Chemo+ADT+RT: No benefit after ten years

Earlier this month, we looked at the evidence of benefit for adding chemo to radiation therapy for high-risk prostate cancer (see “Docetaxel with radiation in prostate cancer treatment”). Early results of RTOG 0521 showed only a modest benefit in the short term. Would longer term follow up reveal a greater benefit?

We now have a ten-year update of RTOG 9902, a clinical trial begun in 2000 and closed to accrual in 2004 because of excess toxicity. Although the study ended before it met its accrual goal, patients continued to be tracked. The study protocol included:

• ·      380 high-risk patients were randomized to two arms
• ·      High Risk:

o   Gleason score≥7 and PSA from 20 to 100 ng/ml or

o   Gleason score≥8 and stage≥T2

• ·      Two arms:

o   Chemo + ADT + RT

o   ADT + RT

• ·      Chemo: Paclitaxel + Estramustine + Etoposide
• ·      ADT: LHRH agonist (24 months) + anti-androgen (4 months), both begun 2 months before RT
• ·      RT: 70 Gy

The ten-year results were as follows:

• ·      Overall survival: 63% with chemo, 65% without chemo (no sig. difference)
• ·      Local progression: 7% with chemo, 11% without chemo (no sig. difference)
• ·      Distant metastases: 14% with chemo, 16% without chemo (no sig. difference)
• ·      Disease-free survival: 26% with chemo, 22% without chemo (no sig. difference)

Before we write off adjuvant chemo with radiation entirely, we must acknowledge that the clinical trial was begun before docetaxel became available. Docetaxel is far more effective and far less toxic than the chemo used in this study. They also used a radiation dose of only 70 Gy, which we now know to be inadequate for high-risk patients. So far, all we can conclude is that we don’t have enough evidence to change the standard of care to include chemo with radiation.