Immediate ADT Improved Survival in Prostate Cancer With Rising PSA

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Immediate ADT improved overall survival compared with delayed ADT in prostate cancer patients with a rising prostate-specific antigen level.

Gillian M. Duchesne, MD, presented results of the trial. Photo © ASCO/Max Gersh 2015.

Immediate assignment to androgen deprivation therapy (ADT) resulted in improved overall survival and time to clinical progression in prostate cancer patients with a rising prostate-specific antigen (PSA) level, according to the results of the phase III TROG 03.06 and VCOG PR 01-03 trial (abstract 5007) presented at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting held May 29 to June 2 in Chicago.

“This trial provides moderate evidence that the use of immediate ADT in men with PSA relapse after primary therapy or with non-curative disease improves overall survival by approximately 10% at 5 years,” said study presenter Gillian M. Duchesne, MD, of Peter MacCallum Cancer Centre in Melbourne.

The trial included 293 patients who had undergone one or more attempts at curative therapy or those with newly diagnosed disease with factors making them ineligible for curative approaches. Men were randomly assigned to immediate ADT (Arm B; n = 142) or delayed ADT (Arm A; n = 151). The primary endpoint of the study was unadjusted overall survival in the intention-to-treat group.

At a median follow-up of 5 years, there were 46 deaths; 16 occurred in the immediate arm and 30 in the delayed arm.

The 5-year overall survival rates were “significantly higher than expected” at 85.6% for immediate ADT compared with 76.4% for delayed ADT. Six-year overall survival was also more favorable for the immediate ADT arm compared with the delayed arm (81.0% vs 65.4%).

Patients in the immediate arm had a 45% reduced risk for death compared with the delayed arm in the unadjusted analysis (hazard ratio [HR] = 0.55; 95% confidence interval [CI], 0.30–1.00; P = .05). However, in the Cox adjusted regression analysis, there was a non-significant difference in survival between the immediate and delayed arms (HR = 0.54; 95% CI, 0.27–1.06; P = .074).

“When we looked at cause-specific survival, we also had some puzzling results,” Duchesne said.

Prostate cancer deaths were reduced in patients assigned to immediate ADT compared with delayed ADT (6 vs 12), but the other causes of death were also reduced in the immediate vs delayed arms (10 vs 18), and neither of the differences were statistically significant.

The researchers also looked at several other disease endpoints and found that immediate assignment to ADT resulted in significantly improved time to first local progression (HR = 0.51; 95% CI, 0.34–0.76; P = .001) and time to first metastatic disease (HR = 0.54; 95% CI, 0.32–0.90; P = .018). However, no significant difference was seen for time to castration resistance (HR = 1.20; 95% CI, 0.94–1.53; P = .14).

“As this is not a curative approach, the benefit must be balanced against the morbidity of the therapy,” Duchesne said.

Among patients assigned to delayed therapy, 47.3% of men reported ADT-related symptoms at least once during the follow-up period compared with 77.9% of men assigned to the immediate ADT arm.

When discussing the results, abstract discussant Celestia S. Higano, MD, FACP, of the University of Washington, said that this has been an “elusive question that has been asked for a long time,” with many trials trying to explore whether immediate ADT is better than delayed ADT. Unfortunately, she added, there are challenges associated with trials exploring this question, including trial accrual often not being reached, patient reluctance to be randomized, and fewer events occurring than predicted, meaning that it might not be possible to answer this question in these kinds of trials.

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