Friday, November 14, 2014

Radiation Therapy after Prostate Surgery, Part II: Subgroups Who May Benefit From Adjuvant Therapy

Some men prostate cancer are faced with the realization that treatment of their prostate cancer may require multimodal treatment including some combination of surgery, radiation therapy and/or hormone therapy. The combined ASTRO/AUA (American Society for Therapeutic Radiology and Oncology/American Urological Association) Guideline for "Adjuvant and Salvage Radiotherapy after Radical Prostatectomy" makes a number of statements regarding the use of radiation therapy after surgery that can be confusing to patients and practitioners. 

In the second part of this blog series, we review the statements from the ASTRO/AUA Guideline regarding subgroups who may benefit from adjuvant radiation therapy and the data supporting them.

To read Part I: Adjuvant Radiation following Surgery for Prostate Cancer click here.

The Guideline Statements and three randomized studies (SWOG 8794, EORTC 22911, and ARO 96-02/AUO 09/95) that support their conclusions are detailed in Part I. To summarize, Part I:
Adjuvant radiation therapy (ART) is an option for men with advanced prostate cancer and adverse features after radical prostatectomy. Patients who undergo ART can expect an improvement in biochemical (PSA) and locoregional recurrence, although the benefits on distant metastases and overall survival is less clear.

Looking closely at the data regarding ART, some patients – or subgroups – may be more likely to benefit from immediate treatment than others. It is important to mention before delving into the data from these studies, that these trials were not designed to investigate sub-groups and conclusions need to be drawn with care.

For instance, the SWOG trial demonstrated a benefit for all patients receiving ART. However, when looking at subgroups, patients with high Gleason score (7-10) had the largest significant effect.

From Thompson et al. Journal of Urology, 2009.
In the ARO/AUO trial, benefit was seen for patients with positive surgical margins, high PSA, extraprostatic extension only and all Gleason scores – rather confusing.

From Wiegel et al. JCO 2009; 27: 2898.
To gain a better perspective, we will analyze each adverse feature individually.



For patients without a positive surgical margin, there was no benefit to ART for biochemical recurrence, metastasis-free survival (MFS) or overall survival (OS) in the EORTC or ARO studies (SWOG did not report data for patients without positive margins).
For patients with a positive surgical margin, all three studies demonstrated a benefit to ART with regard to biochemical recurrence. SWOG and the EORTC study demonstrated improved recurrence-free survival (or MFS) – ARO did not report this data. OS was not improved in the EORTC study – the only trial that demonstrated this data.



For patients with Gleason Score 2-6:

  • Both the EORTC and ARO study demonstrated an improvement in biochemical recurrence.
  • SWOG did not show a benefit in MFS.
For patients with Gleason Score 7-10:
  • ARO demonstated a benefit to biochemical-free survival
  • SWOG demonstrated an improvement in MFS
  • EORTC did not demonstrate a benefit in biochemical recurrence for either patients with Gleason 7 or patients with Gleason 8-10.
    • The effect for patients with Gleason 7 was apparent, but not statistically significant (Hazard Ratio: 0.63, 95% Confidence Interval: 0.38-1.0).



For patients with extraprostatic extension (pT3a),
  • EORTC and ARO demonstrated a benefit with regard to biochemical recurrence.
  • EORTC did not demonstrate a benefit for recurrence-free survival or OS.
  • SWOG did not report on patients with extraprostatic extension.



For patients with seminal vesicle invasion (pT3b),
  • SWOG and EORTC demonstrated a benefit with regard to biochemical recurrence, ARO did not.
  • Neither SWOG nor EORTC demonstrated a benefit to recurrence-free survival or MFS.
  • EORTC did not demonstrate an OS benefit to ART.


Based on the subgroup analyses, adjuvant ART appears to have the most benefit for patients with positive surgical margins and Gleason score 7-10. The benefit of ART in patients with Gleason 6, extraprostatic extension (in the absence of a positive surgical margin) and seminal vesicle invasion is less clear.

This is most likely explained by the fact that patients with a high Gleason score and positive surgical margin are at risk for residual, local disease and benefit from additional local therapy (in the form of radiation). Patients with Gleason 6 are unlikely to benefit as Gleason 6 is believed to be indolent disease and extra therapy to the pelvis is unlikely to affect an already slow-growing, benign-behaving disease process. Patients with seminal vesicle invasion have the opposite problem – they are at extremely high-risk for systemic disease, or disease that has spread from the prostate. Therefore, treating the pelvis is unlikely to benefit patients who are likely to have disease in their lymph nodes or bones – and catching the prostate cancer in the pelvis with additional radiation therapy is unlikely.
Stay tuned for this continued series on Radiation Therapy after Surgery for Prostate Cancer.


This blog was written by Mark W. Ball, MD. Mark is a 5th year urology resident at the Brady Urological Institute at Johns Hopkins and looking forward to a career in urologic oncology.


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