Cyclooxygenase 2 (COX-2) expression in locally advanced prostate cancer: secondary analysis of radiation therapy oncology group (RTOG) 86-10

Purpose Diabetes is associated with lower risk of prostate cancer. Most men with diabetes are obese, and obesity is associated with greater prostate cancer mortality. Whether diabetes influences outcomes after prostate cancer diagnosis is unknown. Patients and Methods We assessed the relationship between prevalent diabetes and mortality using data from Radiation Therapy Oncology Group Protocol 92-02, a large randomized trial of men (N = 1,554) treated with radiation therapy and short-term versus long-term adjuvant goserelin for locally advanced prostate cancer. Regression and proportional hazard models were performed to evaluate relationships between prevalent diabetes and all-cause mortality, prostate cancer mortality, and non–prostate cancer mortality. Covariates included age, race, tumor stage, Gleason score, prostate-specific antigen, weight, and treatment arm. Results There were a total of 765 deaths; 210 (27%) were attributed to prostate cancer. In univariate analyses, prevalent diabetes was associated with greater all-cause mortality and non–prostate cancer mortality but not prostate cancer mortality. After controlling for other covariates, prevalent diabetes remained significantly associated with greater all-cause mortality and non–prostate cancer mortality (hazard ratio [HR] = 2.12; 95% CI, 1.69 to 2.66; P < .0001) but not prostate cancer mortality (HR = 0.80; 95% CI, 0.51 to 1.25; P = .34). In contrast, weight was associated with greater prostate cancer mortality (HR = 1.77; 95% CI, 1.22 to 2.55; P = .002) but not all-cause or non–prostate cancer mortality. Conclusion Weight but not prevalent diabetes is associated with greater prostate cancer mortality in men receiving combined modality treatment for locally advanced disease. These observations suggest that the association between obesity and greater prostate cancer mortality is mediated by mechanism(s) other than the characteristic metabolic alterations of diabetes.

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Economic analysis of a phase III clinical trial evaluating the addition of total androgen suppression to radiation versus radiation alone for locally advanced prostate cancer (Radiation Therapy Oncology Group protocol 86-10)

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/j.ijrobp.2005.03.010 ◽

2005 ◽

Vol 63 (3) ◽

pp. 788-794 ◽

Cited By ~ 23

Author(s):

Andre Konski ◽

Eric Sherman ◽

Murray Krahn ◽

Karen Bremner ◽

J. Robert Beck ◽

...

Keyword(s):

Prostate Cancer ◽

Clinical Trial ◽

Advanced Prostate Cancer ◽

Locally Advanced ◽

Radiation Therapy Oncology Group ◽

Phase Iii ◽

Oncology Group ◽

Locally Advanced Prostate Cancer ◽

Phase Iii Clinical Trial ◽

Androgen Suppression

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Prognostic Value of p16 in Locally Advanced Prostate Cancer: A Study Based on Radiation Therapy Oncology Group Protocol 9202

Journal of Clinical Oncology ◽

10.1200/jco.2006.08.4152 ◽

2007 ◽

Vol 25 (21) ◽

pp. 3082-3089 ◽

Cited By ~ 39

Author(s):

Arnab Chakravarti ◽

Michelle DeSilvio ◽

Min Zhang ◽

David Grignon ◽

Seth Rosenthal ◽

...

Keyword(s):

Prostate Cancer ◽

Prognostic Value ◽

Advanced Prostate Cancer ◽

Locally Advanced ◽

Radiation Therapy Oncology Group ◽

Distant Metastases ◽

Oncology Group ◽

Locally Advanced Prostate Cancer ◽

Low Levels ◽

P16 Expression

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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