Guideline-Concordant Multimodality Care Tied to Fewer Deaths in High-Risk Prostate Cancer

By Marilynn Larkin

July 09, 2021

NEW YORK (Reuters Health) - In high-risk prostate cancer patients with at least one additional adverse feature, guideline-concordant multimodal care was associated with greater prostate cancer-specific survival (PCSS) in a large retrospective study.

Guideline-concordant multimodal treatment was defined as radical prostatectomy (RP) with appropriate use of multimodal therapy (optimal RP); external beam radiotherapy (EBRT) with at least two years of androgen deprivation therapy (ADT; optimal EBRT); or EBRT with brachytherapy boost (BT) with at least one year ADT (optimal EBRT with BT).

"For patients with high-risk prostate cancer and at least one additional aggressive feature, survival outcomes were best optimized, and equal, when men received either radiation with standard-of-care hormonal therapy, or surgery with postoperative radiation as intended," Dr. Amar Kishan of the University of California, Los Angeles told Reuters Health by email.

"This is important in resolving the controversy of whether one approach is necessarily superior to the other," he said. "For men receiving 'suboptimal' or 'non-standard; therapy, outcomes were indeed worse, and differences between treatments could more easily be detected."

"These findings did not surprise me, though they may be controversial in the sense that many prior studies - which had significant limitations in information about treatments received -- did find survival differences between management strategies," he said.

"Even with optimal postoperative treatment, the rates of distant metastasis were higher in the upfront surgery group," he added. "This might reflect the fact that hormonal therapy is a standard part of optimal radiation treatment, but is not yet part of the standard surgical treatment strategy. Ongoing trials are evaluating whether adding hormonal therapy to surgical management might improve outcomes."

As reported in JAMA Network Open, data from 6,004 men (median age, 66.4) with high-risk prostate cancer were analyzed: 3,175 (52.9%) underwent RP; 1,830 (30.5%) underwent EBRT alone; and 999 (16.6%) underwent EBRT with BT.

The primary outcome was prostate cancer-specific mortality; the secondary outcome, distant metastasis.

Compared with RP, treatment with EBRT with BT (subdistribution hazard ratio, 0.78) or EBRT alone (sHR, 0.70) was associated with significantly improved prostate cancer-specific mortality. No difference was seen between EBRT with BT and EBRT alone (sHR, 0.89).

No significant differences in prostate cancer-specific mortality were seen across treatment groups among 2,940 patients who received guideline-concordant multimodality treatment (e.g., optimal EBRT alone vs. optimal RP: sHR, 0.76).

However, treatment with EBRT alone or EBRT with BT was consistently associated with lower rates of distant metastasis compared with treatment with RP (e.g., EBRT vs. RP: sHR, 0.50).

Dr. Kishan said, "The major area of future research is better understanding the heterogeneous course that high-risk prostate cancer can take. Some men had great outcomes even with suboptimal treatment, while others had rapidly progressive cancer. I, and others, are studying and evaluating biomarkers that might help us understand the drivers of these outcomes."

Dr. Kevin Ginsburg, a Urologic Oncology Fellow at Fox Chase Cancer Center in Philadelphia, commented in an email to Reuters Health, "Aspects of the study design are worth noting. There was minimal overlap in the institutions that contributed patients treated both surgically and with EBRT +/- BT, which raises the concern of selection bias in generating the study cohort."

"There are significant geographic differences in patients that received RP versus EBRT +/- BT. Most (55%) of the patients that were treated with RP were from Europe while the majority of the EBRT and EBRT + BT patients were from the U.S. (78% and 68%, respectively)," he noted. "Social factors, regional variations in practice patterns, and fundamental differences in the European and U.S. healthcare systems may contribute to the subtle differences in PCSS and MFS seen in this study."

"Given the general favorable oncological outcomes with all three treatments - RP, EBRT, and EBRT + BT - important considerations should be given to the quality-of-life implications of each treatment (during) shared decision making," he said.

"Potentially," he added, "the development of genetic biomarkers will identify tumors which are radiosensitive and patients which are less susceptible to the bladder and bowel toxicity of radiotherapy."

SOURCE: JAMA Network Open, online July 1, 2021.