For some men, delaying salvage therapy after prostate cancer surgery boosts mortality risk
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Key takeaways:
- Delaying salvage radiotherapy until reaching a PSA level greater than 0.25 ng/mL increased subsequent mortality by nearly 50%.
- Mortality risk remained significantly higher across PSA levels up to 0.5 ng/mL.
Delaying salvage radiation therapy after radical prostatectomy for men with just one high-risk factor for prostate cancer recurrence may significantly increase risk for all-cause mortality, a study in Journal of Clinical Oncology showed.
Researchers found an approximately 50% increase in mortality risk associated with salvage radiation therapy initiation at a PSA level of higher than 0.25 ng/mL compared with a PSA of 0.25 ng/mL or less.
Background
Prostate-specific membrane antigen (PSMA) PET has been used to improve detection of prostate cancer recurrence after surgery but is typically covered by insurance at a PSA level above 0.2 ng/mL. This coupled with evidence that PSMA is more accurate at PSA levels above 0.3 ng/mL has led some clinicians to delay imaging among men with one postsurgical risk factor until the threshold is met, according to Anthony V. D’Amico, MD, PhD, chief of genitourinary radiation oncology at Dana-Farber Brigham Cancer Center.
“But we also know that recurrence is defined as a PSA level of 0.1 ng/mL, and certainly no more than 0.2 ng/mL, so we wondered if waiting until a higher threshold was putting patients at risk for subsequent metastasis or would make our salvage treatments less effective if we waited too long,” he told Healio.
Methodology
D’Amico and colleagues conducted a retrospective study of men with no more than one high-risk factor who underwent radical prostatectomy to determine whether there are PSA levels for the initiation of salvage radiation therapy that correspond to increased risk for all-cause mortality.
The study cohort included 25,551 consecutive patients (median age, 64 years; interquartile range, 59-79) who underwent prostatectomy T2-4N0 or NXM0 PC between June 15, 1990, and June 19, 2020, at University Hospital Hamburg-Eppendorf in Germany or University of California, San Francisco.
Researchers employed multivariate Cox regression analysis to evaluate any association between increased all-cause mortality risk and delivery of salvage radiation therapy at prespecified PSA levels in increments of 0.05 ng/mL beginning at 0.1 ng/mL and ending at 0.5 ng/mL.
Investigators also conducted an adjusted analysis that accounted for age at prostatectomy, year of prostatectomy, prognostic factors, institution and time-dependent use of androgen deprivation therapy.
Median follow-up was 6 years.
Key findings
Researchers reported significantly higher all-cause mortality risk among men who received salvage radiotherapy after radical prostatectomy at a PSA level greater than 0.25 ng/mL compared with those who received salvage therapy at a PSA level of 0.25 ng/mL or less (adjusted HR = 1.49; 95% CI, 1.11-2).
All-cause mortality risk remained significantly higher across all PSA cutoff points up to 0.5 ng/mL, according to investigators. Significantly elevated mortality risk waned at cutoff values below 0.25 ng/mL.
Clinical implications
The increased mortality risk applies to men who have a single risk factor after surgery and not those who have more than one risk factor, including extension of the cancer beyond the prostate. These patients should go on to receive salvage hormonal and radiation therapy before the PSA even becomes measurable, D’Amico said.
The results show a clear cutoff of 0.25 ng/mL, a rarity in medical research, according to D’Amico.
“There is a consistent 50% increased risk past that point,” he told Healio.
D’Amico advised clinicians to order PSMA-PET scans before a PSA level of 0.25 ng/mL.
“If it’s denied, then get an MRI and a bone scan and proceed with salvage therapy before the PSA gets to 0.25 ng/mL,” he said. “If you wait until 0.3 ng/mL, then you’re putting some people at increased risk [for] dying, losing their chance for a cure.”
For more information:
Anthony V. D’Amico, MD, PhD, can be reached at Dana-Farber Brigham Cancer Center, 450 Brookline Ave., Boston, MA 02115; e-mail: adamico@bwh.harvard.edu.
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