Retrospective monocentric study at a tertiary skull base center. Patients treated for a sphenoid ORN from January 2014 to August 2018 were identified and charts were retrospectively reviewed for demographics, histologic tumor type, previous treatments of the tumor, clinical signs at presentation, radiological data, treatment, and outcomes. Sphenoid ORN was treated by a combination of medical therapy, endovascular treatment, and/or surgery. The use of each of these therapeutic modalities was based on the extent of ORN and on the presenting signs. RESULTS: Seven patients were included: four patients underwent endovascular treatment with occlusion of the internal carotid artery, five patients underwent surgical debridement, and covering of the exposed bone by a local flap, seven patients received antibiotics (in combination with pentoxyphilline, tocopherol, and clodronate in one case). Three patients died after progression of the ORN. The global survival rate was 57% (4/7) with a mean follow-up of 24 months. In one case, ORN was treated successfully by medical treatment only, with a combination of antibiotics, pentoxyphilline, tocopherol, and clodronate. CONCLUSION: This retrospective study describes the results of a management strategy adapted to the extent of the disease in sphenoid ORN and based on medical therapy only, or on a combination of medical therapy, interventional radiology, and/or surgery. LEVEL OF EVIDENCE: 4.

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.