Change Determinants In PSA Over Time - Its Association With Recurrence After External Beam Radiation Therapy For Prostate Cancer In 5 Large Cohorts

Main Category: Prostate / Prostate Cancer
Also Included In: Urology / Nephrology;  Radiology / Nuclear Medicine;  Cancer / Oncology
Article Date: 26 Dec 2008 - 1:00 PDT

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UroToday.com - In the November 1, 2008 issue of International Journal of Radiation Oncology, Biology, Physics, Dr. Cécile Proust-Lima and colleagues presented a linear mixed model to construct patient PSA profiles after radiotherapy (XRT) for prostate cancer (CaP). The included XRT data from 5 patient cohorts where men with CaP were treated for clinically localized disease. Two or 3-dimensional XRT was given to the prostate and seminal vesicles and whole-pelvic radiotherapy was not routinely performed. Prognostic factors evaluated included Gleason score, T-stage, pre-treatment initial PSA (iPSA), age and XRT dosage.

Evolution of PSA after XRT was analyzed by linear mixed model (LMM) with 3 components: post-therapy PSA at the end of XRT (ptPSA), short-term evolution in the first year after XRT (f1(t)), and the long-term evolution denoted as f2(t). Once the LMM was defined, a Cox proportional hazards regression model with time-varying covariates was used to assess the association of pre-treatment prognostic factors and post-treatment pattern of PSA with the time to recurrence of CaP after XRT.

A total of 4,247 patients were analyzed and 339 (12.2%) had clinical recurrences. The median number of PSA measurements was 9. Regarding PSA pattern and its determinants, for ptPSA only iPSA was of statistical significance with higher pretreatment PSA levels corresponding to higher post-treatment PSA levels. iPSA and T-stage were significantly associated with the short-term PSA decline after XRT. iPSA, T-stage and Gleason score all had higher values, corresponding to higher rates of long-term PSA rise. Regarding risk of recurrence, both higher current PSA levels and the rate of PSA change were highly significant in predicting clinical failure. Men with T-stage 3 or 4 had a 39% higher risk of clinical recurrence compared with stage T1 or T2 patients. Men with a Gleason score of 7 had a 62% higher risk of recurrence compared with those having a Gleason score <7. For each unit increase of log PSA, the risk of clinical recurrence decreased by 21%.

Evaluation of other factors on disease progression indicated that higher levels of total XRT dose were significantly associated with lower ptPSA levels and lower rates of long-term PSA growth. Age was significantly associated with ptPSA, but not with the subsequent pattern of PSA. Age was also associated with the risk of clinical recurrence regardless of the PSA pattern and other prognostic factors. A 10-year younger patient with similar other variables had a 36% higher risk of clinical recurrence.

Proust-Lima C, Taylor JM, Williams SG, Ankerst DP, Liu N, Kestin LL, Bae K, Sandler HM
Int J Radiat Oncol Biol Phys. 2008 Nov 1;72(3):782-91.
doi:10.1016/j.ijrobp.2008.01.056

Written by UroToday.com Contributing Editor Christopher P. Evans, MD, FACS

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