10-year outcomes after high-dose IMRT for localized prostate cancer

A new report from Memorial Sloan-Kettering Cancer Center has documented patient outcomes at 10 years after high-dose, intensity-modulated radiation therapy (IMRT)  for men initially diagnosed with clinically localized prostate cancer. This is believed to be the first report of 10-year outcomes after high-dose IMRT.

Alicikus et al. have published data from a series of 170 patients, all of whom were treated with 81 Gy between April 1996 and January 1998 using 5-field IMRT. Patients were carefully categorized by risk group, using risk group definitions specified by the National Comprehensive Cancer Network (NCCN). 

The key results reported by Alicikus et al. are as follows:

  • Median follow-up was 99 months.
  • Actuarial biochemical progression-free survival rates at 10 years were
    • 81 percent for low-risk patients
    • 78 percent for intermediate-risk patients
    • 62 percent for high-risk patients
  • Actuarial distant metastasis-free survival rates at 10 years were 
    • 100 percent for low-risk patients
    • 94 percent for intermediate-risk patients
    • 90 percent for high-risk patients
  • Prostate cancer-specific mortality rates at 10 years were 
    • 0 percent for low-risk patients
    • 3 percent for intermediate-risk patients
    • 14 percent for high-risk patients
  • The probabilities of development of  grade 2 and grade 3 late genitourinary toxicity at 10 years were 11 and 5 percent, respectively.
  • The probabilities of development of  grade 2 and grade 3 late gastrointestinal toxicity were 2 and 1 percent, respectively.
  • No grade 4 toxicities were observed.

Based on these data, it appears that high-dose IMRT is well tolerated and offers a high level of tumor-control for men with localized prostate cancer. However, these data reflect a case series from a major academic prostate cancer center, and they are not compared to data from other patients treated using lower doses of IMRT or high doses of radiation using other forms of radiation. The abstract of the study makes no mention of data on erectile function over time.

2 Responses

  1. These are impressive results for IMRT!

    Some of us first heard about the promise of EBRT with higher doses at the National Conference on Prostate Cancer 2000 in Long Beach, CA. We heard Dr. Patrick Kupelian from the Cleveland Clinic talk with excitement and passion about improved results of higher dose external beam radiation (EBRT), but back then the higher doses that were more successful were 72 Gy or higher, considerably less, overall, than the 81 Gy covered in this research.

    However, I’m not as enthusiastic about the 81 Gy results as I’m following up on Sitemaster’s point about results from other forms of high-dose radiation. I’m looking at an informally published set of risk-group tables from the Prostate Cancer Results Study Group (PCRSG) that displays progression-free survival versus time since treatment as documented in various studies.

    For low-risk patients, the PCRSG table shows 11 brachytherapy results in the 9.5 to 12 years-since-treatment timeframe that are substantially superior overall to the 81 Gy result, with none of the brachytherapy results less than about 3 percentage points better than the 81 Gy result. The only other EBRT result with similar maturity for low-risk patients shows similar success of about 82% at about the 9.5 year point. Two EBRT/seed combo results for low-risk patients with similar maturity were also better by about 10 percentage points than the 81 Gy results.

    For intermediate-risk patients with a similar maturity of time since treatment, there are nine radiation studies displayed, with three brachytherapy studies showing results averaging a few percentage points better and one showing about the same success … but with what looks like another year and a half more time since treatment. Five studies with similar or longer follow-up involving EBRT/seed combos are all at least somewhat superior to the 81 Gy results, with two of those studies logging average or actuarial average follow-up of about 14 to 15 years.

    For high-risk patients, there is only one brachytherapy study with similar followup, and the result is almost identical to the result of 62% success for the 81 Gy patients. However, for research with similar or longer follow-up, there are 13 studies involving combos of EBRT + seeds (10 studies), EBRT + seeds + hormonal therapy (one study), or just EBRT (two studies). The 81 Gy results are superior to the two other EBRT-only studies. The 81 Gy results are about equal to two of the EBRT + seeds studies and superior to three others. The 81 Gy results are distinctly less successful than five EBRT + seed combo studies and one EBRT + seeds + ADT study.

    It’s probably hard to visualize the foregoing without viewing the tables, but with the tables before me I’m thinking that 81 Gy IMRT alone, while good, is just not as good as good as brachytherapy or brachy/IMRT (depending on the risk level) from the viewpoint of progression-free survival.

    I also picked up on Sitemaster’s hint about higher doses of IMRT and found another recent report from Memorial Sloan-Kettering, again involving Dr. Zelefsky (Deutsch et al. 2010). This study used an “ultra-high” IMRT dose of 86.4 Gy, with these 5-year actuarial PSA relapse-free survival results for low-, intermediate-, and high-risk patients: 98%, 84%, and 71%. That low-risk result of 98% for 86.4 Gy is obviously competitive at the 5-year mark with all comers, but there are numerous studies for brachytherapy and brachy/EBRT combos that do better for intermediate-risk patients (and some not as well). For high-risk patients, while the 71% for the 86.4 Gy is distinctly superior to the other EBRT studies at the 5-year point, that 71% success just doesn’t look competitive to me with the majority of brachytherapy/EBRT, or brachytherapy/EBRT plus hormonal blockade combos.

    As the dust settles, I’m thinking that the higher doses of IMRT at a center of excellence may be superior choices if brachytherapy or a brachytherapy/IMRT combo, perhaps with hormonal therapy as an adjuvant, are not appropriate for the patient. The PCRSG data did also cover some high dose rate (HD) brachytherapy studies, which I haven’t addressed. Of course stereotactic body radiotherapy (SBRT) is also now calling for attention (but with very short documented follow-up.) Proton research is scant, and, while looking equal to or superior to some of the older EBRT results, did not look competitive with the Memorial Sloan-Kettering 81 Gy and 86.4 Gy research, nor with numerous brachytherapy and brachytherapy/IMRT (perhaps with hormonal therapy) combos, nor with HDRe brachytherapy.

  2. I’m following-up regarding the high dose rate (HDR) brachytherapy studies in the PCRSG tables, an area not covered in the earlier reply.

    There were no HDR studies displayed for low-risk patients. I don’t know if there just have been no HDR studies for that group, which would be odd, or if there have been no studies that met the PCRSG criteria (numbers of patients, length of follow-up, etc.).

    For intermediate-risk patients, there were five HDR studies, all with average follow-up of about 5 years since treatment, and all with success above 85%: one in the upper 90s, one in the low 90s, and three in the upper 80s. These rates are all better than the 78% for 81 Gy, but that 81 Gy result is based on approximately double the follow-up time.

    There were six HDR studies involving high-risk patients. Results for two at around the 5-year point ranged from the high at about 79% to the low at about 50%. One medium-term follow-up result was approximately 70% at about 7 years of follow-up. Three longer follow-up HDR studies included one at approximately 70% at 8.5 years, one at approximately 62% at about 9e years, and one at about 63% at about 10 years. These latter two results are highly similar to the success rate of 62% for 81 Gy IMRT at the 10-year point, as reported above.

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