Outcomes of HDR brachytherapy + IMRT vs. very high-dose IMRT alone

As far as we are aware there are limited data comparing the outcomes of patients treated with high-dose IMRT to those of patients treated with high-dose-rate (HDR) brachytherapy + IMRT as first-line therapy.

Zelefsky et al. have published a retrospective analysis of biochemical outcomes at a single academic center after very high doses of conventionally fractionated intensity-modulated radiation therapy (IMRT) compared to high-dose-rate (HDR) brachytherapy combined with lower doses of IMRT in a total of 630 patients.

Patients were categorized into one of two groups:

  • Patients in Group A (n = 470) received conventionally fractionated IMRT at a total dose of 86.4 Gy.
  • Patients in Group B (n = 160) received HDR brachytherapy (21 Gy in three fractions) followed by IMRT of 50.4 Gy.

In adeditiona, patients were categorized as low-, intermediate-, or high-risk uring the National Comprehensive Cancer Network (NCCN) risk criteria. Biochemical relapse after treatment was defined according to the Phoenix criteria (a PSA level that exceeded the PSA nadir + 2 ng/ml). Median follow-up was 53 months for IMRT alone and 47 months for HDR + IMRT.

The results reported by Zelefsky and his colleagues are as follows:

  • The 5-year actuarial biochemical progression-free survival (bPFS) for HDR + IMRT vs. high-dose IMRT, classified by risk group were
    • 100 vs. 98 percent for low-risk patients
    • 98 vs. 84 percent for intermediate-risk patients (which was statistically significant)
    • 93 vs. 71 percent for high-risk patients
  • Treatment, clinical T stage, Gleason score, pretreatment PSA level, risk group, and lack of androgen deprivation therapy (ADT) were all significantly associated with improved bPFS on univariate analysis.
  • HDR + IMRT vs. ultra-high-dose IMRT, patient age, and risk group were significantly associated with improved bPFS on multivariate analysis.
  • The abstract provides no data on the comparative adverse effects of the two types of radiation therapy.

The authors conclude that dose escalation carried out by adding IMRT to HDR brachytherapy provided improved bPFS in the treatment of prostate cancer compared with very high-dose IMRT, independent of risk group on multivariate analysis. The most significant benefit appeared to be available for intermediate-risk patients.

Since this was not a randomized trial, and the information available in the abstract of the paper is limited, one must be cautious about how to interpret these data. It is not, for example, clear how long ago these patients were treated. Nor is it clear what their clinical stages were at the time of therapy. Nor do we know how many of the patients received neoadjuvant and/or adjuvant ADT. Access to the entire paper might answer some of these questions, but perhaps not all of them.

The other relevant issue here is the degree of significance of the biochemical progression. It is becoming increasingly evident that many patients who have biochemical progression never have clinically significant progression after their PSA level meets current criteria for biochemical progression. What percentage of these patients are then getting second-line therapy that has very limited merit?

3 Responses

  1. Interesting about the negative correlation between ADT and bPFS. Many radiation centers recommend ADT for Gleason 7 and up.

  2. One wonders why these papers get published since no conclusions can be made.

  3. Well, I suppose those whose interests are more in the field of health economics than medicine may find these data to be useful, and it is possible that the full paper gives additional data that might be helpful — but publishers are also interested in publishing information that causes discussion. The costs of widely used forms of treatment are likely to cause discussion, I think, at least today.

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