When Biochemical Failure Does Not Mean Cancer Recurrence in Men Treated by External Beam Radiotherapy and Adjuvant Hormones for Intermediate Risk Prostate Cancer

Abstract

Biochemical recurrence following prostate cancer radiotherapy is the accepted barometer of treatment failure and is used to guide clinical management in a given patient as well as to compare the relative efficacy of different treatments. As normal prostatic acini recover from radiotherapy, they secrete PSA even though all the cancer in the prostate may have been eradicated. Knowledge about when such PSA increases that meet the definition of biochemical failure but does not indicate cancer recurrence is important. To determine this rate we studied our mature institutional experience treating intermediate risk prostate cancer with external beam radiotherapy (EBRT). Materials/Methods: Our center serves a population of 1.3 million persons and is the sole provider of radiotherapy within our provincial local health region. A retrospective review of our experience with intermediate risk prostate cancer (PSA 10-20 and/or Gleason score 7 and/or T stage< T3) treated for cure with EBRT (with or without adjuvant hormones) and a minimum of 10 years since completion of the radiation was performed. Patient demographic, cancer, treatment, and subsequent clinical course details were abstracted from the electronic medical record. Biochemical failure status as per the Phoenix definition was determined. Among the patients with biochemical failure, clinical cancer recurrence was defined as the occurrence of any of the following:1) PSA >5, 2) initiation of hormonal treatment, 3) utilization of any salvage loco regional treatment, 4) clinical/imaging determination of local, regional or metastatic recurrence 5) unknown status. Results: Between 2002 and 2007 542 men were treated by a 3D CRT or IMRT EBRT technique to a median dose of 76 Gy in 38 fractions. Age ranged from 40 to 83 years (median 70) Median follow up was 76 months (range 3 to 191), 82.9% (449 patients) remain in remission, and 17.1% (93 patients) have developed biochemical failure. Among the patients with biochemical failure 15% (14 patients) have had no clinical cancer recurrence for a calculated actuarial probability of patients with biochemical failure actually NOT having clinical cancer of 19% at 5 years. Serum testosterone levels are available in 11 of these 14 patients. 9/11 had normal testosterone and 2/11 are hypogonadal. Conclusion: An appreciable proportion of patients with biochemical failure following EBRT for intermediate risk prostate cancer do not have clinical cancer recurrence. This 19% (an underestimate as a proportion of patients who had hormones initiated as soon as biochemical failure was diagnosed likely did not have cancer) presumably reflects recuperating benign prostatic epithelium and should be considered both when comparing the treatment efficacy of EBRT with other modalities and when contemplating initiation of hormones or local salvage treatments.