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Abstract: Objectives: As a consequence of under-representation of elderly patients in clinical trials, the recommended dose of chemotherapy is often based on results observed in younger patients. We designed a risk-adapted, dose escalation study of weekly docetaxel in the first-line treatment of elderly patients with cancer in order to determine the optimal dose according to age, comorbidity and functional status. Patients and Methods: Sixty-eight patients aged 70 or more were stratified into three risk groups according to a combination of age, performance status, and comorbidity. The study was conducted using a standard phase I design with sequential cohorts of patients receiving docetaxel at increasing doses in each risk group. Results: The maximum tolerated dose was not reached in the intermediate-risk group and was 45mg/m2/week in the high-risk group. Because of a slow recruitment rate, it was not possible to conclude the trial in the good-risk category. Neutropenia, asthenia and diarrhea were the most frequently encountered severe toxicities. Conclusions: Docetaxel can be used at a dose of 40mg/m2/week as a first-line treatment for elderly patients with locally advanced or metastatic cancer without excessive toxicity. The risk groups defined in the study are not able to accurately distinguish between subgroups of patients with divergent toxicity profiles. [Copyright &y& Elsevier]

Prognostic factors in the setting of treated metastatic renal cell carcinoma (mRCC) can theoretically predict drug response, progression-free survival or overall survival. These factors are potentially useful for informing patients and for tailoring medical treatment according to risk assessment. Prognostic factors were well defined in the era of immunotherapy. Since 2006, tyrosine kinase inhibitors and anti-angiogenic drugs have revolutionized the treatment of mRCC by improving progression-free survival and overall survival. Physicians now need new predictive tools adapted to targeted therapies. The aim of our study was to review the current knowledge about prognostic factors in mRCC by focusing on anatomical, clinical, biological, histological, radiological and molecular parameters. The most recent integrated prognostic models will be reviewed as well. [ABSTRACT FROM AUTHOR]

Background: There is no standard second-line chemotherapy for patients who relapse with advanced urothelial carcinoma. A GETUG phase II clinical trial was designed to evaluate the response rate and the palliative clinical benefit of weekly paclitaxel. Patients and Methods: Paclitaxel (80 mg/m2, 1 hour) was administered on day 1, 8, and 15 (28-day course) to 45 patients. The primary endpoint was disease control rate (objective response and stable disease). Response rate was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) criteria; quality of life (QOL) assessment used FACT-B1 and FACT-Taxane questionnaires. Results: Characteristics of the patients were: M/F, 36/9; mean age, 64 years; performance status (PS) 0-1, 82%; metastatic disease, 93%; gemcitabine/platinum first-line chemotherapy, 89%; median number of cycles, 2. Grade 3/4 toxicity was uncommon. The disease control rate was 47%. One patient achieved a complete response, 3 a partial response (objective response, 9%) and 17 (38%) a stable disease. Median time to progression or death were 3 and 7 months. Among the 21 patients with controlled disease, 10% displayed QOL improvement, and 14% decreased their analgesic consumption. Conclusion: Weekly paclitaxel is associated with limited objective response but a high rate of stabilization; QOL assessment indicates that a small group of patients might experience a clinical benefit. [ABSTRACT FROM AUTHOR]

The development of targeted molecules in renal carcinogenesis changed the therapeutic approaches of treatment for metastatic clear cell renal cell carcinoma. Four available drugs are currently available, i.e. bevacizumab, sunitinib, sorafenib and temsirolimus, but other molecules and combined therapy are under investigation. In this review we assess published reports of these targeted therapies and discuss the novel promising molecules targeting vascular endothelial growth factor and its receptors, the mammalian target of rapamycin and epithelial growth factor cascade. [ABSTRACT FROM AUTHOR]

Objectives: Our objective was to explore the pathologic components of residual masses after primary chemotherapy in patients with metastatic nonseminomatous germ cell tumors. Methods: A multicenter retrospective study was conducted of 71 patients with thoracic residual masses (39 patients had bilateral lung metastasis) after first-line cisplatin-based chemotherapy for disseminated nonseminomatous germ cell tumors. Among the 71 patients, 52 also had a retroperitoneal lymph node dissection. Results: Pathologic findings in postchemotherapy residual masses included complete necrosis, teratoma, and viable cancer in 31%, 55%, and 14% of patients, respectively. Discordant pathologic findings were evidenced between retroperitoneal lymph node and thoracic (lung or mediastinal lymph nodes) residual masses in 27% of patients. When a bilateral pulmonary resection was performed, only 2 (5%) of 39 patients had discordant histologic findings between the two lungs. Among patients who had necrosis only in residual masses from their first lung (n = 20), 19 (95%) also had necrosis only in contralateral lesions. A single patient had necrosis only in the first lung and some teratoma in the contralateral lung. Conclusions: This report shows a high rate (95%) of pathologic concordance between the two lungs. Avoiding contralateral lung surgery could therefore be considered when complete necrosis is found in the first lung after induction chemotherapy for nonseminomatous germ cell tumor. [Copyright &y& Elsevier]

To present an update on anti-angiogenic drugs in the treatment of metastatic renal cell carcinoma. A better understanding of molecular pathways that are involved in clear cell carcinomas has led to the development of multiple targeted therapies with significant clinical benefits. Two tyrosine kinase inhibitors targeting the vascular endothelial growth factor (VEGF) receptor have been shown to improve the progression-free survival of patients in first-line (Sunitinib vs. interferon-α) or second-line treatment (Sorafenib vs. placebo). Temsirolimus, an agent that inhibits the serine–threonine kinase activity of the mammalian target of rapamycin, offers better overall survival than interferon in patients with poor-risk characteristics. Finally, Bevacizumab, which is an antibody directed against VEGF, in association with IFN is providing substantial response rates and increased progression-free survival compared to IFN alone. Four major drugs or regimens with proven efficacy are now available in first and second line therapy in metastatic renal cell carcinoma (mRCC). Further studies are needed to determine the optimal combinations of these agents in metastatic disease and to assess their impact in the adjuvant setting. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: To report the high incidence of intracerebral hemorrhage (ICH) in patients with metastatic renal cell carcinoma (RCC) treated with the tyrosine kinase inhibitors targeting the vascular endothelial growth factor receptor (VEGFR). Methods and results: Between October 2005 and December 2006, 67 patients with metastatic RCC were treated with sorafenib or sunitinib at the Montpellier Cancer Center in compassionate access programs. The medical records of five (7%) patients who died of ICH during therapy were reviewed retrospectively. Four of them had known brain metastases. Previous radiation therapy had been indicated in two patients. Two patients had a history of hypertension. Death from ICH occurred in the first 2 wk following the onset of treatment. Three other patients with brain metastases who received sorafenib or sunitinib during the same period did not experience ICH. Conclusions: The frequency of fatal ICH in RCC patients with brain metastases treated with tyrosine kinase inhibitors targeting the VEGFR seems high. Prospective clinical trials will be necessary for assessing the true incidence and predictive factors related to this toxicity. [Copyright &y& Elsevier]

Purpose: A link between neuroendocrine cell differentiation and resistance to androgen deprivation has been observed in prostate cancer, suggesting the possible efficacy of specific treatments. We assessed the efficacy and toxicity of a chemotherapy regimen combining docetaxel and cisplatin in men with androgen independent prostatic adenocarcinoma and circulating neuroendocrine markers. Materials and Methods: A total of 41 patients were treated with a combination of 75 mg/m2 docetaxel and 75 mg/m2 cisplatin every 3 weeks for a maximum of 6 cycles. The primary study end point was the neuroendocrine response rate, defined as a decrease in neuron specific enolase and/or chromogranin A to 50% or greater of the supranormal baseline serum value. Median followup was 40 months. Results: A median of 6 cycles per patient was delivered. A neuroendocrine response was observed in 13 patients (33%). The median response duration was 4 months (range 2 to 10). The prostate specific antigen response rate was 48%. A clinical benefit was observed in 45% of patients who required analgesics at study entry. The objective response rate was 41% in 29 patients with measurable metastases. Five patients had to stop therapy due to toxicity. The main side effects were cumulative asthenia and sensitive neuropathy. Median survival was 12 months (range 1 to 38). Conclusions: Regarding the disappointing efficacy and significant toxicity observed in this study, the combination of docetaxel and cisplatin cannot be recommended in daily practice. Further studies are necessary to determine whether patients with circulating neuroendocrine markers require specific therapeutic approaches. [Copyright &y& Elsevier]

Purpose: Collecting duct carcinoma of the kidney is a rare and aggressive neoplasm of the distal collecting tubules for which there is no established treatment. Since the histology of collecting duct carcinoma is similar to that of urothelial carcinoma, the standard chemotherapy regimen defined by a gemcitabine and platinum salts combination was prospectively investigated in patients with metastatic collecting duct carcinoma. Materials and Methods: A total of 23 patients with metastatic collecting duct carcinoma with no prior systemic chemotherapy were treated with 1,250 mg/m2 gemcitabine on days 1 and 8 plus 70 mg/m2 cisplatin or carboplatin (AUC 5) in patients with renal insufficiency on day 1. The drugs were repeated every 21 days for 6 cycles according to toxicity and efficacy. The objective response rate was the primary end point. Results: There were 1 complete and 5 partial responses for an objective response rate of 26% (95% CI 8 to 44). Median progression-free and overall survival was 7.1 (95% CI 3 to 11.3) and 10.5 months (95% CI 3.8 to 17.1), respectively. Toxicity was mainly hematological with grade 3–4 neutropenia and thrombocytopenia in 52% and 43% of patients, respectively. The severity of granulocytopenia and the number of metastatic sites were associated with overall survival on univariate and multivariate analyses. Conclusions: To our knowledge this is the first prospective, multicenter, phase II study showing that the platinum salts combination is an active and safe regimen as first line treatment in patients with metastatic collecting duct carcinoma. This platinum based chemotherapy should be considered the standard regimen in these patients. [Copyright &y& Elsevier]

OBJECTIVE To assess the clinical characteristics and outcome of patients with liver metastases in prostate carcinoma. PATIENTS AND METHODS From January 1995 to December 2005, 345 patients with metastatic prostate cancer were prospectively recorded in the database of the Montpellier Cancer Centre, France. The clinical characteristics and outcome of 28 patients who developed liver metastases during the course of the disease were analysed. RESULTS Six patients had liver metastases as the first site of metastatic disease, and for one of them, liver was the only metastatic site. All but one patient had hormone-refractory disease. Serum measurement of neuroendocrine markers showed increased levels of chromogranin A and neurone-specific enolase in 84% and 44% of patients, respectively. Six patients had a pathological analysis; there were two different histological patterns in liver biopsies, i.e. four were adenocarcinomas with a moderate (one patient) or poor (three) differentiation and two were neuroendocrine carcinomas. Three patients had no treatment because of a poor performance status. One patient had hormone therapy for synchronous liver metastases at diagnosis as the first-line treatment; other patients were treated with chemotherapy. The median (range) overall survival was 6 (1–27) months; the median survival of patients for whom liver was part of the initial metastatic pattern was 14 months. CONCLUSION Liver metastases are not very rare but appear to be a rather late event in the course of the disease. They are frequently associated with neuroendocrine characteristics. [ABSTRACT FROM AUTHOR]

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Summary: Introduction: Radiation recall is an inflammatory skin reaction at a previously irradiated field subsequent to the administration of a variety of pharmacologic agents. Although skin has been the major site of radiation recall toxicity, instances involving other organ have been reported. Materials and methods: Data for this review were identified by searches of Medline and Cancerlit. The search terms “radiation”, “recall”, and “toxicity” were used. References identified from within retrieved articles were also used. There was no limitation on year of publication and no abstract forms were included. Only articles published in English were taken into consideration. Results: Idiosyncratic drug hypersensitivity phenomenon is a recent hypothesis which correlates best with the available facts at this moment. The phenomenon may occur days to years after radiotherapy has been completed. The majority of the drugs commonly used in cancer therapy have been involved in the radiation recall phenomenon. A mixed non-specific inflammatory infiltrate seems to be the common histopathologic criteria in previous published reports. Universally, corticosteroids or the use of non-steroidal anti-inflammatory agents, in conjunction with withdrawal of the offending agent, produce prompt improvement. Conclusion: We propose to collect all future radiation recall phenomenon in a Rare Cancer Network database in order to augment our understanding of this rare reaction. [Copyright &y& Elsevier]

In this article, we describe the case of 4 brothers, 2 of which had primary mediastinal nonseminomatous germ cell tumors (PMNSGCT), while the other 2 had benign mediastinal disease. We discuss the relationship between these diseases of the mediastinum and the thymic microenvironment. Additionally, we suggest that a genetic predisposition for germ-cell tumors (GCT) may be involved since the parents were relatives. [Copyright &y& Elsevier]

Purpose. The objective of the present study was to characterize the population pharmacokinetics of melphalan infused over a 24-h period in patients with advanced malignancies. Methods. Enrolled in the study were 64 patients (144 courses). The population pharmacokinetic analysis was performed using NONMEM through the graphical interface Visual-NM. Population characteristics were computed from an initial group of 43 patients (99 courses), and 21 additional patients (45 courses) were used for model validation. With the use of a one-compartment model, the influence of demographic and biological characteristics was examined. The basic parameters were total clearance (CL) and volume of distribution (V). The interoccasion variability was taken into account in the model. The drug exposure was estimated for each patient and correlated with markers of efficacy and toxicity. Results. Data analysis was performed using a three-step approach. In step 2, a close relationship was found between creatinine clearance, gender and melphalan CL. The inclusion of this second stage model significantly improved the fit. Melphalan CL was higher in male patients (14.3±4.5 l/h per m2) than in female patients (12.3±4.5 l/h per m2). CL was also reduced somewhat in patients with decreased creatinine clearance. Large interindividual variability in pharmacokinetic parameters occurred (CL varied from 4.4 to 30.6 l/h per m2). The percentage intrapatient variability in clearance between courses was 25.4%. For determining melphalan AUC in clinical routine from one sample drawn at steady state, Bayesian methodology allowed a more accurate estimation of CL than the classical formula. Neutropenia and thrombocytopenia were the main haematological toxicities encountered; grade 4 was observed in 34 and 22 courses over a total of 144 courses, respectively. No significant relationship between AUC and haematological toxicity was found. In patients with prostatic cancer a weak relationship was observed between the decrease in PSA levels and AUC (P=0.0457), while in patients with ovarian cancer no relationship was found between AUC and CA125 levels. Conclusion. The population pharmacokinetic approach developed in this study should allow dosage to be individualized in order to decrease toxicity while maintaining good efficacy. [ABSTRACT FROM AUTHOR]

Among patients suffering from nonseminomatous germ-cell tumor, with a poor prognosis, a subset underwent respiratory failure and died very early in the course of their treatment. Between 1982 and 1989, 11 out of 56 such patients (20%) died within the first 5 weeks of chemotherapy. The clinical, radiological, biological and infectious characteristics of these patients were analyzed. Nine patients had extensive pulmonary metastases and the 2 others presented a bulky mediastinal mass with pleural effusion. All patients experienced acute respiratory distress during chemotherapy and underwent mechanical ventilation. All patients were febrile, and septicemia was documented in 7 cases. WHO grade 4 and grade 1-2 renal toxicities occurred in 3 and 4 patients respectively. There was no tumor lysis syndrome. All patients died within 35 days from the start of therapy; 4 were autopsied. These 11 patients represent a clinical entity, having what we called super-high-risk germ cell tumors. Early death is related to pulmonary distress within the first 5 weeks of therapy. The origin of the pulmonary distress is multifactorial: bulky disease of the chest, infection, and interstitial fibrosis. Immediate full-dose standard chemotherapy in association with intensive supportive care is recommended in the management of these patients. [ABSTRACT FROM AUTHOR]

Acute tumor lysis syndrome (ATLS) is a well-known adverse event described after effective chemotherapy for extensive, highly proliferative, and chemosensitive tumors. While its occurrence with hematological malignancies is frequently described, there have been scattered case reports documenting ATLS in solid tumors. However, such events have not been reported in poor-risk germ cell tumors. We reviewed retrospectively 46 cases of such tumors treated in our department between 1988 and 1993 by aggressive cisplatin-based chemotherapy. All patients received systematically 6 l/24 h hydration according to the cisplatin- protocol administration. Blood chemistry data for potassium, phosphorus, calcium, alkaline reserve, uric acid, creatinine and lactate dehydrogenase were obtained before treatment and during the 7 days of the induction chemotherapy. No metabolic abnormalities suggestive of ATLS were observed. Nevertheless, 2 patients with bulky disease of the chest experienced early death from respiratory distress complicated by multiorgan failure. ATLS seems to be an unlikely event in poor-risk germ cell tumors and therefore special prophylactic therapy may be unnecessary. [ABSTRACT FROM AUTHOR]

1. SEMITEP assessed whether men with good-prognosis metastatic seminoma could be treated with fewer cycles of chemotherapy based on interim fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT). 2. A majority of patients could benefit from excellent outcomes with limited chemotherapy using early FDG-PET/CT as an indicator of response. In metastatic seminoma, a strategy is needed for selecting patients for less intensive chemotherapy, to limit toxicities. To assess whether men with good-prognosis metastatic seminoma could be treated with two cycles of etoposide-cisplatin (EP) followed by only one cycle of carboplatin (CARBO) based on negative interim fluorodeoxyglucose positron emission tomography (FDG-PET)/computed tomography (CT). A nonrandomised, multicentre, phase 2 trial was conducted (NCT01887340). All patients with baseline-positive FDG-PET/CT received EP for two cycles. After completing the first two cycles, the patients underwent a second FDG-PET/CT to assess the response. Patients with positive FDG-PET/CT proceeded directly to two additional EP cycles; those who achieved FDG-PET/CT negativity received one cycle of CARBO. The proportion of patients with negative interim FDG-PET/CT who received carboplatin was determined. Between 2013 and 2017, 102 patients were enrolled. After the first two EP cycles, FDG-PET/CT was available in 98 patients. Overall, 67 patients (68.4%; 95% confidence interval [CI]: 58.2–77.4) had negative FDG-PET/CT and proceeded to a single CARBO cycle. Twenty-seven patients (27.6%; 95% CI: 19.0–37.5) had positive FDG-PET/CT after two EP cycles. The 3-yr progression-free survival rate was 90.0% (95% CI: 74.4–96.5) in the EP group and 90.8% (95% CI: 81.4–95.7) in the CARBO group. The cumulative incidences of peripheral neuropathy and ototoxicity were significantly higher in the EP group. Omission of two cycles of EP based on negative FDG-PET/CT after two cycles of chemotherapy appears to be feasible. However, the absence of consensus criteria for FDG-PET/CT interpretation and the short follow-up need additional studies. This strategy does not warrant routine integration yet. Men with good-prognosis metastatic seminoma were treated with fewer cycles of chemotherapy based on interim fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT). Omission of two cycles of chemotherapy based on negative FDG-PET/CT after two initial cycles appears to be feasible, thereby limiting the burden of treatment and toxicity. [ABSTRACT FROM AUTHOR]

Flexible parametric survival models with cure and milestone survival complement the Cox model, and help clinicians and regulators evaluate the benefit-risk ratios of new therapeutics. The flexible parametric survival model with cure facilitates patients' understanding of risk information. The Keynote-045 trial illustrates that the long-term benefit (LTB) of treatment does not always translate to improved progression-free survival (PFS). Milestone survival and flexible parametric survival model with cure (FPCM) have been proposed as complementary statistical approaches to more comprehensively evaluate LTBs of treatments. The current study compares milestone survival and FPCM analyses to evaluate treatment effects of immune checkpoint inhibitor (ICI) phase III trials. Individual patient data, from initial and follow-up analyses of Keynote-045 (urothelial cancer) and Checkmate-214 (advanced renal cell carcinoma), were reconstructed for PFS. Each trial was reanalyzed using the Cox proportional hazard regression and two complementary methods (milestone survival and FPCM) to estimate treatment impact on the LTB. For each trial, there was evidence of nonproportional hazards. For the long-term analysis of the Keynote-045 trial, FPCM identified a time-dependent effect on PFS, but the Cox model found no statistical difference in PFS (hazard ratio, 0.90; 95% confidence interval, 0.75–1.08). Milestone survival and FPCM identified improvements in the LTB fractions. This was consistent with the results from the reanalysis of Keynote-045, based on the shorter follow-up, although the LTB fraction was not retained. The increase in PFS in Checkmate-214 was identified by both Cox model and FPCM. Experimental treatment-dependent improvement in the LTB fraction was demonstrated using milestone survival and FPCM. The LTB fraction estimated with FPCM was consistent with the results from the reanalysis of the shorter follow-up period. Although ICIs show substantial shifts toward LTBs in terms of PFS, based on a conventional Kaplan-Meier or Cox model analysis, our approach provides an alternative assessment of benefit-risk ratios for new therapeutics and facilitates communicating risk to patients. Kidney patients treated with ICIs can be counseled that they are potentially cured, but future work will need to definitively validate this conclusion. Although immune checkpoint inhibitor treatments show substantial shifts toward long-term benefits in terms of progression-free survival, a more rigorous attempt to quantify this shift, rather than simply using a Kaplan-Meier estimate or comparing progression-free survival curves using the classic Cox model, is warranted. Our results suggest that advanced renal cell carcinoma patients who had not received a previous treatment are functionally cured by nivolumab and ipilimumab, which is not the case for second-line urothelial carcinoma. [ABSTRACT FROM AUTHOR]

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. 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. 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 [HR strat ] 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], HR strat 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%]). 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. French National Cancer Institute. [ABSTRACT FROM AUTHOR]

The authors comments on a study that investigates the effectiveness of maintenance gemcitabine monotherapy in treating metastatic urothelial cancer, who underwent platinum-based chemotherapy in Paris, France. The authors state that despite the existence of a study on maintenance therapy and its possible implications on the survival of patients, they believed that only clinical, well-designed randomized trial can efficiently evaluate the vital role of MT and gemcitabine in MUC management.

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. [ABSTRACT FROM AUTHOR]