Timing of biochemical failure and distant metastatic disease for low-, intermediate-, and high-risk prostate cancer after radiotherapy

Peter B. Morgan, Alexandra L. Hanlon, Eric M. Horwitz, Mark K. Buyyounouski, Robert G. Uzzo, Alan Pollack

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

BACKGROUND. 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. METHODS. 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. RESULTS. 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. CONCLUSIONS. 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.

Original languageEnglish
Pages (from-to)68-80
Number of pages13
JournalCancer
Volume110
Issue number1
DOIs
StatePublished - Jul 1 2007
Externally publishedYes

Fingerprint

Prostatic Neoplasms
Radiotherapy
Radiation Oncology
Neoplasm Metastasis
Neoplasm Micrometastasis
Conformal Radiotherapy
Group Processes
Androgens
Consensus
Multivariate Analysis

Keywords

  • Biochemical control
  • Neoplasm metastasis
  • Outcome
  • Prognostic factors
  • Prostate carcinoma
  • Radiotherapy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Timing of biochemical failure and distant metastatic disease for low-, intermediate-, and high-risk prostate cancer after radiotherapy. / Morgan, Peter B.; Hanlon, Alexandra L.; Horwitz, Eric M.; Buyyounouski, Mark K.; Uzzo, Robert G.; Pollack, Alan.

In: Cancer, Vol. 110, No. 1, 01.07.2007, p. 68-80.

Research output: Contribution to journalArticle

Morgan, Peter B. ; Hanlon, Alexandra L. ; Horwitz, Eric M. ; Buyyounouski, Mark K. ; Uzzo, Robert G. ; Pollack, Alan. / Timing of biochemical failure and distant metastatic disease for low-, intermediate-, and high-risk prostate cancer after radiotherapy. In: Cancer. 2007 ; Vol. 110, No. 1. pp. 68-80.
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abstract = "BACKGROUND. 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. METHODS. 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. RESULTS. 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. CONCLUSIONS. 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.",
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T1 - Timing of biochemical failure and distant metastatic disease for low-, intermediate-, and high-risk prostate cancer after radiotherapy

AU - Morgan, Peter B.

AU - Hanlon, Alexandra L.

AU - Horwitz, Eric M.

AU - Buyyounouski, Mark K.

AU - Uzzo, Robert G.

AU - Pollack, Alan

PY - 2007/7/1

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N2 - BACKGROUND. 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. METHODS. 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. RESULTS. 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. CONCLUSIONS. 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.

AB - BACKGROUND. 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. METHODS. 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. RESULTS. 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. CONCLUSIONS. 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.

KW - Biochemical control

KW - Neoplasm metastasis

KW - Outcome

KW - Prognostic factors

KW - Prostate carcinoma

KW - Radiotherapy

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