LINE-1 as a therapeutic target for castration-resistant prostate cancer

International audienceProstate cancer is the third leading cause of death by cancer in men. Surgery or hormone deprivation usually contains the progression of the local forms of the disease. In metastatic situations, chemotherapy or second generation hormone therapies are used with an overall survival that never exceeds 36 months when tumors become resistant to castration. In the search for new alternatives, clinical trials with various classes of anticancer drugs have been performed, including chemotherapies, targeted therapies with kinase inhibitors, radium-223, or immunotherapies with somehow limited efficacy. Targeting LINE-1 with reverse transcriptase inhibitors was also proposed as an attractive strategy as retrotransposons may play a role in the initiation and the progression of prostate cancers. After reviewing the biological rational to use RT inhibitors in the treatment of prostate cancers, we will discuss the results of the phase II trial evaluating the efficacy of Efavirenz in the treatment of castration-resistant prostate cancers with a particular emphasis on pharmacokinetics data that were obtained. We will also discuss the positioning of other RT inhibitors in the current therapeutic armamentarium

[Non-surgical treatment modalities available for the treatment of upper tract urothelial carcinomas: state-of-the-art for the yearly scientific report of the French National Association of Urology]

INTRODUCTION: Our purpose was to provide a state-of-the-art regarding the different non-surgical treatment modalities available for urologists in the modern management of upper urinary tract carcinoma (UTUC). MATERIALS AND METHODS: A systematic review of the literature was carried out on Medline and Embase databases: urinary tract; urothelial carcinoma; ureteral cancer; renal pelvis cancer; chemotherapy; radiotherapy; instillation. RESULTS: The medical treatment of UTUC is based on the extrapolation of data coming from bladder cancer studies. It is based on instillation of topical agents in the upper tract, chemotherapy or radiotherapy. However, the fact that UTUCs are scarce and the lack of randomized prospective trials do not provide definitive conclusions on the impact of these treatments. CONCLUSION: The optimal medical management of UTUC is mostly based on expert's opinion so far in combination with the surgical treatment. The international collaborations for UTUC that have been developed in recent years should provide concrete answers in the near future

Formal consensus method to evaluate the conformity of prescription of a recently approved chemotherapy treatment in an observatory study.

Cabazitaxel is a second line chemotherapy drug recently approved for the treatment of metastatic castration-resistant prostate cancer. A first panel of French experts and a second independent panel of European experts were convened to assess the conformity of prescription of cabazitaxel with a Delphi consensus method. A two-round modified Delphi consensus process was conducted. This methodology is based on experts' opinion obtained in a systematic manner. The process was divided into five steps: (i) elaboration of the questionnaire, (ii) rating, (iii) analysis, (iv) discussion of the points with absence of consensus following rating of the questionnaire, and (v) final reporting. Consensus was defined according to RAND method and all analyses were conducted according to the same methodology. At the end of the two rounds of rating and a synthesis meeting, of the 26 items included in the Summary of Product Characteristics (SPC), 11 items were judged appropriate with strong consensus by the two independent panels of experts. These items can therefore be considered of prime importance to evaluate conformity of cabazitaxel prescription in the context of observatory studies as well as in further clinical trials using this new taxane. Our findings further provide important evidence about the value of the Delphi consensus and highlight a requirement for "conformity" standards to assist practitioners in a safe chemotherapy drug prescription

Staged Radiofrequency Ablation and Surgical Resection for Multiple Lung Metastases of Germ Cell Tumors

Purpose: To evaluate the morbidity and efficacy of percutaneous radiofrequency ablation (RFA) performed before surgical resection for multiple residual lung metastases of germ cell tumors with negative tumor markers. Materials and Methods: This Review Board-approved retrospective study was carried out on five consecutive patients (mean age: 31 years, range: 22–41) treated successively with percutaneous RFA and surgery for multiple lung metastases of germ cell tumors. Mean number of lung metastases before treatment was 9.4. Staged procedures were performed on an average of 7.2 months (range: 1–16) after the primitive tumor resection. Results: The median clinical and imaging follow-up was 26 months (range: 24–36). Percutaneous RFA was technically feasible in one session under general anesthesia and CT guidance in all cases. On average, 2.8 tumors were ablated per patient (range: 1–6), and three of five procedures were bilateral. Three patients developed pneumothorax requiring drainage, but no severe complications were reported. Mean time between RFA and surgical resection of residual tumors was 2.5 months (range: 1–5). No local recurrences were noted, but one patient died due to metastatic evolution. Conclusion: Staged percutaneous RFA and surgical resection could be efficient with low morbidity for the management of multiple lung metastases of germ cell tumors

Clinical Relevance of Routine Monitoring of Patient-reported Outcomes Versus Clinician-reported Outcomes in Oncology

International audienceThe National Cancer Institute Common Terminology Criteria for Adverse Events classification is the standard classification used by the physicians in oncology for reporting adverse events. This classification has evolved over the last years according to the emergence of new therapies. Reporting symptoms, quality of life (QoL) and toxicities via patient-reported outcomes (PROs) in clinical practice is not yet a standard of care, nevertheless many studies have been conducted recently to assess feasibility and impact of routine monitoring of PROs, which should enable for better management of toxicities and earlier detection of disease progression in a more patient-centered health care delivery system. The aim of this article was to discuss the advantages and limitations of both approaches, clinicians-reported outcomes and PROs. Growing evidence supports that the routine collection of PROs leads to improvement of QoL and overall survival of cancer patients

Impacts de la mesure des patient-reported-outcomes en routine clinique en oncologie

International audienc

Innovation in Radionuclide Therapy for the Treatment of Prostate Cancers: Radiochemical Perspective and Recent Therapeutic Practices

Prostate cancer represents the second cause of death by cancer in males in western countries. While early-stage diseases are accessible to surgery and/or external radiotherapy, advanced metastatic prostate cancers are primarily treated with androgen deprivation therapy, to which new generation androgen receptor antagonists or taxane-based chemotherapies are added in the case of tumor relapse. Nevertheless, patients become invariably resistant to castration with a median survival that rarely exceeds 3 years. This fostered the search for alternative strategies, independent of the androgen receptor signaling pathway. In this line, radionuclide therapies may represent an interesting option as they could target either the microenvironment of sclerotic bone metastases with the use of radiopharmaceuticals containing samarium-153, strontium-89 or radium-223 or tumor cells expressing the prostate-specific membrane antigen (PSMA), a protein found at the surface of prostate cancer cells. This review gives highlights the chemical properties of radioligands targeting prostate cancer cells and recapitulates the clinical trials evaluating the efficacy of radionuclide therapies, alone or in combination with other approved treatments, in patients with castration-resistant prostate tumors. It discusses some of the encouraging results obtained, especially the benefit on overall survival that was reported with [177Lu]-PSMA-617. It also addresses the specific requirements for the use of this particular class of drugs, both in terms of medical staff coordination and adapted infrastructures for efficient radioprotection

Gene Expression Signature Predicting High-Grade Prostate Cancer Responses to Oxaliplatin

International audienc

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Impact on quality of life 3 years after diagnosis of prostate cancer patients below 75 at diagnosis: an observational case-control study

International audienceBackground: Prostate cancer patients are known to suffer from poor sexual and urinary long-term side-effects following treatment, potentially impacting quality of life. The purpose of our study was to compare health-related quality of life at 3 years between prostate cancer patients and healthy controls according to key lifestyle characteristics. Secondary objectives were to compare urological dysfunction, sexual function, anxiety and depression. Methods: Multicentric, case-control, observational prospective, open, follow-up study including 819 prostate cancer patients < 75 years old from the EPICAP cohort, newly diagnosed from 1 December 2011 to 31 March 2014 and 879 healthy controls. Participants were excluded if they experienced a relapse. Controls from the same geographical region were age-matched and were excluded if they were diagnosed with prostate cancer. Patients received one of the following treatments: active surveillance (AS), radical prostatectomy (RP), external beam radiotherapy (EBRT), High-intensity Focused Ultrasound (HIFU), chemotherapy (CT), or androgen deprivation therapy (ADT) as appropriate. The primary outcome was the quality of life as evaluated by the QLQ-C30 questionnaire. Scores were analyzed by multivariate analysis to adjust for predefined socio-demographic confounding effects.Results: In total, 564 participants were included (mean age 67.9 years): 376 patients and 188 controls. Treatment breakdown was: 258 underwent RP, 90 received EBRT, 52 brachytherapy or HIFU, 15 CT, 26 ADT and 61 AS. There was no difference in median global quality of life between patients and controls (94.87 vs 94.15, p = 0.71). Multivariate analysis showed poorer social functioning in patients (24.3% vs. 16.3%, p = 0.0209), more dyspnea (22% vs. 12.4%, p = 0.0078), and yet less current pain (23% vs 33%, p = 0.0151).Conclusions: Global health status score at 3 years after diagnosis was similar between patients and controls, though patients showed a significantly worse social functioning. Prostate cancer diagnosis per se does not seem to impact the quality of life of patients < 75 years at diagnosis. However, the therapeutic option that will be chosen following diagnosis should be carefully discussed with the medical staff in terms of benefit-risk ratios as it could have a long-term impact on urinary or erectile dysfunctio