Prognostic value of p16 in locally advanced prostate cancer: A study based on Radiation Therapy Oncology Group protocol 9202

Arnab Chakravarti, Michelle DeSilvio, Min Zhang, David Grignon, Seth Rosenthal, Sucha O. Asbell, Gerald Hanks, Howard M. Sandler, Li Yan Khor, Alan Pollack, William Shipley

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Purpose: Deregulation of the retinoblastoma (RB) pathway is commonly found in virtually all known human tumors. p16, the upstream regulator of RB, is among the most commonly affected member of this pathway. In the present study, we examined the prognostic value of p16 expression in men with locally advanced prostate cancer who were enrolled on Radiation Therapy Oncology Group protocol 9202. Patients and Methods: RTOG 9202 was a phase III randomized study comparing long-term (LT) versus short-term (ST) androgen-deprivation therapy (AD). Of the 1,514 eligible cases, 612 patients had adequate tumor material for p16 analysis. Expression levels of p16 were determined by immunohistochemistry (IHC). IHC staining was scored quantitatively using an image analysis system. Results: On multivariate analysis, intact p16 expression was significantly associated with decreased rate of distant metastases (P = .0332) when both STAD and LTAD treatment arms were considered together. For patients with intact (high levels of immunostaining) p16 (mean p16 index > 81.3%), LTAD plus radiotherapy (RT) significantly improved prostate cancer survival (PCS) compared with STAD plus RT (P = .0008) and reduced the frequency of distant metastasis (P = .0069) compared with STAD plus RT. In contrast, for patients with tumors demonstrating p16 loss (low levels of immunostaining, mean p16 index ≤ 81.3%), LTAD plus RT significantly improved biochemical no evidence of disease survival over STAD (P <.0001) primarily by decreasing the frequency of local progression (P = .02), as opposed to distant metastasis, which was the case in the high-p16 cohort. Conclusion: Low levels of p16 on image analysis appear to be associated with a significantly higher risk of distant metastases among all study patients. p16 expression levels also appear to identify patients with locally advanced prostate cancer with distinct patterns of failure after LTAD.

Original languageEnglish (US)
Pages (from-to)3082-3089
Number of pages8
JournalJournal of Clinical Oncology
Volume25
Issue number21
DOIs
StatePublished - Jul 20 2007
Externally publishedYes

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Radiation Oncology
Prostatic Neoplasms
Radiotherapy
Neoplasm Metastasis
Retinoblastoma
Immunohistochemistry
Neoplasms
Survival
Androgens
Multivariate Analysis
Staining and Labeling
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Prognostic value of p16 in locally advanced prostate cancer : A study based on Radiation Therapy Oncology Group protocol 9202. / Chakravarti, Arnab; DeSilvio, Michelle; Zhang, Min; Grignon, David; Rosenthal, Seth; Asbell, Sucha O.; Hanks, Gerald; Sandler, Howard M.; Khor, Li Yan; Pollack, Alan; Shipley, William.

In: Journal of Clinical Oncology, Vol. 25, No. 21, 20.07.2007, p. 3082-3089.

Research output: Contribution to journalArticle

Chakravarti, A, DeSilvio, M, Zhang, M, Grignon, D, Rosenthal, S, Asbell, SO, Hanks, G, Sandler, HM, Khor, LY, Pollack, A & Shipley, W 2007, 'Prognostic value of p16 in locally advanced prostate cancer: A study based on Radiation Therapy Oncology Group protocol 9202', Journal of Clinical Oncology, vol. 25, no. 21, pp. 3082-3089. https://doi.org/10.1200/JCO.2006.08.4152
Chakravarti, Arnab ; DeSilvio, Michelle ; Zhang, Min ; Grignon, David ; Rosenthal, Seth ; Asbell, Sucha O. ; Hanks, Gerald ; Sandler, Howard M. ; Khor, Li Yan ; Pollack, Alan ; Shipley, William. / Prognostic value of p16 in locally advanced prostate cancer : A study based on Radiation Therapy Oncology Group protocol 9202. In: Journal of Clinical Oncology. 2007 ; Vol. 25, No. 21. pp. 3082-3089.
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abstract = "Purpose: Deregulation of the retinoblastoma (RB) pathway is commonly found in virtually all known human tumors. p16, the upstream regulator of RB, is among the most commonly affected member of this pathway. In the present study, we examined the prognostic value of p16 expression in men with locally advanced prostate cancer who were enrolled on Radiation Therapy Oncology Group protocol 9202. Patients and Methods: RTOG 9202 was a phase III randomized study comparing long-term (LT) versus short-term (ST) androgen-deprivation therapy (AD). Of the 1,514 eligible cases, 612 patients had adequate tumor material for p16 analysis. Expression levels of p16 were determined by immunohistochemistry (IHC). IHC staining was scored quantitatively using an image analysis system. Results: On multivariate analysis, intact p16 expression was significantly associated with decreased rate of distant metastases (P = .0332) when both STAD and LTAD treatment arms were considered together. For patients with intact (high levels of immunostaining) p16 (mean p16 index > 81.3{\%}), LTAD plus radiotherapy (RT) significantly improved prostate cancer survival (PCS) compared with STAD plus RT (P = .0008) and reduced the frequency of distant metastasis (P = .0069) compared with STAD plus RT. In contrast, for patients with tumors demonstrating p16 loss (low levels of immunostaining, mean p16 index ≤ 81.3{\%}), LTAD plus RT significantly improved biochemical no evidence of disease survival over STAD (P <.0001) primarily by decreasing the frequency of local progression (P = .02), as opposed to distant metastasis, which was the case in the high-p16 cohort. Conclusion: Low levels of p16 on image analysis appear to be associated with a significantly higher risk of distant metastases among all study patients. p16 expression levels also appear to identify patients with locally advanced prostate cancer with distinct patterns of failure after LTAD.",
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T1 - Prognostic value of p16 in locally advanced prostate cancer

T2 - A study based on Radiation Therapy Oncology Group protocol 9202

AU - Chakravarti, Arnab

AU - DeSilvio, Michelle

AU - Zhang, Min

AU - Grignon, David

AU - Rosenthal, Seth

AU - Asbell, Sucha O.

AU - Hanks, Gerald

AU - Sandler, Howard M.

AU - Khor, Li Yan

AU - Pollack, Alan

AU - Shipley, William

PY - 2007/7/20

Y1 - 2007/7/20

N2 - Purpose: Deregulation of the retinoblastoma (RB) pathway is commonly found in virtually all known human tumors. p16, the upstream regulator of RB, is among the most commonly affected member of this pathway. In the present study, we examined the prognostic value of p16 expression in men with locally advanced prostate cancer who were enrolled on Radiation Therapy Oncology Group protocol 9202. Patients and Methods: RTOG 9202 was a phase III randomized study comparing long-term (LT) versus short-term (ST) androgen-deprivation therapy (AD). Of the 1,514 eligible cases, 612 patients had adequate tumor material for p16 analysis. Expression levels of p16 were determined by immunohistochemistry (IHC). IHC staining was scored quantitatively using an image analysis system. Results: On multivariate analysis, intact p16 expression was significantly associated with decreased rate of distant metastases (P = .0332) when both STAD and LTAD treatment arms were considered together. For patients with intact (high levels of immunostaining) p16 (mean p16 index > 81.3%), LTAD plus radiotherapy (RT) significantly improved prostate cancer survival (PCS) compared with STAD plus RT (P = .0008) and reduced the frequency of distant metastasis (P = .0069) compared with STAD plus RT. In contrast, for patients with tumors demonstrating p16 loss (low levels of immunostaining, mean p16 index ≤ 81.3%), LTAD plus RT significantly improved biochemical no evidence of disease survival over STAD (P <.0001) primarily by decreasing the frequency of local progression (P = .02), as opposed to distant metastasis, which was the case in the high-p16 cohort. Conclusion: Low levels of p16 on image analysis appear to be associated with a significantly higher risk of distant metastases among all study patients. p16 expression levels also appear to identify patients with locally advanced prostate cancer with distinct patterns of failure after LTAD.

AB - Purpose: Deregulation of the retinoblastoma (RB) pathway is commonly found in virtually all known human tumors. p16, the upstream regulator of RB, is among the most commonly affected member of this pathway. In the present study, we examined the prognostic value of p16 expression in men with locally advanced prostate cancer who were enrolled on Radiation Therapy Oncology Group protocol 9202. Patients and Methods: RTOG 9202 was a phase III randomized study comparing long-term (LT) versus short-term (ST) androgen-deprivation therapy (AD). Of the 1,514 eligible cases, 612 patients had adequate tumor material for p16 analysis. Expression levels of p16 were determined by immunohistochemistry (IHC). IHC staining was scored quantitatively using an image analysis system. Results: On multivariate analysis, intact p16 expression was significantly associated with decreased rate of distant metastases (P = .0332) when both STAD and LTAD treatment arms were considered together. For patients with intact (high levels of immunostaining) p16 (mean p16 index > 81.3%), LTAD plus radiotherapy (RT) significantly improved prostate cancer survival (PCS) compared with STAD plus RT (P = .0008) and reduced the frequency of distant metastasis (P = .0069) compared with STAD plus RT. In contrast, for patients with tumors demonstrating p16 loss (low levels of immunostaining, mean p16 index ≤ 81.3%), LTAD plus RT significantly improved biochemical no evidence of disease survival over STAD (P <.0001) primarily by decreasing the frequency of local progression (P = .02), as opposed to distant metastasis, which was the case in the high-p16 cohort. Conclusion: Low levels of p16 on image analysis appear to be associated with a significantly higher risk of distant metastases among all study patients. p16 expression levels also appear to identify patients with locally advanced prostate cancer with distinct patterns of failure after LTAD.

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