Exceptions to “early salvage” radiation treatment for recurrence after prostatectomy

Three major randomized clinical trials and a meta-analysis have proved that for most men waiting for early signs of recurrence after prostatectomy (e.g., three consecutive PSA rises or a PSA of 0.1 ng/ml) to give radiation gave the same outcome as immediate (“adjuvant”) radiation (see this link). But there are exceptions. In some men, adjuvant treatment is better. In some men, early salvage may overtreat them.

Adjuvant Radiation Therapy

Tilki et al. carried out a retrospective study of 26,118 men given prostatectomies at several hospitals in Germany, UCSF, and Johns Hopkins. Of those 26,000+ patients, 2,424 of them had “adverse pathology” defined as:

  • Positive lymph nodes, or
  • A Gleason score of 8-10, and
  • Pathological stage T3 or T4

Patients were treated with adjuvant radiation therapy (ART) within 6 months of prostatectomy; or salvage radiation therapy (SRT) after their PSA rose above 0.2 ng/ml (i.e., biochemically recurrent disease or BCR); or no radiation therapy (no RT). They matched patients on age, initial PSA, and positive/negative margin status.

For men with adverse pathology, including positive lymph nodes, 10-year all-cause mortality was:

  • 14 percent for ART
  • 27 percent for no RT
  • 28 percent for SRT

For men with adverse pathology, but without positive lymph nodes, 10-year all-cause mortality was:

  • 5 percent for ART
  • 25 percent for no RT
  • 22 percent for SRT

For men with no adverse pathology, 10-year all-cause mortality was:

  • 8 percent for ART
  • 9 percent for no RT
  • 8 percent for SRT

This suggests that for men with adverse pathology, ART improves outcomes over early SRT.

No/delayed SRT

At the other end of the risk spectrum are men with such low risk for clinical recurrence, that salvage radiation can be delayed, perhaps indefinitely. This is based on the observation that while 40 percent of post-prostatectomy patients may experience a BCR, only 30 percent of BCR patients develop a clinically relevant recurrence, and all but 16 percent die of something else before the recurrent cancer kills them.

In a major review for the European Urological Association (EAU), Van den Broeck et al. reviewed 77 studies covering 20,406 patients who were biochemically recurrent (conventionally measurable PSA) after prostatectomy. They sought to define the patient and disease characteristics that determined which of the BCR cancers led to distant metastases and death from prostate cancer. They found that the following risk characteristics defined a “low risk” BCR prostate cancer that could be safely watched:

  • PSA doubling time > 1 year
  • Gleason score < 8
  • Interval to biochemical failure > 18 months

Tilki et al. validated the EAU study in a retrospective study of 1,125 patients. Preisser et al. validated the study retrospectively among 2,473 men. Pompe et al. validated the risk group in a retrospective study of 1,821 men. To date, there has been no prospective validation in a randomized clinical trial. Zaorsky et al. point out some additional characteristics of recurrent patients who may be safely watched:

  • PSA < 0.5 ng/ml at time of recurrence
  • Age > 80 years of age
  • Significant comorbidities, competing causes of death
  • No distant metastases detected with PET/CT imaging (Ferdinandus et al.)

It is undoubtedly better to have a low Decipher score as well.

Lacking prospective validation, this is a decision that should be carefully discussed between the patient and the radiation oncologist.

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

2 Responses

  1. It is not clear how many of Zaorsky’s four characteristics a patient must have to be safely watched. Are you saying the patient must have all four characteristics, or are you just saying that these are some of the factors that might contribute to a decision?

  2. There are no hard and fast rules. They are all variables to consider in shared decision-making.

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