Evaluating the impact of lead-time bias on the observed efficacy of early salvage radiation therapy in prostate cancer: A post-hoc analysis of the RTOG 9601 trial

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Conference Proceeding

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Eur Urol Suppl


Introduction & Objectives: 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).

Materials & 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 (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 30.5 ng/mL within the higher pre-sRT PSA groups. For men with pre-sRT PSA1.5-4 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.





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