Predictive models in external beam radiotherapy for clinically localized prostate cancer

Abstract

Predictive models are being used increasingly in effort to allow physician and patient expectations to be aligned with outcomes that are based on available data. Most predictive models for men who receive external beam radiotherapy for clinically localized prostate cancer are based on Gleason score, clinical tumor classification, and prostate-specific antigen (PSA) levels. More sophisticated models also have been developed that incorporate treatment-related variables, such as the dose of radiation and the use of androgen-deprivation therapy. Most of the predictive models applied to prostate cancer were derived using PSA recurrence rates as the major endpoint, but clinical endpoints have been incorporated increasingly into predictive models. Biomarkers also are increasingly being added to predictive models in an effort to strengthen them. The Radiation Therapy Oncology Group (RTOG) has completed studies on a wide range of markers using tissue from 2 phase 3 trials (RTOG 8610 and 9202). To date, preliminary assessments of p53; DNA ploidy; p16/retinoblastoma 1 protein; Ki-67; mouse double-minute p53 binding protein homolog; Bcl-2/Bcl-2-associated X protein; cytosine, adenine, and guanine repeats; cyclooxygenase-2; signal transducer and activator of transcription 3; cytochrome P450 3A4; and protein kinase A have been completed. Although they are not ready for widespread, routine use, there are reasons to believe that future models will combine these markers with traditional pretreatment and treatment-related variables and will improve our ability to predict outcome and select the optimal treatment. Cancer 2009;115(13 suppl):3112-20. (c) 2009 American Cancer Society.

Figure 1

Figures 1a and 1b Two examples of outcomes predicted by Kattan nomogram for men with clinically localized prostate cancer treated with three-dimensional conformal external beam radiotherapy . In the first example (Figure 1a), a patient with a PSA of 4 ng/ml, clinical stage T3c disease, a Gleason Score of 10, and is treated to 72 Gy with short-term androgen deprivation therapy. The nomogram predicts a five-year control rate of 70%. Such patients usually do very poorly and can be expected to have a very high relapse rate. In the second example (Figure 1b) a patient is has a low T-stage, Gleason Score, dose of radiation and no hormonal therapy but a high PSA (25 ng/ml) is predicted to have a worse outcome. His survival would be expected to be higher than the patient in the first example however.

Figure 1

Figures 1a and 1b Two examples of outcomes predicted by Kattan nomogram for men with clinically localized prostate cancer treated with three-dimensional conformal external beam radiotherapy . In the first example (Figure 1a), a patient with a PSA of 4 ng/ml, clinical stage T3c disease, a Gleason Score of 10, and is treated to 72 Gy with short-term androgen deprivation therapy. The nomogram predicts a five-year control rate of 70%. Such patients usually do very poorly and can be expected to have a very high relapse rate. In the second example (Figure 1b) a patient is has a low T-stage, Gleason Score, dose of radiation and no hormonal therapy but a high PSA (25 ng/ml) is predicted to have a worse outcome. His survival would be expected to be higher than the patient in the first example however.

Figure 2

Example of use of Kattan nomogram for predicting risk of metastasis at 5 years following three-dimensional conformal radiotherapy , . This nomogram was subsequently validated as predictive of cause specific and overall survival in patients treated at UCSF and University of Michigan as shown in Figure 4 , .

Figure 3

Disease Specific Survival (DSS) is shown by RTOG Risk Group. Analysis is based on 1500 patients treated with external beam radiotherapy alone on RTOG 8531 and 8610. From top to bottom, Risk Group 1 defined as: Stages T1-2, Nx, Gleason 2–6; Risk Group 2 defined as: Stages Gleason 2–6 and T3Nx or N+ or Gleason score=7, T1-2 Nx; Risk Group 3 defined as: T3Nx with Gleason Score=7 or N+ and Gleason score=7 or Stages T1-2, Nx, Gleason 8; Risk Group 4 defined as: T3Nx with Gleason Score=8–10 or N+ Gleason score=8–10.

Figure 4

Disease Specific Survival (DSS) is shown by estimated risk of distant metastases using the Kattan Nomogram , . Note highly significant differences are observed in DSS among the 3 tertiles created by the nomogram (cut-points: <8.5%, 8.5% – 15%, and > 15%) (p < 0.001).