When is “immediate” adjuvant radiation therapy most appropriate after RP?

The appropriate use of “immediate” adjuvant radiation therapy after a man has a radical prostatectomy (RP) has long been controversial. Although a small number of clinical trials have attempted to address the relative benefits of adjuvant radiation as compared to salvage radiation (with and without additional androgen deprivation), there is still no real consensus.

A recent study by an Italian research team has suggested that the greatest impact of “immediate” adjuvant radiation therapy on overall mortality (OM) and on prostate cancer-specific mortality (PCSM) may be limited to a well-defined subset of patients … but these data certainly need to be confirmed by others before we take them as some sort of gospel truth.

Abdollah et al. carried out a retrospective analysis of data from a series of men who had received an RP for localized or locally advanced prostate cancer. As part of their RP, all the men also received an extended lymph node dissection. The patients may then have received a variety of immediate or delayed treatments in the 10-year period from 1998 to 2008. To be eligible for inclusion in the study analysis, the men had to have

  • Positive surgical margins and/or
  • pT3 or pT4 disease

The primary goal of the study was investigate whether immediate adjuvant radiation therapy (ART) affected either the PCSM or the OM rates of men with a series of well-defined pathologic features, including positive surgical margins, extracapsular extension, seminal vesicle invasion, pathologic stage T4 tumor, and/or pathologically positive lymph nodes.

Here are the core findings of the study.

  • A total of 1,049 patients met eligibility criteria for inclusion in the analysis.
  • On multivariable analyses, only three pathologic features represented independent predictors of PCSM:
    • A pathologic Gleason score ≥ 8 (hazard ratio [HR] = 5.4; p ≤ 0.02)
    • The presence of pT3b or pT4 disease (HR = 2.2; p ≤ 0.02)
    • The presence of one or more positive lymph nodes (HR = 2.6; p ≤ 0.02)
  • The total number of these factors shared by each patient was used to develop a new type of risk score, ranging from 0 to 3:
    • 43.6 percent of patients had a risk score of 0.
    • 22.1 percent of patients had a risk score of 1.
    • 20.7 percent of patients had a risk score of 2.
    • 13.6 percent of patients had a risk score of 3.
  • Among men with a risk score of 2 or 3:
    • Those treated with ART had a 10-year PCSM rate of 20.1 percent.
    • Those not treated with ART had a 10-year PCSM rate of 30.4 percent.
    • Those treated with ART had a 10-year OM rate of 24.4 percent.
    • Those not treated with ART had an OM rate of 37.3 percent.
  • Among men with a risk score of 0 or 1:
    • Those treated with ART had a 10-year PCSM rate of 2.4 percent.
    • Those not treated with ART had a 10-year PCSM rate of 3.4 percent.
    • Those treated with ART had a 10-year OM rate of 5.0 percent.
    • Those not treated with ART had an OM rate of 11.5 percent.

The authors are careful to point out that, “The observational nature of the cohort represents a limitation of the study.” However, it does appear clear that, for this series of patients, rates of PCSM were not significantly affected by the application of immediate adjuvant radiation therapy in patients with only one or none of the pathologic criteria defined above. However, there does appear to have been a small affect on the OM rate even in men with one or none of these pathologic criteria. (It is not clear from the available data whether this latter effect is statistically significant.)

Abdollah et al. conclude that patients with at least two of the defined pathologic criteria “represent the ideal candidates for ART after RP.” Note that they do not state that ART is necessarily inappropriate for other carefully selected patients.

It would be helpful to see a similar analysis of data from another large series of patients for whom the same range of data were available. It would also be helpful to know whether the extent of positive margins had any similar effect, since it does not appear that Abdollah et al. subcategorized their patients into those with “limited” or “extensive” positive margins (although that can be challenging).

The “New” Prostate Cancer InfoLink would agree with Abdollah et al. that these data do indeed help us to define the “ideal candidates for ART after RP.” However, as noted earlier, confirmation of these results would add further confidence to this recommendation.

4 Responses

  1. If I understand this correctly, My Gleason 7, pT3bN0Mx is indicative of a risk score of 1. And I could possibly have benefited by my election to go with ART?

  2. Tony:

    Since I haven’t seen the full text of the paper by Abdollah et al., I have no idea how many of the men in their study were under 50 years of age at the time of treatment.

    As I noted above, just because one doesn’t meet their criteria for being an “ideal” patient for ART also doesn’t mean that ART may not be appropriate. Age at the time of treatment may be a factor. The authors do not appear to have subcategorized their patients by age group, but I can’t be sure.

  3. Would radiation therapy alone for PSA < 0.1 at 6-12 months following RP (without ADT) with pT3aN1 be considered salvage or ART?

  4. If the patient’s PSA fell to < 0.1 and was stable after surgery, then this would be considered to be adjuvant radiation therapy since salvage radiation therapy normally implies a PSA that either never went to < 0.1 ng/ml or is rising after reaching a nadir level. However, if the PSA was rising but still below 0.1 ng/ml (as measured with ultrasensitive PSA tests, e.g., rising from 0.005 to 0.08 ng/ml over months 3-9 post-surgery), it could reasonably be classified as salvage radiation.

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