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Timing of biochemical failure and distant metastatic disease for low-, intermediate-, and high-risk prostate cancer after radiotherapy†
Article first published online: 22 MAY 2007
Copyright © 2007 American Cancer Society
Volume 110, Issue 1, pages 68–80, 1 July 2007
How to Cite
Morgan, P. B., Hanlon, A. L., Horwitz, E. M., Buyyounouski, M. K., Uzzo, R. G. and Pollack, A. (2007), Timing of biochemical failure and distant metastatic disease for low-, intermediate-, and high-risk prostate cancer after radiotherapy. Cancer, 110: 68–80. doi: 10.1002/cncr.22755
The contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute or Varian Medical Systems.
- Issue published online: 15 JUN 2007
- Article first published online: 22 MAY 2007
- Manuscript Accepted: 16 MAR 2007
- Manuscript Revised: 25 FEB 2007
- Manuscript Received: 14 DEC 2006
- National Cancer Institute. Grant Numbers: CA-006927, CA101984-01
- Varian Medical Systems, Palo Alto, California
- prostate carcinoma;
- prognostic factors;
- biochemical control;
- neoplasm metastasis
The relation of prostate cancer risk-group stratification and the timing of biochemical failure (BF) and distant metastasis (DM) is not well defined. The authors hypothesized that early failures due to subclinical micrometastasis at presentation could be differentiated from late failures due to local persistence.
A total of 1833 men with clinically localized prostate cancer treated with 3D-conformal radiotherapy with or without short-term androgen deprivation were retrospectively analyzed. By using American Society for Therapeutic Radiology and Oncology (ASTRO) and Phoenix (Nadir+2) definitions (developed at the ASTRO-RTOG [Radiation Therapy Oncology Group] consensus meeting, Phoenix, Arizona, January 21, 2005), the interval hazard rates of BF and DM were determined for men with low-risk, intermediate-risk, and high-risk disease.
Median follow-up was 67 months. Multivariate analysis showed that increasing risk group was independently associated with higher ASTRO BF (P < .0001) and Nadir+2 BF (P < .0001). The preponderance (87%) of ASTRO BF occurred ≤4 years after radiotherapy, whereas Nadir+2 BF was more evenly spread over Years 1–12, with 43% at >4 years. The hazard of Nadir+2 BF persisted in Years 8–12 in all risk groups. The interval hazard function for DM appeared to be biphasic (early peak followed by a drop and late increase) for intermediate-risk and high-risk patients, but no distinct early wave was evident for low-risk patients.
Because of backdating, ASTRO BF underestimates late BF. Local persistence of disease is suggested by delayed Nadir+2 BF and subsequent late DM in every risk group. The paucity of early DM among those with low-risk tumors supports the hypothesis that occult micrometastases contributed to the early wave. Cancer 2007. © 2007 American Cancer Society.