No abstract

Focal cryoablation can provide biochemical and local control of prostate cancer while preserving potency and continence. Further investigation is needed.

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’.

BACKGROUND: Localized prostate cancer can be treated several different ways, but head-to-head comparisons of treatments are infrequent. The authors of this report conducted a randomized, unblinded, noninferiority trial to compare cryoablation with external beam radiotherapy in these patients. METHODS: From December 1997 through February 2003, 244 men with newly diagnosed localized prostate cancer were assigned randomly to receive either cryoablation or radiotherapy (122 men in each arm). All received neoadjuvant antiandrogen therapy. The primary endpoint was disease progression at 36 months based on a trifecta definition: 1) radiologic evidence of metastatic disease, or 2) initiation of further antineoplastic therapy, or 3) biochemical failure. Two definitions of biochemical failure were used: 1) 2 consecutive rises in prostate-specific antigen (PSA) with a final value >1.0 ng/mL, and 2) a rise above PSA nadir þ 2 ng/mL. Secondary endpoints included overall survival, disease-specific survival, and prostate biopsy at 36 months. RESULTS: The median follow-up was 100 months. Disease progression at 36 months was observed in 23.9% (PSA nadir þ 2 ng/mL, 17.1%) of men in the cryoablation arm and in 23.7% (PSA nadir þ 2 ng/mL, 13.2%) of men in the radiotherapy arm. No difference in overall or disease-specific survival were observed. At 36 months, more patients in the radiotherapy arm had a cancer-positive biopsy (28.9%) compared with patients in the cryoablation arm (7.7%). CONCLUSIONS: The observed difference in disease progression at 36 months was small, 0.2%; however, because of the wide confidence interval, from À10.8% to 11.2%, it was not possible to rule out inferiority (defined a priori as a 10% difference). With longer term follow-up, the trend favors cryoablation. Significantly fewer positive biopsies were documented after cryoablation than after radiotherapy. Cancer 2010;116:323-30.

Biochemical and local control rates support the use of salvage cryoablation for localized recurrence following failed radiation therapy. Efforts to continue to minimize these complications and to improve disease control in patients with persistent cancer following definitive radiotherapy should continue.