Presentation Authors: Firas Abdollah*, Deepansh Dalela, Akshay Sood, Sohrab Arora, Hoang Tang, Jacob Keeley, Shaheen Alanee, Craig G Rogers, James Peabody, Mani Menon, Detroit, MI
Introduction: To evaluate the potential impact of lead-time bias on the reported beneficial role of early salvage radiotherapy (sRT), defined as delivering radiation at a relatively low pre-sRT prostate-specific antigen (PSA) value, in treating prostate cancer patients with biochemical recurrence after radical prostatectomy (RP).
Methods: All available demographic, tumor-specific, and overall survival data from 760 men who participated in the RTOG 9601 trial were extracted using the Project Data Sphere platform. Patients were stratified based on pre-sRT PSA ( < 0.7 [n=405], 0.7-1.5 [n=237], and >1.5-4.0 ng/mL [n=118]) as reported in the original trial. Cox regression analysis assessed the impact of pre-sRT PSA on overall mortality, after controlling for covariates. To ascertain the role of lead-time bias, survival time zero was set to the time of (1) initiation of sRT, and (2) RP.
Results: There were no statistically significant differences amongst men within the three groups, except for a greater proportions of African-American patients and men with post-RP PSA nadirs ï‚³0.5 ng/mL within the higher pre-sRT PSA groups. For men with pre-sRT PSA < 0.7, 0.7-1.5, and >1.5-4 ng/mL, estimated 15-year overall mortality was 39%, 45%, and 50%, respectively (p=0.005) when calculated from time since sRT, and 23%, 29%, and 36% respectively (p=0.08) when assessed from time since RP. On multivariable regression analyses, pre-sRT PSA >1.5-4.0 ng/mL was significantly associated with overall mortality only when measured from time of initiation of sRT (HR 1.61, 95% confidence interval [CI] 1.13-2.28; p=0.008), but not from time since RP (HR 1.24, 95% CI 0.87-1.76; p=0.2).
Conclusions: Our findings suggest that the putative survival benefit with early sRT instituted at lower PSA thresholds is mitigated when measured from time since surgery, highlighting the role of lead-time bias. These findings need further validation given their significant clinical implications.