DNA damage repair gene germline profiling for metastatic prostate cancer patients of different ancestries.

BACKGROUND: Germline and somatic mutations in DNA damage repair genes (DDRg) are now recognized as new biomarkers for the management of metastatic prostate cancers (mPC). We evaluate the frequency of germline DDRg mutations among French mPC patients of European and African ancestries. METHODS: Targeted next-generation sequencing of 21 DDRg was performed on germline DNA from 557 mPC patients, including 15.1% of cases with an African origin. RESULTS: Forty-seven germline mutations in 11 DDR genes were identified in 46 patients of the total cohort (8.3%). BRCA2 (4.1%) and ATM (2.0%) were the most frequently mutated genes. There was no difference in DDRg mutation frequency between mPC patients of European ancestry and those of African origin. Germline mutations of BRCA2 were associated with a positive family history of breast cancer (p = 0.02). The mean age at metastatic stage (59.7 vs. 67.0; p = 0.0003) and the mean age at death (65.2 vs. 73.9; p = 0.0003) were significantly earlier for carriers of BRCA2 mutation than for non-carriers. Moreover, the Cox model showed that BRCA2 positive status was statistically associated with poorer survival (hazard ratio: 0.29; 95% confidence interval 0.18-0.48; p < 0.0001). CONCLUSION: We showed that, in France, BRCA2 and ATM are the main predisposing DDR genes in mPC patients, with a particular aggressiveness for BRCA2 leading to early metastatic stage and death.

PDE-5i Management of Erectile Dysfunction After Rectal Surgery: A Systematic Review Focusing on Treatment Efficacy.

Erectile dysfunction (ED) is one of the main functional complications of surgical resections of the rectum due to rectal cancers or inflammatory bowel disease (IBD). The present systematic review aimed at revising ED management strategies applied after rectal resections and their efficacy in terms of improvement of the International Index of Erectile Function (IIEF) score. A literature search was conducted on Medline, EMBASE, Scopus, and Cochrane databases by two independent reviewers following the PRISMA guidelines. Randomized and nonrandomized controlled trials (RCTs, NRCTs), case-control studies, and case series evaluating medical or surgical therapies for ED diagnosed after rectal surgery for both benign and malignant pathologies were eligible for inclusion.Out of 1028 articles initially identified, only five met the inclusion criteria: two RCTs comparing oral phosphodiesterase type-5 inhibitor (PDE-5i) versus placebo; one NRCT comparing PDE-5i versus PDE-5i + vacuum erection devices (VEDs) versus control; and two before-after studies on PDE-5i. A total of 253 (82.7%) rectal cancer patients and 53 (17.3%) IBD patients were included. Based on two RCTs, PDE-5i significantly improved IIEF compared to placebo at 3 months (SMD = 1.07; 95% CI [0.65, 1.48]; p < .00001; I2 = 39%). Improved IIEF was also reported with PDE-5i + VED at 12 months. There is a paucity of articles in the literature that specifically assess efficacy of ED treatments after rectal surgery. Many alternative treatment strategies to PDE-5is remain to be investigated. Future studies should implement standardized preoperative, postoperative, and follow-up sexual function assessment in patients undergoing rectal resections.