Injectable luteinizing hormone-releasing hormone agonists (e.g., leuprolide) are the standard agents for achieving androgen deprivation for prostate cancer despite the initial testosterone surge and delay in therapeutic effect. The efficacy and safety of relugolix, an oral gonadotropin-releasing hormone antagonist, as compared with those of leuprolide are not known. METHODS In this phase 3 trial, we randomly assigned patients with advanced prostate cancer, in a 2:1 ratio, to receive relugolix (120 mg orally once daily) or leuprolide (injections every 3 months) for 48 weeks. The primary end point was sustained testosterone suppression to castrate levels (<50 ng per deciliter) through 48 weeks. Secondary end points included noninferiority with respect to the primary end point, castrate levels of testosterone on day 4, and profound castrate levels (<20 ng per deciliter) on day 15. Testosterone recovery was evaluated in a subgroup of patients. RESULTS A total of 622 patients received relugolix and 308 received leuprolide. Of men who received relugolix, 96.7% (95% confidence interval [CI], 94.9 to 97.9) maintained castration through 48 weeks, as compared with 88.8% (95% CI, 84.6 to 91.8) of men receiving leuprolide. The difference of 7.9 percentage points (95% CI, 4.1 to 11.8) showed noninferiority and superiority of relugolix (P<0.001 for superiority). All other key secondary end points showed superiority of relugolix over leuprolide (P<0.001). The percentage of patients with castrate levels of testosterone on day 4 was 56.0% with relugolix and 0% with leuprolide. In the subgroup of 184 patients followed for testosterone recovery, the mean testosterone levels 90 days after treatment discontinuation were 288.4 ng per deciliter in the relugolix group and 58.6 ng per deciliter in the leuprolide group. Among all the patients, the incidence of major adverse cardiovascular events was 2.9% in the relugolix group and 6.2% in the leuprolide group (hazard ratio, 0.46; 95% CI, 0.24 to 0.88). CONCLUSIONS In this trial involving men with advanced prostate cancer, relugolix achieved rapid, sustained suppression of testosterone levels that was superior to that with leuprolide, with a 54% lower risk of major adverse cardiovascular events. (Funded by Myovant Sciences; HERO ClinicalTrials.gov number, NCT03085095.

Fat grafting for correction of PRS-associated soft-tissue defects is receiving heightened acceptance for its ability to restore natural facial contours. While additional fat-grafting procedures may be required with increased disease severity, autologous fat grafting may be a beneficial option as a sole modality to correct PRS-associated soft-tissue atrophy.

Background The transverse upper gracilis (TUG) flap has gained increasing acceptance as a reliable option for breast reconstruction, specifically in patients without adequate abdominal tissue. Three major flap designs of the upper gracilis flap have been proposed to balance volume needs with flap vascularity. A systematic review was performed to identify outcomes of the major gracilis flaps: TUG, vertical-transverse upper gracilis (V-TUG), and longitudinal gracilis myocutaneous (LGM) flaps. This study is the first and only systematic review to date reviewing the variations of the upper gracilis flap in microsurgical breast reconstruction. Methods A systematic review of the literature was conducted using PubMed database from 1966 through 2015. Inclusion and exclusion criteria were applied. Outcomes assessed included total flap volumes, additional breast procedures to achieve intended breast volume, and complication rates. Results A total of 485 gracilis-type flaps were performed in 335 patients. V-TUG flaps provided the largest mean flap weights and did not require additional lipofilling or implant placement, whereas the majority of TUG flaps (50.6%) required additional fat grafting or implant placements. All flap types demonstrated a low incidence of donor-site morbidity. Overall flap loss rate was low; TUG flaps reported 2.3% total and 2.0% partial flap losses, while V-TUG and LGM flaps reported no flap losses. Conclusion This review found V-TUG yielded highest mean flap weights and did not require additional breast augmentation procedures as compared with the TUG. Also, the V-TUG was a safer donor-site option with fewer flap and donor-site morbidities.

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