Two important papers in the PC screening arena included the New England Journal of Medicine letter re-evaluating prostate-specific-antigen (PSA) testing rates in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial or PLCO trial, and the Genome-wide Association Study PSA single nucleotide polymorphisms (SNPs) manuscript. The PLCO 2009 PSA screening trial noted no improvement in survival with PSA screening, but there was a reported 50% contamination rate (men in the control arm receiving PSA screening). This letter delved into rates of testing during the trial, which was administered as a questionnaire to a subgroup of control patients, demonstrating that, in fact, more than 80% of controls without baseline screening received a PSA test during the trial. The letter was important since it likely contributed to the revised Grade C recommendation among men 55 to 69 years of age. The Genome-wide Association Study trial identified 40 genome-wide significant SNPs, 19 of them being novel entities. These 40 SNPs explained 9.5% of PSA variations in non-Hispanic whites, since more than 50% are PSA-associated, independent of PC.
The PROMIS Study was highlighted as an important paper for PC diagnosis in 2016, assessing whether multiparametric magnetic resonance imaging (mpMRI) used as a triage test may allow men to avoid an unnecessary transrectal ultrasound-guided prostate biopsy and improve diagnostic accuracy. In this multicenter study, 576 men with a PSA of less than 15 ng/mL underwent an mpMRI followed by a transperineal mapping biopsy. The study found that for significant cancer, mpMRI was more sensitive (93%) compared with transrectal ultrasound-guided prostate biopsy (48%), but less specific (41% vs. 96%). Using mpMRI to triage men may allow 27% of patients to avoid a primary biopsy and diagnose 5% fewer clinically insignificant PC.
The much acclaimed and highly publicized ProtecT Trial was highlighted as an important paper in the category of initial treatment for PC. In this trial, 1643 men with newly diagnosed PC agreed to undergo randomization to either active monitoring, surgery, or radiotherapy. The primary outcome of PC mortality was not reached as only 17 (1%) patients died of PC. The monitoring group was more likely to have progression or develop metastatic disease, and there was no significant difference between radiation and surgical treatment. The main emphasis of this trial was that the natural history of PC is very long and places importance on assessing each patient’s life expectancy. Also, the Australian randomized, controlled trial subjecting 326 men to open versus robotic radical prostatectomy was published in 2016. The trial’s major findings were that there was no difference in urinary or sexual function at three months’ follow-up and no difference in positive marign rate (10% open, 15% robotic). As Dr. Preston mentioned, this showed that surgical randomized, controlled trials are feasible and should be performed. The ASCENDE-RT was a randomized trial comparing two methods of dose escalation for intermediate- and high-risk PCa, with all participants receiving 12 months of androgen deprivation therapy (ADT). After 8 months of ADT, all men received 46-Gy of pelvic external-beam radiation therapy (XRT) followed by a 32-Gy XRT boost, and then randomization to receive a brachytherapy boost 3 weeks after XRT. Compared with men receiving only XRT, those randomized to brachytherapy boost were twice as likely to be free of biochemical recurrence at 6.5 years’ follow-up.
Several trials in the setting of locally recurrent PCa were highlighted. A double-blind, placebo-controlled trial involving 760 men who underwent prostatectomy with a pT2 or pT3, N0 with a PSA of 0.2 to 4.0 ng/mL set to undergo radiation therapy were randomized to either 24 months of bicalutamide or placebo. The trial found that the addition of bicalutamide to salvage XRT resulted in significantly higher overall survival rates: 12 year—bicalutamide 76.3% versus placebo 71.3% (hazard ratio 0.77, P = .04). A subsequent GETUG multicenter RCT was designed to establish the effect of adding short-term ADT at the time of salvage XRT on biochemical outcome and overall survival among men with rising PSA. There were 743 men who were randomized to salvage XRT or salvage XRT plus short-term goserelin. The results showed that XRT + goserelin resulted in improved 5-year PFS (80% vs. 62%, hazard ratio 0.50, P = <.001).
The final paper, in the metastatic setting, highlighted the frequency of inherited mutations in DNA-repair genes (ie, BRCA2) in patients with metastatic PCa. Among 692 men, 20 DNA repair genes were assessed; 11.8% of individuals with metastatic disease had inherited DNA-repair gene mutations, which were significantly higher than in those with localized PCa. The implications of these findings are that they will allow us to identify men who may have sustained responses to poly (ADP-ribose) polymerase or PARP inhibitors and platinum-based chemotherapy.
Presented By: Mark A. Preston, MD, Harvard Medical School, Boston, MA, USA
Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, Toronto, Ontario, Canada
at the 2017 AUA Annual Meeting - May 12 - 16, 2017 – Boston, Massachusetts, USA