According to recent estimates, fewer than 10% of men diagnosed with prostate cancer present with Gleason score as high as 9 or 10. “Although these patients represent a small subset of men with the disease, it is important to treat them appropriately because they account for most prostate cancer–specific deaths,” explains Anthony V. D’Amico, MD, PhD. “Unfortunately, research suggests many patients with these high Gleason scores may not receive guideline-recommended follow-up treatments after their initial treatment.”

Several studies have compared radical prostatectomy (RP) with external beam radiotherapy (EBRT) in men with favorable-risk prostate cancer, but few have compared mortality with these procedures in men with high-risk prostate cancer. In a previous study, it was noted that that treatment of patients with Gleason score 9-10 prostate cancer using a combination of EBRT, brachytherapy, and androgen deprivation therapy (ADT) (termed MaxRT) for an average of 12 months was associated with lower risk of prostate cancer–specific mortality when compared with RP. However, studies comparing MaxRT with RP and adjuvant EBRT, ADT, or both (termed MaxRP) are lacking.

“Comparisons of these treatment approaches are needed because recent clinical trials have shown that some strategies can result in a significantly prolonged disease-free survival and overall survival when appropriate use of adjuvant and/or salvage treatment after surgery is employed,” notes Dr. D’Amico.”


New Data

To address this research gap, Dr. D’Amico and colleagues evaluated if treatment of men with Gleason score 9-10 prostate cancer using RP and appropriate use of adjuvant EBRT, ADT, or MaxRP versus MaxRT was associated with a difference in mortality risk. The study, published in JAMA Oncology, consisted of 639 men with clinical T1-4, N0M0 biopsy Gleason score 9-10 prostate cancer, 80 of whom were treated with MaxRT and 559 with MaxRP. The authors assessed for treatment propensity score-adjusted risk of prostate cancer–specific and all-cause mortality as well as an evaluation of the likelihood of equivalence of these risks between treatment by using a plausibility index.

After a median follow-up of 5.51 years for patients receiving MaxRT and 4.78 years for those receiving MaxRP, the study team found that a total of 161 patients had died, 65.8% (or 106) of whom fell into the prostate cancer–specific mortality category. “Importantly, the plausibility indexes for equivalence were 76.75% for the endpoint of the risk of prostate cancer–specific mortality and 77.97% for the endpoint of the risk of all-cause mortality,” Dr. D’Amico says. For all other treatment comparisons, these respective values ranged from 4.75% to 58.24% and from 4.62% to 62.32% (Table).


Analyzing Implications

The research team noted it is plausible that treatment with MaxRP or MaxRT for men with high-risk prostate cancer provides equivalent survival outcomes. However, Dr. D’Amico cautions that these data are not a substitute for a randomized clinical trial. To his knowledge, there are no ongoing or planned clinical trials that stratify by Gleason score 9-10 or randomized equivalence trials comparing prostate cancer–specific and all-cause mortality after MaxRP vs MaxRT for these types of patients.

Regardless of whether men with Gleason score 9-10 prostate cancer receive surgery or radiotherapy, it is critical to monitor PSA levels, follow them closely for any indications of residual disease, and ensure receipt of subsequent guideline-recommended treatments. “The data presented in our study are the only data that exist which take into account guideline-based use of both adjuvant RT and ADT after RP,” says Dr. D’Amico. “It is also the only data showing with about 80% certainty that patients with Gleason score 9-10 prostate cancer have a choice when it comes to their treatment options being Max RT or Max RP.”