Adjuvant radiation therapy may delay post-radical prostatectomy cancer progression

January 1, 2010

Post-prostatectomy patients with undetectable PSA levels but who have high-risk features in the prostatectomy specimen can delay biochemical progression by undergoing immediate radiotherapy (RT) rather than waiting for salvage radiotherapy once it occurs.

Key Points

Berlin-Post-prostatectomy patients with undetectable PSA levels but who have high-risk features in the prostatectomy specimen can delay biochemical progression by undergoing immediate radiotherapy (RT) rather than waiting for salvage radiotherapy once it occurs, according to research by Belgian investigators.

Prospective, randomized, controlled trials have shown that adjuvant RT after radical prostatectomy improves all clinical endpoints compared to observation in patients with extracapsular extension, seminal vesicle invasion, or positive surgical margins (JAMA 2006; 296:2329-35; J Urol 2009; 181:956-62; Lancet 2005; 366:572-8; J Clin Oncol 2009; 27:2924-30).

It is unclear, however, whether salvage RT upon PSA relapse might offer the same benefit as adjuvant RT in patients with negative surgical margins, said Tom Budiharto, MD, a clinical research fellow in the department of radiotherapy at University Hospitals Leuven, working with Hendrik Van Poppel, MD, and colleagues. Dr. Budiharto presented the results of the current study at the European Cancer Organisation and European Society for Medical Oncology multidisciplinary congress here.

The population was tested for heterogeneity of patient age and tumor parameters (preoperative PSA, Gleason score, T stage, extracapsular extension, surgical margins, capsular invasion, lymphatic invasion, and vascular invasion), then divided into four homogeneous subgroups based on status (+ or –) of lymphovascular invasion (LVI) and surgical margins (SM). One group contained heterogeneities (SM–/LVI–) that favored salvage RT (lower T stage, less extracapsular extension, and less capsular invasion).

Biochemical disease-free survival (BDFS) was calculated from date of surgery and from end of RT for each subgroup. In three of the four patient groups, salvage RT was a significant predictor of decreased BDFS from the date of surgery and end of RT, Dr. Budiharto reported. In the SM–/LM+ subset, the lack of significant predictors of BDFS was probably due to the small number of patients (34) in this group, he suggested.

From the end of RT, the hazard ratios were:

From the end of surgery, the hazard ratios were:

Adjuvant RT benefit 'very clear'

The 5-year BDFS after prostatectomy was significantly improved by adjuvant RT in some, but not all groups. For the SM–/LVI– subgroup, BDFS was 87% with adjuvant RT versus 65% with salvage RT. For the SM+/LVI+ subgroup, it was 90% for adjuvant RT versus 70% for salvage RT, he said.

"The timing of radiotherapy remains controversial because of the lack of randomized data," Dr. Budiharto said. "But in the absence of this, our retrospective study shows the benefit to be very clear. No subgroups were identified that benefited from early salvage RT. Immediate adjuvant RT for cancer with high-risk features in the specimen significantly reduces the risk of long-term biochemical progression."

He noted that the possibility of over-treatment is often cited as a reason not to use adjuvant RT; however, the incidence of late grade 3 or 4 genitourinary and gastrointestinal toxicity in this population was "acceptable and low."

Commenting from the audience, Chris Parker, MD, of Royal Marsden Hospital in Sutton, Surrey, UK, suggested the conclusion is premature. "In the UK, in Canada, and in most of the U.S., I think the interpretation of these data might be the opposite," Dr. Parker offered, emphasizing that only a randomized trial-such as the Radiotherapy and Androgen Deprivation in Combination after Local Surgery trial, for which Dr. Parker is an investigator-can truly inform this treatment question.

"The current data just strengthen the case for a randomized controlled trial," Dr. Parker said.