Abstract
PurposeOne of the characteristics of Prostate-Specific Antigen (PSA) is PSA slope. It is the rate of diminishing PSA marker over time after radiotherapy (RT) in prostate cancer (PC) patients. The purpose of this study was to evaluate the relationship between increasing RT doses and PSA slope as a potential surrogate for PC recurrence.Patients and MethodsThis retrospective study was conducted on PC patients who were treated by radiotherapy in the Cancer Institute of Iran during 2007–2012. By reviewing the records of these patients, the baseline PSA measurement before treatment (iPSA), Gleason score (GS), clinical T stage (T. stage), and periodic PSA measurements after RT and the total radiation dose received were extracted for each patient separately. We used a Bayesian dose-response model, analysis of variance, Kruskal–Wallis test, Kaplan–Meier product-limit method for analysis. Probability values less 0.05 were considered statistically significant.ResultsBased on the D’Amico risk assessment system, 13.34% of patients were classified as “Low Risk”, 51.79% were “Intermediate Risk”, and 34.87% were “High Risk”. In terms of radiation doses, 12.31% of the patients received fewer than 50 Gy, 15.38% received 50 to 69 Gy, 61.03% received 70 Gy, and 11.28% received more than 70 Gy. The PSA values decreased after RT for all dose levels. The slope of PSA changes was negative for 176 of 195 patients. By increasing the dosage of radiation, the PSA decreased but these changes were not statistically significant (p = 0.701) and PSA slope as a surrogate end point cannot met the Prentice’s criteria for PC recurrence.ConclusionSignificant changes in the dose-response relationship were not observed when the PSA slope was considered as the response criterion. Therefore, although the absolute value of the PSA decreased with increasing doses of RT, the relationship between PSA slope changes and increasing doses was not clear and cannot be used as a reliable response surrogate endpoint.
Highlights
Prostate cancer is an important health problem in men (Esfahani, Ataei & Panjehpour, 2014; Wilt & Ahmed, 2013)
Rising Prostate-Specific Antigen (PSA) was considered in these definitions (Takamiya et al, 2003) but PSA slope was used as a continuous variable or categorized outcome for determining disease-free survival in a few studies
The slope of PSA changes was negative for 176 patients, meaning that for most of the patients, the overall trend of PSA trajectory was descending
Summary
Prostate cancer is an important health problem in men (Esfahani, Ataei & Panjehpour, 2014; Wilt & Ahmed, 2013). Radiotherapy plays an essential role in the treatment of prostate cancer patients Both the PSA amount and its changes over time, including velocity, density, and doubling time, are important in assessing response to RT (D’Amico et al, 2003; Molenberghs et al, 2002). Some of PSA metrics (e.g., PSA velocity greater than 1.5 ng/ml/yr and PSA doubling time 12 months) are not surrogate endpoint (Collette, Buyse & Burzykowski, 2007; Halabi et al, 2013; Valicenti et al, 2006) Another of these changes over time is the PSA slope. They used a linear mixed model for prediction of PSA evolution in three phases after RT. Takamiya et al (2003) found that a zero PSA slope in post treatment PSA supports cure of patients with long-term follow up after RT, but there are few studies that demonstrated the surrogacy of PSA slope for CF end point
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