Does Treatment Duration Affect Outcome After Radiotherapy for Prostate Cancer?

Abstract

Purpose-The protraction of external beam radiotherapy (RT) time is detrimental in several disease sites. In prostate cancer, the overall treatment time can be considerable, as can the potential for treatment breaks. We evaluated the effect of elapsed treatment time on outcome after RT for prostate cancer.Methods and Materials-Between April 1989 and November 2004, 1,796 men with prostate cancer were treated with RT alone. The nontreatment day ratio (NTDR) was defined as the number of nontreatment days divided by the total elapsed days of RT. This ratio was used to account for the relationship between treatment duration and total RT dose. Men were stratified into low risk (n = 789), intermediate risk (n = 798), and high risk (n = 209) using a single-factor model. Results-The 10-year freedom from biochemical failure (FFBF) rate was 68% for a NTDR <33% vs. 58% for NTDR ≥33% (p = 0.02; BF was defined as a prostate-specific antigen nadir + 2 ng/mL). In the low-risk group, the 10-year FFBF rate was 82% for NTDR <33% vs. 57% for NTDR ≥33% (p = 0.0019). The NTDR was independently predictive for FFBF (p = 0.03), in addition to T stage (p = 0.005) and initial prostate-specific antigen level (p < 0.0001) on multivariate analysis, including Gleason score and radiation dose. The NTDR was not a significant predictor of FFBF when examined in the intermediate-risk group, high-risk group, or all risk groups combined.Conclusions-A proportionally longer treatment duration was identified as an adverse factor in low-risk patients. Treatment breaks resulting in a NTDR of ≥33% (e.g., four or more breaks during a 40-fraction treatment, 5 d/wk) should be avoided.

Moderate Hypofractionated Protracted Radiation Therapy and Dose Escalation for Prostate Cancer: Do Dose and Overall Treatment Time Matter?

“…Recent studies have suggested, however, a clinically significant repopulation effect in patients with low-risk and intermediate-risk prostate cancer with an accelerated repopulation occurring at 4 to 5 weeks and an effective clonogen doubling time of 12 days (31,32). For these patients, an OTT longer than 5 to 6 weeks may influence the outcome, especially if they are treated with suboptimal doses.…”

Factors associated with diagnostic and treatment intervals for prostate cancer in Queensland, Australia: a large cohort study

“…The evidence for an association between clinical outcomes and time intervals to diagnosis and/or treatment is inconsistent, with some studies showing no association [4][5][6] and others finding that longer diagnostic or treatment intervals were associated with lower recurrence-free survival [7][8][9]. These latter studies were, however, inconsistent as to whether the impact was limited to low-risk or high-risk patients.…”

Sensitivity Analysis of Parameters in Linear-Quadratic Radiobiologic Modeling

“…Prostate tumors are unique among tumors, having low a/b ratios of 2 to 3 Gy like slowly proliferating normal tissues. Prostate tumors have the slowest cell doubling time of any human tumor, 42 days (17), and have shown evidence that overall treatment time does not reduce tumor control unless it exceeds 9 or 10 weeks (18,19). All these types of slowly proliferating tissue respond as if their a/b ratios are in the region of 2 or 3 Gy.…”

“…Two relatively recent publications also report a deleterious effect of prolonged overall time, but not until after more than 9 weeks (18) or 10 weeks (19).…”