The RTOG 94-08 clinical trial was designed to test the idea that just 4 months of hormone therapy, administered before and during radiation therapy, would improved the overall survival of patients diagnosed with clinical stage T1b-T2b prostate cancer and a PSA level equal to or lower than 20 ng/ml.
The final results of this trial were presented yesterday by McGowan et al. at the Genitourinary Cancers Symposium in San Francisco.
Starting back in October 1994, patients who met the above criteria were randomized to treatment with external beam radiation therapy alone (EBRT) or to 4 months of “total androgen deprivation therapy (i.e., and LHRH agonist + an antiandrogen) starting 2 months prior to EBRT. The form of the EBRT was identical in both arms.
The results of this trial can be summarized as follows:
- 1,979 eligible patients were randomized to receive EBRT alone (n = 992) or EBRT + ADT (n = 987).
- The median age of the patients was 71 years.
- 964/1,979 patients (49% percent had T1 tumors and 1,015/1,979 patients (51 percent) had T2 tumors.
- 209/1,979 patients (11 percent) had a PSA level < 4 ng/ml and 1,770/1,979 patients (89 percent) had a PSA level between 4 and 20 ng/ml.
- Gleason scores were between 2 and 6 in 1,215/1,979 patients (61 percent), 7 in 538/1,979 patients (27 percent), between 8 and 10 in 180 patients (9 percent), and unknown in 46/1,979 patients (2 percent).
- 1,501 patients (76 percent) were white, 395 (20 percent) were black, and 83 (4 percent) were of other race.
- The median follow up time of all eligible patients was 8.4 years in the EBRT + ADT arm and 8.1 years in the EBRT onlyarm.
- Estimated overall survival at 12 years was 51 percent in the EBRT +ADT arm and 46 percent in the EBRT only arm, and this difference was statistically significant (p = 0.03).
- Rebiopsies were carried out with the following outcomes:
- 439/987 patients in the EBRT + ADT arm were rebiopsied, and 105/439 patients (22 percent) were rebiopsy positive.
- 404/992 patients in the EBRT only arm were rebiopsied, and 159/404 patients (40%) were rebiopsy positive.
- Acute and late radiation toxicity was similar in both arms.
- Hormonal toxicity was mainly observed to the liver and was Grade 3 or Grade 4 in < 5 percent of patients.
- Hormonal cardiovascular toxicity was grade 1 or 2 in 13 patients (1 percent).
The authors conclude that the addition of 4 months of “total” ADT given prior to and during EBRT significantly improved overall survival in patients with T1b-T2b cancer of the prostate and with a PSA ≤ 20 ng/ml. Tehy also stated that analysis of secondary endpoints and risk-stratified subsets continues to help identify those patients who benefit most from androgen suppression.
This trial was initiated over 15 years ago, and we have vastly improved the technical ability to appropriately direct radiation to the prostate since that time. We would expect to see a much lower rate of positive rebiopsies if this trial was redone, starting today, and using high dose IMRT or IGRT instead of the type of radiation therapy applied in the early to mid 1990s. However, it is also clear from this study that at least a subset of patients with localized disease who elect radiation therapy will benefit from short-term hormone therapy in association with the radiation. It is also likely that these are the patients at higher levels of risk for progressive disease (intermediate- and high-risk using the D’Amico criteria).
It will be interesting to see exactly how much guidance the RTOG 94-08 resreach team can pull out of their database to guide us about which patients are likley to benefit most from short-term, neoadjuvant hormone therapy in conjunction with radiation for localized disease.