Adjuvant Hormone Blockade (HB) after Surgery for Men with Aggressive Disease

BY MARK SCHOLZ

The term "adjuvant" means treatment “added to” the primary or initial treatment. When the primary treatment is surgery, even when all detectable disease is removed, there remains a statistical risk that the cancer will return due to microscopic cancer cells left behind. Men with high-risk features such as extra-prostatic extension or high Gleason score face a higher risk of recurrence.

We need to understand the rationale for considering hormone blockade (HB) in treating aggressive prostate cancer. However, the scientific studies supporting this approach are still preliminary. Patients who have aggressive prostate cancer now are forced to make the best treatment decision possible with the data currently available.

In May 2011 the Journal of Clinical Oncology, Dr. Tanya Dorff and others reported on 351 men, average age 60, who were treated with two years of Casodex & Zoladex initiated immediately following surgery. The average PSA prior to surgery for men in the study was 7.8. PSA had to be less than 0.2 after surgery to be eligible for participating in the study. After completing two-years of hormone blockade half the men recovered normal testosterone within a year. By 18 months, 89% had recovered. After five years, relapse free survival rates of over 90% are impressive for these high risk patients where “high risk” is determined by historical relapse rates that approach 50%.

Almost all previous studies evaluating the benefit of adding HB to surgery showed no benefit. The resultant lack of benefit was probably due to the very short duration of HB—usually for only three months. There is one study by Dr. Martin Gleave at Vancouver General Hospital, comparing three months with eight months of HB after surgery, and showing a slightly better outcome for men with aggressive disease when HB was continued eight months.

The most compelling previously published study of adjuvant HB, authored by Edward Messing was performed in 98 men with proven node metastasis, half of whom received immediate HB.  In the case of men who did not get adjuvant HB, the relapse rate was quadrupled.

Adding HB to radiation for men with bad prognostic factors is standard because several large randomized prospective trials show that HB reduces relapse rates and prolongs survival. Given these indisputable benefits, it is surprising that a similar study to evaluate the benefit of longer duration HB after surgery has never been undertaken.

Long-term HB after surgery results in a much lower incidence of PSA progression compared to historical PSA relapse rates that have been reported in multiple studies. However, actual proof that long-term hormone blockade after surgery will enable men to live longer will require a randomized prospective trial.  The table below lists the projected five year outcome in the study by Dorff et al. depending on the different stages of the men participating in the study.

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