Chemo + ADT + RT: no benefit after 10 years


Earlier this month, we looked at the evidence of benefit for adding chemotherapy to androgen deprivation therapy (ADT) + radiation therapy (RT) 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 10-year update of data from 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, randomized to two treatment arms
  • “High risk” patients were
    • Either Gleason score ≥ 7 and PSA between 20 and 100 ng/m
    • Or Gleason score ≥ 8 and clinical stage ≥ T2
  • The two treatment arms were:
    • Either chemotherapy + ADT + RT
    • Or ADT + RT
    • In which
      • Chemotherapy was: paclitaxel + estramustine + etoposide
      • ADT was: an LHRH agonist (for 24 months) + an antiandrogen (for 4 months), both begun 2 months before RT
      • The dose of RT was: 70 Gy

The 10-year results were as follows:

  • Overall survival: 63 percent among men receiving chemotherapy; 65 percent among those without chemotherapy (no significant difference)
  • Local progression: 7 percent among men with chemotherapy; 11 percent among those without chemotherapy (no significant difference)
  • Distant metastases were seen in: 14 percent of men receiving chemotherapy; 16 percent among those without chemotherapy (no significant difference)
  • Disease-free survival: 26 percent among men receiving receiving chemotherapy; 22 percent among those without chemotherapy (no significant difference)

Before we write off adjuvant chemotherapy with radiation entirely, we must acknowledge that this clinical trial was begun before docetaxel (Taxotere) was shown to be active in the treatment of advanced prostate cancer. Docetaxel is far more effective and far less toxic than the chemotherapy used in this study. The study 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 chemotherapy with radiation + ADT.

Editorial note: This commentary was written for The “New” Prostate Cancer InfoLink by Allen Edel.

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