Validation of a treatment policy for patients with prostate specific antigen failure after three‐dimensional conformal prostate radiation therapy

Abstract

BACKGROUNDThe objective of this report was to present an outcomes validation for the Fox Chase Cancer Center (FCCC) management policy for patients who demonstrate prostate specific antigen (PSA) failure after receiving three‐dimensional conformal radiation therapy (3DCRT).METHODSEligible patients included 248 men with T1–T3N0M0 prostate carcinoma who demonstrated PSA failure (according to the American Society for Therapeutic Radiology and Oncology definition) after completing definitive 3DCRT alone or with androgen deprivation (AD) therapy between May 1989 and November 1997. The primary endpoint evaluated was freedom from distant metastasis (FDM). The secondary endpoints evaluated included cause specific survival (CSS) and overall survival (OS). The variables evaluated in the multivariate analyses (MVA) included initial PSA, Gleason score, T classification, dose, PSA nadir, time to PSA failure, PSA doubling time (PSADT), initial use of AD therapy, and the use of AD therapy upon PSA failure.RESULTSThe 5‐year FDM, CSS, and OS rates for the entire group were 76%, 92%, and 76%, respectively. It was found that four variables were independent predictors of FDM: Gleason score (P = 0.0039), PSA nadir (P = 0.0001), PSADT (P = 0.0001), and the use of AD on PSA failure (P = 0.0001). One hundred forty‐eight men demonstrated a PSADT < 12 months. AD therapy was started in 59 men, and 89 men refused AD therapy and were observed. The use of AD therapy was associated with a significant improvement in the 5‐year FDM rate (57% vs. 78%; P = 0.0026). In the group of men with PSADT < 12 months, the median time to distant failure was significantly longer in the men who received AD therapy (6 months vs. 25 months; P = 0.02). Of the 100 men with a PSADT ≥ 12 months, 89 men were observed, and 11 men received AD therapy. There was no improvement in the 5‐year FDM rate with the use of AD therapy compared with observation (88% vs. 92%, respectively; P = 0.74).CONCLUSIONSThe current results validate the use of PSADT as an indicator of patients who may be observed expectantly or treated with AD therapy for PSA failure after 3DCRT. Prospective trials are needed to define further the optimal treatment for these patients. Cancer 2003;97:1127–33. © 2003 American Cancer Society.DOI 10.1002/cncr.11166

PSA Doubling Time Predicts for the Development of Distant Metastases for Patients Who Fail 3DCRT or IMRT using the Phoenix Definition

“…Independent predictors of distant metastases included PSADT, early salvage ADT, high PSA nadir, and Gleason score. Based on these results, Pinover et al developed an algorithm for the use of salvage ADT in patients with rising PSA based on PSADT, PSA nadir, and Gleason score in which we recommended immediate ADT if the PSADT was <12 months (17). The current study updates and confirms our earlier results with longer follow-up and a larger database reflecting more patients treated with dose-escalation and IMRT.…”

“…For those patients with long PSADT (>12 months), we recommend close follow-up with serial PSA levels (typically every 6 months). We have previously recommended that salvage ADT be offered to all patients with PSADT <12 (17); however, in this study the addition of ADT was not associated with a decreased incidence of distant metastases in patients with PSADT between 6-12 months. For these patients we base the start of ADT on a variety of factors including performance status, age, anxiety and comfort level, and recommend more frequent PSA levels and follow-up visits for those who do not begin ADT.…”

“…Since 1989, it has been our institution's practice to closely observe patients with biochemical failure and PSADT greater than 12 months, while recommending early salvage to those with PSADT less than 12 months. Our institutional experience, published in 2003 (17), validated this practice, demonstrating that men with a PSADT greater than 12 months were unlikely to develop clinical progression, and can most likely be spared immediate androgen deprivation therapy.…”

“…At our institution, radiation dose has increased over time such that patients treated more recently have received higher radiation doses than those treated earlier (41). In this study population, the median radiation dose is 76 Gy (range: 66-84 Gy), up from the median of 74 Gy (range: 61-80 Gy) at the time of Pinover's publication (17). Like Pinover, we were unable to demonstrate a significant relationship between RT dose and FDM.…”

“…A subsequent study by Lee et al (15) found PSADT and interval to biochemical failure to be independent predictors of distant metastases in a cohort of 151 prostate cancer patients with rising PSA after definitive radiation. In 2003, Pinover et al published the results of a study examining 248 patients who experienced biochemical failure according to the original ASTRO definition after treatment with 3DCRT to the prostate at our institution (17). The use of ADT did not have a significant association with 5-year FDM for men with PSADT >12 months (88% vs. 92%, p = 0.74), but did show a significant improvement in men with PSADT <12 months (78% vs. 57%, p = 0.003).…”