In the Journals

Pre-salvage radiotherapy PSA level may be a prognostic biomarker in prostate cancer

Daniel E. Spratt, MD
Daniel E. Spratt

PSA level prior to salvage radiotherapy may be a prognostic biomarker for clinical outcomes of long-term antiandrogen therapy with salvage radiotherapy among men with prostate cancer, according to results of a secondary analysis of a randomized trial published in JAMA Oncology.

“There are multiple prognostic biomarkers for men [after] prostatectomy, including Gleason score, tumor stage and margin status,” Daniel E. Spratt, MD, Laurie Snow research professor of radiation oncology and associate chair of clinical research at University of Michigan, chair of genitourinary clinical research and director of the spine oncology program at the university’s Rogel Cancer Center, and HemOnc Today Next Gen Innovator, told Healio. “However, pre-salvage radiotherapy (SRT) PSA appears to be one of the strongest prognostic clinical biomarkers, if not the strongest.”

“There are newer gene expression-based molecular biomarkers, and the one with the best evidence and guideline support [after] prostatectomy is the Decipher [GenomeDX Biosciences] 22-gene classifier,” he added. “None of these tests on their own are perfect, but when combined provide highly accurate estimates of a patient’s prognosis.”

Results of the NRG/RTOG9601 study, conducted between 1998 and 2003, showed an association between the addition of long-term antiandrogen therapy to SRT and improved OS. However, hormone therapy is associated with morbidity, and no validated predictive biomarkers exist to determine which men derive the most benefit from treatment.

Spratt and colleagues performed a secondary analysis of the double-blind RTOG9601 study, in which men with a positive surgical margin or pathologic T3 prostate cancer after radical prostatectomy and a pre-SRT PSA level of 0.2 ng/mL to 4 ng/mL had been randomly assigned to SRT in combination with a high-dose nonsteroidal antiandrogen (bicalutamide dosed at 150 mg daily) or placebo.

The secondary analysis included 760 men (median age, 65 years; range, 40-83) with elevated PSA after radical prostatectomy.

OS served as the primary endpoint of the secondary analysis. Distant metastasis, other-cause mortality and grade 3 to grade 5 cardiac and neurologic toxic effects served as secondary endpoints.

Median follow-up of surviving men was 13.1 years for the antiandrogen therapy group and 13 months for the placebo group.

Results showed an association between antiandrogen therapy and an OS benefit among 118 men with a PSA level greater than 1.5 ng/mL (HR = 0.45; 95% CI, 0.25-0.81). Men with a PSA level of 1.5 ng/mL or less (n = 642) did not experience a significant OS benefit (HR = 0.87; 95% CI, 0.66-1.16).

Antiandrogen therapy did, however, confer an OS benefit among 253 men with a PSA level of 0.61 ng/mL to 1.5 ng/mL (HR = 0.61; 95% CI, 0.39-0.94).

Among men with a PSA of 0.6 ng/mL or less who received early SRT (n = 389), researchers observed no improvement in OS (HR = 1.16; 95% CI, 0.79-1.7), an increased hazard for other-cause mortality (subdistribution HR = 1.94; 95% CI, 1.17-3.2) and increased odds for late grade 3 to grade 5 cardiac and neurologic toxic effects (OR = 3.57; 95% CI, 1.09-15.97).

Subgroup analyses can be underpowered and are subject to bias, which served as a limitation to this study.

“Pre-SRT PSA can serve as both a prognostic and predictive serum biomarker to guide hormone therapy use with SRT,” Spratt and colleagues wrote. “Randomized clinical trials are ongoing to determine if molecular biomarkers can further help personalize hormone therapy use in men receiving early SRT.” – by John DeRosier

For more information:

Daniel E. Spratt, MD, can be reached at UH B2 C502, 1500 E Medical Center Drive, Ann Arbor, MI 48109; email: sprattda@med.umich.edu.

Disclosures: Spratt reports personal fees from Blue Earth and Janssen. Please see the study for all other authors’ relevant financial disclosures.

Daniel E. Spratt, MD
Daniel E. Spratt

PSA level prior to salvage radiotherapy may be a prognostic biomarker for clinical outcomes of long-term antiandrogen therapy with salvage radiotherapy among men with prostate cancer, according to results of a secondary analysis of a randomized trial published in JAMA Oncology.

“There are multiple prognostic biomarkers for men [after] prostatectomy, including Gleason score, tumor stage and margin status,” Daniel E. Spratt, MD, Laurie Snow research professor of radiation oncology and associate chair of clinical research at University of Michigan, chair of genitourinary clinical research and director of the spine oncology program at the university’s Rogel Cancer Center, and HemOnc Today Next Gen Innovator, told Healio. “However, pre-salvage radiotherapy (SRT) PSA appears to be one of the strongest prognostic clinical biomarkers, if not the strongest.”

“There are newer gene expression-based molecular biomarkers, and the one with the best evidence and guideline support [after] prostatectomy is the Decipher [GenomeDX Biosciences] 22-gene classifier,” he added. “None of these tests on their own are perfect, but when combined provide highly accurate estimates of a patient’s prognosis.”

Results of the NRG/RTOG9601 study, conducted between 1998 and 2003, showed an association between the addition of long-term antiandrogen therapy to SRT and improved OS. However, hormone therapy is associated with morbidity, and no validated predictive biomarkers exist to determine which men derive the most benefit from treatment.

Spratt and colleagues performed a secondary analysis of the double-blind RTOG9601 study, in which men with a positive surgical margin or pathologic T3 prostate cancer after radical prostatectomy and a pre-SRT PSA level of 0.2 ng/mL to 4 ng/mL had been randomly assigned to SRT in combination with a high-dose nonsteroidal antiandrogen (bicalutamide dosed at 150 mg daily) or placebo.

The secondary analysis included 760 men (median age, 65 years; range, 40-83) with elevated PSA after radical prostatectomy.

OS served as the primary endpoint of the secondary analysis. Distant metastasis, other-cause mortality and grade 3 to grade 5 cardiac and neurologic toxic effects served as secondary endpoints.

Median follow-up of surviving men was 13.1 years for the antiandrogen therapy group and 13 months for the placebo group.

Results showed an association between antiandrogen therapy and an OS benefit among 118 men with a PSA level greater than 1.5 ng/mL (HR = 0.45; 95% CI, 0.25-0.81). Men with a PSA level of 1.5 ng/mL or less (n = 642) did not experience a significant OS benefit (HR = 0.87; 95% CI, 0.66-1.16).

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Antiandrogen therapy did, however, confer an OS benefit among 253 men with a PSA level of 0.61 ng/mL to 1.5 ng/mL (HR = 0.61; 95% CI, 0.39-0.94).

Among men with a PSA of 0.6 ng/mL or less who received early SRT (n = 389), researchers observed no improvement in OS (HR = 1.16; 95% CI, 0.79-1.7), an increased hazard for other-cause mortality (subdistribution HR = 1.94; 95% CI, 1.17-3.2) and increased odds for late grade 3 to grade 5 cardiac and neurologic toxic effects (OR = 3.57; 95% CI, 1.09-15.97).

Subgroup analyses can be underpowered and are subject to bias, which served as a limitation to this study.

“Pre-SRT PSA can serve as both a prognostic and predictive serum biomarker to guide hormone therapy use with SRT,” Spratt and colleagues wrote. “Randomized clinical trials are ongoing to determine if molecular biomarkers can further help personalize hormone therapy use in men receiving early SRT.” – by John DeRosier

For more information:

Daniel E. Spratt, MD, can be reached at UH B2 C502, 1500 E Medical Center Drive, Ann Arbor, MI 48109; email: sprattda@med.umich.edu.

Disclosures: Spratt reports personal fees from Blue Earth and Janssen. Please see the study for all other authors’ relevant financial disclosures.