“AUA 2017: Best Prostate Cancer Papers from Past Years”
Prostate Cancer Foundation of Chicago (PCFC) comments on an overview of five impactful papers in prostate cancer research from 2016.
Two important papers in the prostate cancer screening arena included the New England Journal of Medicine letter revaluating PSA testing rates in the PLCO trial, and the GWAS PSA SNPs manuscript. The PLCO 2009 PSA screening trial noted no improvement in survival with PSA screening, however there was a reported 50% contamination rate (men in the control arm receiving PSA screening). This letter looked at rates of testing during the trial, which was administered as a questionnaire to a subgroup of control patients, demonstrating that in fact >80% of controls without baseline screening receiving a PSA test during the trial. This letter was important as it likely contributed to the revised Grade C recommendation among men 55-69 years of age. The GWAS trial identified 40 genome-wide significant SNPs, 19 being novel entities. These 40 SNPs explain 9.5% of PSA variation in non-Hispanic whites, since >50% are PSA associated independent of prostate cancer.
PCFC comments: A letter appearing in the New England Journal of Medicine helped convince US Prevention Services Task Force to reverse its recommendation that men forego prostate cancer screening. PCFC applauds the Task Force decision and early prostate cancer detection.
The PROMIS study was highlighted as an important paper for prostate cancer diagnosis in 2016. This study assessed whether multiparametric MRI (mpMRI) used as a triage test may allow men to avoid an unnecessary TRUS-biopsy and improve diagnostic accuracy. In this multi-center study, 576 men with PSA < 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 to TRUS Bx (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 prostate cancer.
PCFC comments: Stereotactic transperineal mapping biopsy is especially useful for diagnosing and planning treatment for men with low-grade cancer confined to the prostate gland.
The much acclaimed and highly publicized ProtecT trial was highlighted as an important paper in the category of initial treatment for prostate cancer. In this trial 1,643 men with newly diagnosed prostate cancer aggressed to undergo randomization to either active monitoring, surgery or radiotherapy. The primary outcome of PCa-mortality was not reached as only 17 (1%) of patients died of prostate cancer. 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 is that the natural history of prostate cancer is very long and places importance on assessing each patient’s life expectancy. Also, the Australian RCT randomizing 326 men to open vs robotic radical prostatectomy was published in 2016. The major findings of this trial was that there was no difference in urinary or sexual function at three months follow up and no difference in positive margin rate (10% open, 15% robotic). As Dr. Preston mentioned, this shows that surgical RCTs are feasible and should be performed. The ASCENDE-RT was a randomized trial comparing two methods of dose escalation for intermediate and high risk prostate cancer, with all participants receiving 12 months of ADT. After 8 months of ADT, all men received 46 Gy of pelvic XRT followed by a 32 Gy XRT boost, followed by randomization to receive a brachytherapy boost 3 weeks after XRT. Compared to men receiving only XRT, men randomized to brachytherapy boost were twice as likely to be free of biochemical recurrence at 6.5 years of follow-up.
PCFC comments: A combination of radiation therapies may provide the best cure rates for men with more advanced disease. Compared to men receiving only external beam radiation treatment, men randomized to LDR brachytherapy boost (additional radiation supplied via a seed implant) were twice as likely to be free of biochemical recurrence at 6.5 years follow-up.
Several trials in the setting of locally recurrent prostate cancer were highlighted. A double blind, placebo controlled trial among 760 men that 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% vs placebo 71.3% (HR 0.77, p=0.04). A subsequent GETUG multi-center RCT aimed 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 that 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%, HR 0.50, p=<0.001).
PCFC comments: Brachytherapy, or seed implant, is another effective salvage radiation option that can be part of treatment for patients with recurrent prostate cancer.
The final paper, in the metastatic setting, highlighted the frequency of inherited mutations in DNA-repair genes (ie. BRCA2) in patients with metastatic prostate cancer. Among 692 men, 20 DNA repair genes were assessed; 11.8% of men with metastatic disease had inherited DNA-repair gene mutations, significantly higher than men with localized prostate cancer. The implications of these findings are that this will allow us to identify men that may have sustained responses to PARP inhibitors and platinum-based chemotherapy.
PCFC comments: Inherited mutations of the BRCA1 or BRCA2 genes can raise the risk of breast, ovarian and prostate cancer in some families.
Speaker: Mark A. Preston, Harvard Medical School, Boston, MA, USA
Original blog written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre
Twitter: @zklaassen_md at the 2017 AUA Annual Meeting – May 12 – 16, 2017 – Boston, Massachusetts, USA