Active surveillance for non-muscle invasive bladder cancer: A systematic review and pooled-analysis

ABSTRACT Introduction One of the Non-Muscle Invasive Bladder Cancer (NMIBC) treatment options recently recommended by International Guidelines is represented by Active Surveillance (AS),. Herein we carried out a systematic review and pooled-analysis of currently available evidences in order to provide recommendations for daily urological practice. Material and Methods The PubMed, EMBASE, and Coch rane Library databases were searched with the terms "Non-Muscle Invasive" or "pTa/pT1" and "Bladder Cancer" or "Bladder Tumor". A meta-analysis was conducted to estimate the pooled upstage rate (from pTa to pT1/T2), the pooled upgrade (from G1–2 to G3), the proportion of pts still in AS and the pooled AS failure rate across all studies. A random-effects model was used to derive the pooled effect sizes and the 95% confidence intervals (CIs). Results 7 studies were included, accounting for 558 patients (pts). AS failure rate was 67% (95%CI 44–84%) and 32% of pts were still on AS (14–56%) during a median AS time of 15,6 months. Progression to worst grade or stage was observed in 19% of pts (95%CI 11–30%). Upgrade to G3 and upstage to pT1 were observed in 44% (95%CI 13.6–79.8%) and 8% (95%CI 3.9–15.9%) respectively. Conclusions AS for Low Grade NMIBC can be considered safe and feasible, even if only in clinical trial context. We encourage multicenters to perform randomized clinical trials to obtain data about the quality of life of pts on AS, which are scarce, and to rapidly make AS an integral part of daily urological practice as soon as possible

Patterns of Disease Progression and Outcome of Patients With Testicular Seminoma Who Relapse After Adjuvant or Curative Radiation Therapy.

PURPOSE Radiation therapy is a possible treatment strategy for patients with testicular seminoma after orchiectomy in clinical stage I or II disease. Little is known about the outcome of patients who experience a relapse after radiation therapy. METHODS AND MATERIALS Data from 61 patients who relapsed after adjuvant or curative radiation therapy from 17 centers in 11 countries were collected and retrospectively analyzed. Primary outcomes were disease-free and overall survival. Secondary outcomes were time to relapse, stage at relapse, treatment for relapse, and rate of febrile neutropenia during chemotherapy for relapse. RESULTS With a median follow-up of 9.9 years (95% confidence interval [CI], 7.5-10.9), we found a 5-year disease-free survival of 90% (95% CI, 79-95) and a 5-year overall survival of 98% (95% CI, 89-100). Sixty-six percent of patients had stage III disease at time of relapse and 93% of patients fell into the good prognosis group per the International Germ Cell Cancer Collaborative Group classification. The median time to relapse after radiation therapy was 15.6 months (95% CI, 12-23). Twenty-two (36%) patients relapsed more than 2 years after radiation therapy and 7 (11.5%) patients relapsed more than 5 years after radiation therapy. One-third of relapses was detected owing to patients' symptoms, whereas two-thirds of relapses were detected during routine follow-up. The majority (93%) of cases were treated with cisplatin-based chemotherapy. The rate of febrile neutropenia during chemotherapy was 35%. Five patients experienced a second relapse. At last follow-up, 55 patients (90%) were alive without disease. Only 1 patient died owing to disease progression. CONCLUSIONS Cisplatin-based chemotherapy for patients with seminoma who have relapsed after treatment with radiation therapy alone leads to excellent outcomes. Patients and physicians should be aware of possible late relapses after radiation therapy

Palliative treatment of germ cell cancer.

Most patients with metastatic germ-cell cancer (GCC) can be cured by cisplatin-based combination chemotherapy. Yet, about 10-15% of metastatic GCC patients will eventually die of their disease. This narrative review focuses on treatment options when cure is no longer realistic

Clinical experience with temsirolimus in the treatment of advanced renal cell carcinoma

Temsirolimus is an inhibitor of the mammalian target of rapamycin (mTOR) kinase, a protein that has been shown to be particularly active in metastatic renal cell carcinoma (mRCC) with poor prognosis. Therefore, temsirolimus should be considered as the first-line treatment indicated in mRCC patients classified as poor risk. The benefits of temsirolimus are not limited to an increased survival but are also related to a better quality of life, which is certainly one of the most important aspects in the clinical management of these frail patients. Temsirolimus is a well-tolerated treatment, and the most frequent adverse events are manageable with supportive care. To this end, the identification of predictive factors of response to temsirolimus could help us to better select patients and obtain a more tailored clinical management of mRCC

Cabozantinib as First-line Treatment in Patients With Metastatic Collecting Duct Renal Cell Carcinoma: Results of the BONSAI Trial for the Italian Network for Research in Urologic-Oncology (Meet-URO 2 Study)

Importance: Metastatic collecting duct carcinoma (mCDC) is a rare type of non-clear cell renal cell carcinoma (ncRCC) with poor prognosis and no standard treatments. Despite retrospective series that have documented the benefit of cabozantinib in ncRCC, no prospective trials have evaluated this treatment in mCDC. Objective: To determine whether cabozantinib is an active treatment in patients with mCDC. Design, setting, and participants: The caBozantinib in cOllectiNg ductS Renal Cell cArcInoma (BONSAI) trial was an open-label, single-arm, phase 2 clinical trial carried out between January 2018 and November 2020 at a single academic center with data cut off in September 2021 on behalf of the the Italian Network for Research in Urologic-Oncology (Meet-URO 2). Eligible patients had histologic diagnosis of centrally confirmed mCDC with measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST; version 1.1). In total, 25 patients were screened. Interventions: Patients received cabozantinib, 60 mg orally once daily, until disease progression, unacceptable toxic effects, or withdrawal of consent. Main outcomes and measures: The primary end point was objective response rate (ORR) per RECIST, version 1.1. Results: At data cut off, of 25 patients enrolled, 23 started treatment because 2 were excluded after failing the screening process at pathologic review. The median follow-up cannot be estimated using the reverse Kaplan-Meier estimator. The median time to censoring was 11 months (95% CI, 0-22 months). Median (range) age was 66 (53-74) years. As best overall response, 3 patients presented stable disease, 1 patient achieved a complete response, and 7 a partial response. The ORR was 35% (95% CI, 16%-57%). The median progression-free survival was 4 months (95% CI, 3-13 months). The median OS was 7 months (95% CI, 3-31 months). All patients reported at least 1 grade (G) 1 to 2 adverse event (AE). The most common G1 to G2 AEs were fatigue (14 [60%]), anorexia (9 [39%]), hand-foot syndrome (7 [30%]), hypothyroidism (7 [30%]), mucositis (7 [30%]), diarrhea (5 [22%]), and hypertension (3 [13%]). Six G3 AEs were reported: 2 arterial hyperthension, 1 pulmonary thromboembolism, 1 bleeding, and 2 fatigue. There were no permanent discontinuations from the study owing to AEs. Four patients (17%) required dose reduction to 40 mg, and 4 (17%) required a transitory interruption to manage toxic effects. Conclusions and relevance: The study met the ORR primary end point, showing encouraging efficacy of cabozantinib in untreated patients with mCDC. Further investigations to advance the molecular understanding of this tumor are ongoing. Trial registration: ClinicalTrials.gov Identifier: NCT03354884