High-intensity focused ultrasound for prostate cancer: comparative definitions of biochemical failure

OBJECTIVES To compare the specificity and sensitivity of different definitions of biochemical failure in patients treated with high-intensity focused ultrasound (HIFU) for prostate cancer, to identify the most accurate predictor of clinical failure after HIFU. PATIENTS AND METHODS Consecutively treated patients who underwent HIFU between October 1997 and July 2006 at two centres (Lyon, France; and Regensburg, Germany) were prospectively maintained within a central database and retrospectively reviewed for this study. Clinical failure was defined as a positive prostate biopsy after treatment, radiographic evidence of lymphatic or bony metastatic disease, or salvage treatment for prostate cancer (surgery, radiation, hormonal therapy or second HIFU). The serum prostate-specific antigen (PSA) values after HIFU were assessed as a biochemical surrogate of a therapeutic success or failure. PSA threshold values, 'PSA nadir plus', PSA velocity, PSA doubling time and the American Society or Therapeutic Radiotherapy and Oncology and Phoenix definition of biochemical failure were all considered. The sensitivity, specificity, positive predictive value and negative predictive value of each biochemical definition for predicting clinical failure were determined. RESULTS The data from 285 patients (stage < T2, PSA < 15 ng/mL, Gleason score < 7) were analysed. The median (range) follow-up was 4.7 (2-10.9) years. The median PSA nadir was 0.13 ng/mL, which occurred at a median of 12.9 weeks after HIFU, and the median PSA at the last follow-up was 0.76 (1.6-2.7) ng/mL. Clinical failure occurred in 71 patients (25%); 24 due to a positive biopsy and 47 through the use of an additional therapy. Biochemical events that best predicted clinical failure were 'PSA nadir plus' values of 1.1-1.3 ng/mL, PSA velocities of < 0.3 ng/mL/year and PSA doubling times of 1.25-1.75 years. CONCLUSION A new definition of biochemical failure that is specific to patients treated with HIFU therapy is established, i.e. the 'Stuttgart definition', the 'PSA nadir plus 1.2 ng/mL'.