[Systemic treatment of locally advanced or metastatic penile cancer]. / Traitement systémique du cancer du pénis localement avancé ou métastatique.

Penile cancers are rare, the vast majority is represented by squamous cell carcinoma, with HPV virus being found in 30 to 40% of cases. At a locally advanced or metastatic stage, first-line treatment relies on platinum and taxane based polychemotherapy. The prognosis for advanced or metastatic penile cancer remains poor, with overall survival ranging from 13.9 to 17.1 months. After the first line, guidelines recommend various chemotherapy treatments or targeted anti-EGFR therapies whose results as well as the level of evidence are limited. A better understanding of the oncogenic pathways involved in penile cancer and a frequent expression of PD-L1 are the rationale for the elaboration of new strategies. This review article presents the data, guidelines and ongoing studies in locally advanced or metastatic penile cancer.

[Radiotherapy of oligometastases: Sequences and interactions with systemic therapies, example of kidney cancer]. / Radiothérapie des oligométastases : interactions/séquences avec thérapies systémiques, exemple du cancer du rein.

This article is a review of the literature that aims to clarify the place of systemic and locoregional treatments, with a focus on radiotherapy and surgery in the management of patients with oligometastatic kidney cancer. We have selected articles of interest published in Medline indexed journals. We have also analysed the related guidelines: National Comprehensive Cancer Network (NCCN) 2019, European Association of Urology (EAU) 2019, European Society of Medical Oncology (ESMO) 2019, Association française d'urologie (Afu) 2018 as well as some abstracts of international congresses. The main treatments evaluated were surgery and radiotherapy. We defined the different scenarios conventionally encountered in clinical practice. The evolution of systemic therapies (increased overall survival and response rate) is likely to increase the number of patients potentially accessible to locoregional treatments. The complete analysis of the literature underlines the place of locoregional treatments whatever the scenarios mentioned. Data on stereotactic radiotherapy found a local control rate consistently above 70% in all studies with a maintained response and positive impact on overall survival and progression-free survival. The improvement of overall survival by sequential use of the various therapeutic classes confirms the need for optimization of locoregional treatments in the model of oligometastatic kidney cancer. The dogma of radioresistance must definitely be set aside with current irradiation techniques.

Impact of everolimus blood concentration on its anti-cancer activity in patients with metastatic renal cell carcinoma.

PURPOSE: Everolimus has demonstrated its efficacy in metastatic renal cell carcinoma (mRCC). Preliminary studies have shown high variability of everolimus blood concentrations (EBC). In other settings, its activity was correlated with EBC. We therefore decided to monitor EBC in patients treated with mRCC to assess its influence on oncologic outcomes. PATIENTS AND METHODS: Our study analyzed first 3 months' trough EBC levels in 42 patients treated in 4 French oncologic centers between March 2010 and August 2013. Patients presented a histologically confirmed diagnosis of mRCC and have failed prior anti-angiogenic (AA) therapies. RESULTS: Median follow-up was 25.9 months. A total of 113 EBC were analyzed. The median trough concentration was 14.1 µg/L (range 2.6-91.5). Fourteen patients (67 %) versus 8 (38 %) patients with median EBC above or below 14.1 µg/L were free from progression at 6 months (p = 0.06). Median progression-free survival was 13.3 versus 3.9 months (HR 0.66 95 % CI 0.33-1.31; p = 0.23), and the median overall survival was 26.2 versus 9.9 months (HR 0.62 95 % CI 0.28-1.37; p = 0.24), for patients above or below the median value of trough concentrations, respectively. CONCLUSION: Impact of drug exposure for AA tyrosine kinase inhibitors activity has been demonstrated in mRCC setting. Interpatients EBC variability was confirmed in the present study, and the results suggest a relationship between initial EBC within the first 3 months and the drug activity. It underlines the need to prospectively include EBC monitoring in future clinical trials to determine the need of its implementation in routine use.