Prostate-Specific Antigen Level at the Time of Salvage Therapy After Radical Prostatectomy for Prostate Cancer and the Risk of Death (2023, International Study, Full Text)
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Key ObjectiveCan delaying salvage radiation therapy after radical prostatectomy for prostate cancer in men with one high-risk factor (prostatectomy [p] T3/4 or pGleason score 8-10) to obtain a prostate-specific membrane antigen positron emission tomography scan that will be covered by insurers and also have a higher positive predictive value lead to an increased risk of death?
Knowledge GeneratedWaiting to deliver salvage radiation therapy up until a prostate-specific antigen (PSA) level of 0.25 ng/mL was not associated with an increased risk of all-cause mortality; however, this was not true for PSA levels above 0.25 ng/mL.
Relevance Initiating salvage radiotherapy postprostatectomy before the PSA exceeds 0.25 ng/mL is made clearer in this report. With wider use of ultrasensitive PSA in high-risk individuals, individuals can move to salvage therapies before novel imaging can identify sites of persistent disease.
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ABSTRACT
PURPOSEBoth the performance characteristics of prostate-specific membrane antigen positron emission tomography and insurance approval improves with increasing prostate-specific antigen (PSA) level causing some physicians to delay post-radical prostatectomy salvage radiation therapy (sRT) after PSA failure. Yet, it is unknown for men with at most one high-risk factor (ie, pT3/4 or prostatectomy [p] Gleason score 8-10) whether a PSA level exists above which initiating sRT is associated with increased all-cause mortality (ACM)-risk and was investigated.
METHODSUsing a multinational database of 25,551 patients with pT2-4N0 or NXM0 prostate cancer, multivariable Cox regression analysis evaluated whether an association with a significant increase in ACM-risk existed when sRT was delivered above a prespecified PSA level beginning at 0.10 ng/mL and in 0.05 increments up to 0.50 ng/mL versus at or below that level. The model was adjusted for age at and year of radical prostatectomy, established prostate cancer prognostic factors, institution, and the time-dependent use of androgen deprivation therapy.
RESULTSAfter a median follow-up of 6.00 years, patients who received sRT at a PSA level >0.25 ng/mL had a significantly higher ACM-risk (AHR, 1.49; 95% CI, 1.11 to 2.00; P = .008) compared with men who received sRT when the PSA was ≤0.25 mg/mL. This elevated ACM-risk remained significant for all PSA cutpoints up to 0.50 ng/mL but was not significant at PSA cutpoint values below 0.25 ng/mL.
CONCLUSIONAmong patients with at most one high-risk factor, initiating sRT above a PSA level of 0.25 ng/mL was associated with increased ACM-risk."
(See the Full Text, including the Discussion and Tables.)
Note: "Therefore, patients included in this study could have at most one high-risk factor (ie, pGleason score 8-10 or pT3 or pT4) and needed to have achieved an undetectable PSA after RP."I'm seeing other studies and expert interviews that reinforce the point make here: "
With wider use of ultrasensitive PSA in high-risk individuals, individuals can move to salvage therapies before novel imaging can identify sites of persistent disease." Such results may lead to a revision in the standard of care, that still considers treatment a little above PSA of 0.25 to be "early SRT"
Djin