Results of RTOG 94-08 finally published in NEJM

As we first reported in March 2010, when data were originally presented at the Genitourinary Cancers Symposium, RTOG 94-08 has shown that 4 months of androgen deprivation therapy (ADT) before and during external beam radiation therapy (EBRT) reduces the overall and the prostate cancer-specific mortality rates for men with localized prostate cancer (clinical stages T1b, T1c, T2a, or T2b).

The final data from this trial have now been published by Jones et al., and a related media release has been issued by the National Cancer Institute (NCI).

The results of this trial, as now reported in the New England Journal of Medicine, are as follows:

  • The average (median) follow-up for 1,979 patients was 9.1 years.
  • The 10-year overall survival rates of the patients in the two arms of the study were
    • 62 percent for the 987 patients receiving radiotherapy plus short-term ADT (the combined therapy group)
    • 57 percent for the 992 patients receiving radiotherapy alone
  • The hazard ratio (HR) for death with radiotherapy alone was 1.17 (P = 0.03).
  • The addition of short-term ADT to EBRT was associated with a decrease in the 10-year disease-specific mortality from 8 to 4 percent (HR for radiotherapy alone, =1.87; P = 0.001).
  • Rates of biochemical failure, distant metastases, and positive findings on repeat prostate biopsy at 2 years were all significantly improved with radiotherapy + short-term ADT as compared to ADT alone.
  • Acute and late radiation-induced toxic effects were similar in the two groups.
  • The incidence of ADT-related toxic effects of grade 3 and higher was less than 5 percent.
  • Reanalysis according to risk showed that
    • Reductions in overall and disease-specific mortality occurred primarily among intermediate-risk patients.
    • There were no significant reductions in overall and disease-specific mortality among low-risk patients.

The bottom line to this study now appears to be that 4 months of neoadjuvant and adjuvant ADT in combination with EBRT can improve the 10-year overall and prostate cancer-specific mortality rates among men with intermediate-risk, localized prostate cancer (clinical stages T1b, T1c, T2a, or T2b) compared to EBRT alone, but has no significant added benefit in men with low-risk, localized disease. According to the media release issued by the NCI, these outcomes were similar among Caucasian and African-American cohorts of patients enrolled in this study.

The degree to which the results of this study really make a major difference to the first-line treatment of localized prostate cancer is open to some degree of question. This study was initiated more than 15 years ago, when the best form of external beam radiation therapy was three-dimensional, conformal radiation therapy (3D-CRT) and before the adoption of even the earliest types of intensity-modulated radiation therapy (IMRT), let alone some of the more sophisticated evolutions of modern radiation therapy for prostate cancer. Arguably, however, 4 months of ADT — starting 2 months prior to the actual radiation — would have few long-term side effects for the vast majority of patient, and might significantly improve the long-term survival of those with intermediate-risk disease.

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