Prostate Cancer: Likelihood of Death from Intermediate Risk Disease Interview with:
Florence K. Keane, MD
Harvard Radiation Oncology Program, Harvard Medical School
and Anthony V. D’Amico, MD, PhD
Department of Radiation Oncology,
Dana Farber Cancer Institute and Brigham and Women’s Hospital, Boston, Massachusetts What are the main findings of the study:

Answer: Patients with unfavorable intermediate-risk prostate cancer (PC) [1] have an increased risk of PC-specific mortality (PCSM) after radiotherapy (RT) with or without androgen suppression therapy (AST) compared to favorable intermediate-risk patients [2,3]. We provided validation for this prognostic subdivision using mature data with a median follow-up of 14.3 years from a prospective randomized trial comparing RT alone with RT and 6 months of AST [4].  We also assessed the risk of PCSM in patients with unfavorable intermediate-risk PC compared with high-risk prostate cancer.

Our main findings were as follows.

  • First, there were no prostate cancer deaths observed in favorable intermediate-risk patients, despite 50% receiving RT alone.
  • Second, there was not a statistically significant difference in the risk of PCSM in men with unfavorable intermediate-risk prostate cancer compared to men with high-risk PC after randomizing for age, comorbidities and treatment arm. While it is possible that a difference may emerge with longer follow-up, these results suggest that some men with unfavorable intermediate-risk PC may harbor occult GS 8-10 disease and could benefit from a 3.0-Tesla multiparametric MRI and targeted biopsy to rule out GS 8-10 disease. Were any of the findings unexpected?

Answer: The lack of prostate cancer deaths in favorable intermediate-risk patients, despite 50% receiving RT alone, was intriguing and suggests that AST may not be needed to improve outcomes in this population.  It is important to note that the favorable intermediate-risk patients in our study were a healthy population with clinically significant cancers who would not have been appropriate candidates for active surveillance, as 43% had GS 3+4, 30% had T2a lesions, and 86% had no or minimal comorbidities. What should clinicians and patients take away from your report?

Answer: First, as noted above, physicians treating men with unfavorable intermediate-risk prostate cancer may wish to consider a 3.0-Tesla multiparametric MRI with diffusion weighted imaging and targeted biopsy of suspicious areas to rule out occult GS 8-10 disease. Patients who are found to have GS 8-10 disease should receive treatment for high-risk PC with 28 to 36 months of AST instead of the 4 to 6 months of AST currently used in intermediate-risk PC.

Second, the lack of benefit with androgen suppression therapy in favorable-intermediate risk patients in our study is especially important given the potential toxicities associated with AST [5,6]. Monotherapy with dose-escalated RT or radical prostatectomy may be appropriate for favorable intermediate-risk patients. What recommendations do you have for future research as a result of this study?

Answer: There are several opportunities for further research on the risk of PCSM in favorable and unfavorable intermediate-risk PC.   The currently accruing RTOG 0815 [7], a phase 3 trial of intermediate-risk patients randomized to dose-escalated RT with or without 6 months AST will provide information on the role of short term AST in men with favorable or  unfavorable intermediate-risk PC. However, it will not answer whether long-term AST would improve outcomes in men with unfavorable intermediate-risk PC.

It will be important for future trials to consider the proportion of subjects with favorable or unfavorable intermediate-risk PC, as this balance may impact outcomes.  For example, there was no significant difference in estimates of PCSM in RTOG 9910 [8], a trial of predominantly intermediate-risk PC patients (84%) randomized to 8 weeks versus 28 weeks of neoadjuvant AST prior to 8 weeks of concurrent AST and RT.  Complete data on the proportion of patients with favorable intermediate-risk PC is not yet available, but enrollment of a significant number of favorable intermediate-risk patients would have decreased the power of the study to observe a difference in PCSM. RTOG 9910’s 10 year estimated PCSM of 4-5%, which is lower than the 7.8% 10 year estimated PCSM in unfavorable intermediate-risk PC in our study suggests that some patients had favorable intermediate-risk prostate cancer. Therefore, the role of long-term AST in unfavorable intermediate-risk PC is not yet known.


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The likelihood of death from prostate cancer in men with favorable or unfavorable intermediate-risk disease

Keane, F. K., Chen, M.-H., Zhang, D., Loffredo, M. J., Kantoff, P. W., Renshaw, A. A. and D’Amico, A. V. (2014), The likelihood of death from prostate cancer in men with favorable or unfavorable intermediate-risk disease. Cancer. doi: 10.1002/cncr.28609