Evaluating the need for immediate, adjuvant radiation therapy after surgery


Men with high-risk, localized prostate cancer who decide on surgery as their first-line treatment of choice are sometimes faced with the question of whether to undergo “immediate” adjuvant radiation therapy after their surgery or to do nothing and wait to see if salvage radiation therapy becomes necessary.

The things that can suggest a need for “immediate” adjuvant radiation (i.e., within about 4 months after surgery) include extracapsular extension, seminal vesicle invasion, and positive surgical margins (i.e., clear signs of pT3 disease), especially in a patient who originally met D’Amico criteria for classification as intermediate or high risk at the time of diagnosis.

As noted by Ost in a “Beyond the Abstract” commentary on the UroToday web site (and elsewhere in this blog), this remains an area of great controversy in the management of prostate cancer. Even for the most expert physician, it can be hard to know exactly what to recommend to an individual patient.

Three major, ongoing clinical trials are expected to help us in addressing this area of controversy:

  • The RADICALS study (being carried out in the UK) is designed to assess the timing of radiotherapy and the use of hormone therapy in conjunction with postoperative radiotherapy in men considered to need immediate hormone therapy, men considered to be suitable for observation, and men for whom that decision is uncertain.
  • GETUG-17 (being carried out in France) is designed to compare the effectiveness of immediate adjuvant radiation and hormonal therapy after radical prostatectomy to radiation and hormonal therapy at biochemical relapse.
  • The RAVES study (being carried out in Australia and New Zealand) is designed to compare the rates of biochemical failure following immediate adjuvant radiation as compared to active surveillance and early salvage radiation (when the patients’ PSA levels reach 0.2 ng/ml).

All three of these studies are still enrolling patients at this time, so it will be a while before data are available.

In the meantime, however, there has been only one (flawed) trial that offers definitive “level 1” evidence of improved clinical outcomes from immediate, adjuvant radiation therapy compared to observation followed by salvage radiation therapy as needed in high-risk patients after radical prostatectomy: the SWOG 8794 trial.

SWOG 8794 — first reported in 2006, with updated data reported in early 2009 — showed an average (median) overall survival benefit of 1.7 years for adjuvant radiation compared to salvage radiation at a follow-up of 12.6 years. (It was “flawed” to the extent that it never was able to enroll anything like the numbers of patients originally planned for.) Analysis of data from this study has also shown, at 12.6 years of follow-up,  that:

  • The average (median) metastasis-free survival benefit for adjuvant radiation was 2.2 years.
  • 70/211 patients (33.2 percent) in the observation arm of this trial actually needed salvage radiation therapy.
  • Hormone therapy was considered necessary in twice as many patients in the observation arm of the trial compared to the immediate adjuvant radiation arm of the trial.
  • To prevent each prostate cancer-specific death, 9.1 patients need to receive immediate adjuvant radiation.

Thus, despite the clear survival benefit of immediate adjuvant radiation therapy, a significant percentage of patients with high-risk pT3 prostate cancer are actually cured after radical prostatectomy, and therefore have no need of adjuvant radiation (and the risk for concomitant side effects of that radiation).

The other factor that is important in all of this is the fact that the quality of radiation therapy has been massively improved since 1987, when SWOG 8794 was initiated.

In August this year, Ost et al. reported data from a carefully matched case analysis comparing data from patients treated with  immediate high-dose adjuvant intensity-modulated radiotherapy (A-IMRT) with data from patients who received salvage IMRT (S-IMRT) when their PSA levels reached 0.2 ng/ml after prior careful observation. Patients were matched in a 1:1 ratio according to preoperative PSA level, Gleason score, and pT stage.

The results of this study were as follows:

  • 144 patients with high-risk disease at prostatectomy were referred for A-IMRT (median dose 74 Gy).
  • 134 patients with high-risk disease at disease were referred for S-IMRT (median dose 76 Gy) at biochemical recurrence
  • 178/278 were matched (89:89).
  • Average (median) follow-up was 36 months from the end of radiotherapy for both groups.
  • Based on time from the end of radiotherapy, the 3-year biochemical recurrence-free survival rates were
    • 90 percent for the A-IMRT group of patients.
    • 65 percent for the S-IMRT group of patients.
  • On multivariate analysis, based on time from the end of radiotherapy, S-IMRT, a Gleason grade of 4 + 3 = 7 or higher, perineural invasion,  a preoperative PSA level ≥10 ng/ml, and omission of androgen deprivation (AD) were all independent predictors for a reduced rate of biochemical recurrence-free survival.
  • Average (median) follow-up from completion of surgery was 43 months for the A-IMRT group of patients and 60 months for the S-IMRT patients.
  • Based on time from completion of surgery, the 3-year biochemical recurrence-free survival rates were
    • 91 percent for the A-IMRT group of patients
    • 79 percent for the S-IMRT group of patients.
  • On multivariate analysis, based on time from the completion of surgery, a Gleason grade of 4 + 3 = 7 or higher, perineural invasion, and omission of AD (but not S-IMRT and not a preoperative PSA level ≥10 ng/ml) were independent predictors for a reduced rate of biochemical recurrence-free survival.

There is growing evidence that “immediate,” adjuvant radiation therapy is a potentially better choice than observation followed by salvage radiation therapy for high-risk patients after first-line radical prostatectomy. However, this is still going to be a hard choice for each individual patient, and we desperately need more data to clarify

  • Which patients are most likely to benefit from taking immediate action as opposed to deferring their decision.
  • Whether there is a definable subset of patients for whom deferring therapy makes little to no difference.

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Google photo

You are commenting using your Google account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s

This site uses Akismet to reduce spam. Learn how your comment data is processed.

%d bloggers like this: