Outcomes drop with break in prostate cancer Tx.

LOS ANGELES -- For men with low-risk prostate cancer, skipping more than two sessions of radiotherapy beyond their scheduled weekends off can have long-term consequences, investigators found when they reviewed nearly 1,800 patients treated in 1989-2004 at a single cancer center.

Biochemical control at 5 and 10 years was significantly worse for men who skipped more than 2 days, even though they ultimately completed their treatments, Dr. David J. D'Ambrosio reported at the annual meeting of the American Society for Therapeutic Radiation and Oncology.

The impact of treatment interruptions was significant for the population as a whole, but the disparity was driven by a highly significant difference within the low-risk group. Interruptions had little to no impact in men with medium- or high-risk disease.

At 5 years, the freedom-from-biochemical-failure (FFBF) rate was 90% in patients who skipped the equivalent of more than 2 days for low-risk prostate risk prostate cancer versus 95% in those who took shorter breaks or no breaks. At 10 years, the FFBF rates were 57% and 82%, respectively.

"Our hypothesis for why this was seen in the low-risk group is that the low-risk patients are the ones most likely to have cancer just confined to the prostate. So ... they are the ones who have the most to gain and lose from the local treatment," Dr. D'Ambrosio, a radiation oncology resident at Fox Chase Cancer Center in Philadelphia, said in an interview at the meeting.

He suggested men with medium- or high-risk disease were more likely to have distant metastases that would not be affected by differences in timing of local treatment to the prostate.

Findings of previous studies have conflicted on the question of whether small interruptions in prostate cancer treatment can be harmful, according to Dr. D'Ambrosio. The most recent study (Int. J. Radiat. Oncol. Biol. Phys. 1990;19:561-8) preceded the era of detection by prostate-specific antigen (PSA) levels, leading Dr. D'Ambrosio and his coinvestigators to question whether the previous findings are still relevant.

"If you look at the older papers, they are really [about] a completely different group of prostate cancer patients," he said. "[Today] the doses are higher, the fields are smaller for the most part, and the length of treatment is typically longer."

The new study identified 1,796 men who received 3-D conformal radiation therapy (76%) or intensity-modulated radiation therapy (24%) between April 1989 and November 2004 at Fox Chase. None had androgen deprivation therapy. The median dose was 76 Gy, median patient age was 69 years, and median follow-up was 62 months.

On the basis of Gleason score, pretreatment PSA levels, and tumor stage, the patients were stratified into three groups: high risk (209 patients, 12%), medium risk (798, 44%), and low risk (789, 44%).

To compare the impact of skipping occasional sessions in patients on different radiation doses and schedules, the investigators created a nontreatment days ratio (NTDR). They calculated each patient's NTDR by dividing the total elapsed days during treatment into the number of nontreatment days.

Whereas the number of nontreatment days included weekends, skipped days, and holidays, the total elapsed days during treatment included all scheduled days plus days added on at the end to make up for breaks. For example, a patient on an 8-week regimen takes two long weekends, which results in his skipping 2 days that are added on at the end of treatment. His ratio would be 18 (16 weekend plus 2 skipped) days divided by 58 (56 scheduled length plus 2 added) days, or 31%.

The investigators determined that patients with a ratio of 33% or higher were less likely to maintain long-term biochemical control. "This is the first time [the impact of skipped treatment days] has been shown, and it needs to be repeated before it is taken as dogma," he said.

BY JANE SALODOF MACNEIL

Senior Editor