Epic fail.

So, after you’ve treated your salvage prostate patients, do you ever wonder, “how did these trials actually define a second biochemical failure?” That’s a great question given the therapeutic implications of the answer. In the above trial, it was a PSA ≥0.2 above the post-radiation nadir, as it was in the Stephenson nomogram. In that large salvage radiation dose response study above, second biochemical failure was defined as a post-radiation PSA >0.2 with a second confirmatory PSA >0.2, or a single PSA >0.4. The Shipley RTOG 9601 trial used a complex algorithm of 0.5 for those with an undetectable nadir, 0.3 above a detectable nadir, or 0.5 above entry PSA if it never dropped. The GETUG-AFU 16 trial used a PSA >0.5 above nadir. And SPPORT is where things really get interesting. They used the Phoenix definition of nadir + 2.0 that we’re all accustomed to for intact prostate. Buried in the study protocol rationale is an analysis of over 500 salvage prostate patients that shows the 2.0 PSA cut-point has the highest sensitivity, specificity, and positive predictive value for clinical progression. Confused yet? TBL: On first thought, a low threshold for second PSA failure makes sense, but a higher threshold that is more closely associated with clinical progression probably makes more sense when deciding when to initiate subsequent lines of therapy. | QuadShot 2019