Dismantling papillary renal cell carcinoma classification: The heterogeneity of genetic profiles suggests several independent diseases.

Papillary renal cell carcinoma (pRCC) is the second most frequent renal cell carcinoma (RCC) after clear cell RCC. In contrast to clear cell RCC, there is no consensual protocol using targeted therapy for metastatic pRCC. Moreover, diagnosis of some pRCC, especially pRCC of type 2 (pRCC2) may be challenging. Our aim was to identify molecular biomarkers that could be helpful for the diagnosis and treatment of pRCC. We studied the clinical, histological, immunohistological, and comprehensive genetic features of a series of 31 pRCC including 15 pRCC1 and 16 pRCC2. We aimed to determine whether pRCC represents a unique entity or several diseases. In addition, we compared the genetic features of pRCC2 to those of eight RCC showing various degrees of tubulo-papillary architecture, including three TFE-translocation RCC and five unclassified RCC. We demonstrate that pRCC is a heterogeneous group of tumors with distinct evolution. While most pRCC2 had genetic profiles similar to pRCC1, some shared genomic features, such as loss of 3p and loss of chromosome 14, with clear cell RCC, TFE-translocation RCC, and unclassified RCC. We identified variants of the MET gene in three pRCC1. A mutation in the BRAF gene was also identified in one pRCC1. In addition, using next-generation sequencing (NGS), we identified several variant genes. Genomic profiling completed by NGS allowed us to classify pRCC2 in several groups and to identify novel mutations. Our findings provide novel information on the pathogenesis of pRCC that allow insights for personalized treatment.

The relevance of testing the efficacy of anti-angiogenesis treatments on cells derived from primary tumors: a new method for the personalized treatment of renal cell carcinoma.

Despite the numerous available drugs, the most appropriate treatments for patients affected by common or rare renal cell carcinomas (RCC), like those associated with the Xp11.2 translocation/transcription factor for immunoglobulin heavy-chain enhancer 3 (TFE3) gene fusion (TFE3 RCC), are not clearly defined. We aimed to make a parallel between the sensitivity to targeted therapies on living patients and on cells derived from the initial tumor. Three patients diagnosed with a metastatic RCC (one clear cell RCC [ccRCC], two TFE3 RCC) were treated with anti-angiogenesis drugs. The concentrations of the different drugs giving 50% inhibition of cell proliferation (IC50) were determined with the Thiazolyl Blue Tetrazolium Bromide (MTT) assay on cells from the primary tumors and a reference sensitive RCC cell line (786-O). We considered the cells to be sensitive if the IC50 was lower or equal to that in 786-O cells, and insensitive if the IC50 was higher to that in 786-O cells (IC 50 of 6 ± 1 µM for sunitinib, 10 ± 1 µM for everolimus and 6 ± 1 µM for sorafenib). Based on this standard, the response in patients and in cells was equivalent. The efficacy of anti-angiogenesis therapies was also tested in cells obtained from five patients with non-metastatic ccRCC, and untreated as recommended by clinical practice in order to determine the best treatment in case of progression toward a metastatic grade. In vitro experiments may represent a method for evaluating the best first-line treatment for personalized management of ccRCC during the period following surgery.

High-dose rate brachytherapy in localized penile cancer: short-term clinical outcome analysis.

PURPOSE: To assess clinical outcomes of high-dose rate interstitial brachytherapy (HIB) in localized penile carcinoma. MATERIAL AND METHODS: From 03/2006 to 08/2013, patients with biopsy-proven T1-T2 (<4 cm) non-metastatic localized penile squamous cell carcinoma underwent HIB. Under general anaesthesia, after Foley catheter placement, needles were placed in the target volume using a dedicated template. Planification was carried out with a post-implant CT-scan to deliver a total dose of 36 Gy in 9 fractions over 5 days (in adjuvant setting) or 39 Gy in 9 fractions over 5 days (as monotherapy). Dose-volume adaptation was manually achieved using graphical optimization. Dosimetric data and clinical outcomes were retrospectively analyzed. Toxicities were graded using the CTC v4.0. RESULTS: With a median follow-up of 27 months [5.1-83], 12 patients including 8 T1a, 3 T1b and 1 T2 N0 underwent HIB (sole therapy: 11 pts; adjuvant: 1 pt). The actuarial 5-year relapse-free, cause-specific and overall survival rates were 83%, 100% and 78% respectively. Comparing pre and post treatment evaluation, no IPSS or IIEF-5 changes were reported. Dermatitis was reported systematically 1 month after HIB including 6 G1, 5 G2 and 1 G3. Only 1 experienced long-term G3 successfully treated with hyperbaric oxygen therapy. One urethral meatus stenosis G3 required meatotomy. CONCLUSION: In selected patients with T1-T2 localized penile cancer, HIB may be considered as an optional conservative therapy. Longer follow-up is needed to confirm these encouraging preliminary results.