Editor's Commentary - Projecting the clinical benefits of adjuvant radiotherapy versus observation and selective salvage radiotherapy after radical prostatectomy: A decision analysis

BERKELEY, CA (UroToday.com) - Adjuvant radiotherapy (ART) for adverse pathological findings following radical prostatectomy (RP) for prostate cancer (CaP) improves disease control but has associated side effects, and up to 50% of patients with adverse pathology will not have disease recurrence and will thus be overtreated.

In Prostate Cancer and Prostatic Diseases, Dr. S.P. Elliott and collaborators report a decision analysis to better reflect outcomes for patients considering ART versus salvage radiotherapy (SRT).

The investigators used published data from a systematic review of RT after RP. In the reports they found that PSA recurrence rates were significantly higher with observation than ART. They estimated progression probabilities for the base-case analysis from the SWOG trial, as it was the only trial with enough long-term follow-up regarding metastasis and death. They used data from Stephenson’s study to estimate progression probabilities of SRT. They used a Markov model to evaluate clinical outcomes after RP for a theoretical cohort of 65-year old me with locally advanced CaP managed post-surgery with ART or initial observation plus SRT given at an early PSA recurrence. For men on observation they assumed that 75% would receive SRT at PSA recurrence and patients with local recurrence faced a monthly risk of metastasis. Men with a post-RT recurrence were managed with androgen deprivation therapy (ADT). Men were at risk from death from other causes based on the US Life Tables. The prevalence of all possible combinations of adverse side effects (ED, urinary obstruction, urinary incontinence, and bowel dysfunction) was considered for men with and without RT. A sensitivity analysis was also performed.

The created model successfully predicted the 10-year PSA recurrence-free survival in both the observation (28%) and ART (52%) arms of the SWOG trial. It also accurately predicted the metastasis-free survival (71%) and overall survival (74%) in the ART arm. Using corrected 10-year metastasis-free survival values, their model still under-predicted deaths in the observation arm. They thus had to either increase the annual probability of progression from metastasis to death in the observation arm to almost 3-fold that of the adjuvant arm (24% to 67%), or increase the background death rate to equal the rate in the 1996 US Life Table, which is 1.25-fold the rate for the adjuvant arm. The model demonstrated slightly lower 10-year PSA recurrence-free survival rates on observation vs. ART (47% vs. 52%). They found that metastasis-free survival and overall survival were similar between strategies; observation with SRT yielded 28% of men never experiencing a PSA recurrence over 10 years and thus avoiding SRT. Regarding QOL, when disutility of RT was modeled, observation plus SRT was preferred over ART at 10 years. In the sensitivity model, as SRT is delayed until higher PA values, ART becomes preferred over a wider range of effectiveness. Using the base-case values of a probability of PSA recurrence with observation (9.5% per year) and ART (3.9% per year), the two strategies were equivalent when 75% of PSA recurrences received SRT at PSA <0.05ng/ml, however, when SRT was delayed until reaching a higher PSA then ART was preferred.

Elliott SP, Wilt TJ, Kuntz KM 


Prostate Cancer Prostatic Dis. 2011 Sep;14(3):270-7

PubMed Abstract
PMID: 21691281

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