Impact of Ultrahigh Baseline PSA Levels on Biochemical and Clinical Outcomes in Two Radiation Therapy Oncology Group Prostate Clinical Trials

Abstract

Purpose To assess ultra-high (UH; PSA ≥ 50 ng/ml) patient outcomes compared to other high-risk patients and to identify outcome predictors. Methods and Materials PCP from two Phase III RTOG clinical trials (9202 and 9413) were divided into two groups; high-risk patients with and without UH baseline PSA level. Predictive variables included age, Gleason score, clinical T stage, KPS, and treatment arm. Outcomes included overall survival (OS), distant metastasis (DM), and biochemical failure (BF). Unadjusted and adjusted hazard ratios (HRs) were calculated using either the Cox or Fine and Gray’s regression model with associated 95% confidence intervals (CI) and p-values. Results There were 401 in the UH PSA and 1792 in the non-UH PSA PCP out of 2193 high risk PCP. PCP with UH PSA was found to have inferior OS (HR 1.19, 95% CI 1.02-1.39, p-value=0.02), DM (HR 1.51, 95% CI 1.19-1.92, p-value=0.0006), and BF (HR 1.50, 95% CI 1.29-1.73, p-value <0.0001) when compared to other high-risk PCP. In the UH cohort, PSA was found to be a significant factor for the risk of DM (HR 1.01, 95% CI 1.001-1.02) but not OS and BF. Gleason grade 8-10 was found to consistently predict for poor OS, DM, and BF outcomes (with HR estimates ranging from 1.41 to 2.36) in both the high-risk cohort and UH cohort multivariable analyses. Conclusions UH PSA levels at diagnosis are related with detrimental changes in OS, DM, and BF. All three outcomes can be modelled by various combinations all predictive variables tested.

Practice Patterns and Outcomes Among Patients With N0M0 Prostate Cancer and a Very High Prostate-Specific Antigen Level

“…Our results are consistent with the work of others [17][18][19][20][21] showing that, although a very high PSA level portends a poorer prognosis compared with other N0M0 prostate cancer, these presentations may still frequently be curable. Clinical trials establishing the curative role of locoregional treatment and adjuvant hormonal therapy have included men with PSA levels of 50 to 160 ng/mL, 5,22,23 although these studies were not designed to determine whether the subpopulation of men with a very high PSA level could benefit from locoregional treatment.…”

“…A pooled analysis of 2 RTOG trials suggested that patients with a PSA level $50 ng/mL have a higher adjusted rate of biochemical failure, distant metastasis, and mortality compared with other high-risk patients, but the effect size was modest, with similar unadjusted rates of 7-year OS compared with those with a PSA level ,50 ng/mL (64.3% vs 68.0%); there was no comparison with a cohort of node-positive patients. 17 A Canadian registry study showed that among 207 patients with a PSA level $100 ng/mL, radiation therapy was associated with improved 5-year OS compared with ADT alone (68% vs 40%). 18 Several institutional studies have similarly shown good long-term outcomes for patients with very high PSA levels, albeit inferior to outcomes for patients with lower PSA levels.…”

Predictors of survival in prostate cancer patients with bone metastasis and extremely high prostate-specific antigen levels

“… 1,5 In localized PCa, serum PSA has been demonstrated to correlate with the pathological stage, Gleason score, and the probability of organ-confined disease 7,8 ; whereas, in metastatic PCa, PSA has been shown to reflect the disease burden, and its post-hormone therapy response serves as a predictor of overall survival. 9 However, in a number of previous population-based observational studies, a PSA level >50 ng/mL was observed to correlate with extreme-risk patients, who showed a worse response to treatment and survival outcome than other high risk patients. 7,9,10 Therefore, it is conceivable that the high risk population includes a subset of patients who are at an extreme risk for disease progression and mortality.…”

Do Prostate Cancer Patients With Markedly Elevated PSA Benefit From Radiation Therapy?

“…Although ultra-high PSA had a negative impact on overall survival, distant metastases, and biochemical failure, the authors did not view it as a contraindication to local radical therapy. 28 Likewise, Alexander 29 reported good outcomes for patients at a single institution with PSA > 40 ng/mL treated with radiation combined with androgen ablation. Tai et al 10 studied 539 patients listed in the Saskatchewan cancer registry who had a PSAZ50 ng/mL at time of diagnosis.…”