THE "NEW" PROSTATE CANCER INFOLINK

We had previously posted a brief comment on a paper by Mearini et al., who had reported on Italian experience of the use of high-intensity focused ultrasound (HIFU) in the treatment of localized prostate cancer. An editorial now accessible on the UroToday web site provides us with additional insights on this paper (originally published in the January issue of the Journal of Urology). It provides both good news and less good news.

Mearini and and his colleagues reported on their experience using the Sonoblate 500 in the treatment of 163 prostate cancer patients. Theirs was a prospective study of 163 patients with clinical stages T1-T3N0M0. A prostate volume >50 cm³ and certain other characteristics were predetermined exclusion criteria. None of their patients underwent TURP or neoadjuvant androgen deprivation therapy prior to HIFU. Treatment was carried out under spinal or general anesthesia in a day-surgery suite, but patients were kept overnight; they were then discharged with 3 weeks of antibiotics and anti-inflammatory agents. Urinary symptoms were evaluated by the IPSS questionnaire and sexual function by the IIEF-5 questionnaire. All patients received a follow-up, eight-core prostate biopsy after 6 months. Biochemical failure was defined using the Phoenix criteria (nadir PSA + 2 ng/ml).

Patient characteristics were as follows:

• The median patient age was 72 years and median PSA was 7.3 ng/ml.
• Clinical stage was T1 in 72 patients (44.1 percent), T2 in 69 patients (42.5 percent), and T3 in 22 patients (13.4 percent).
• Gleason biopsy score was between 5 and 7 in 76.7 percent of patients.
• D’Amico classification stratified patients as low risk in 80 men, intermediate risk in 47, and high risk in 14. The report itself classified 22 men with stage T3a disease as very high risk.
• Other pretreatment parameters included the median prostate volume (32.4 cm³), median maximum urinary flow rate (12 cm³/sec), median IPSS (10), and median IIEF-5 (16).
• The Foley catheter or supra-pubic tube was removed at a median of 13 days.
• Median follow-up was 23.8 months and 3 men were lost to follow-up.

The results of the study demonstrated the following:

• Of the 163 patients enrolled, 28 (17.2 percent) were given a second HIFU treatment (usually as a consequence of prostate size or residual tumor).
• One patient was reported to have a rectal fistula 2 months after HIFU.
• Median PSA nadir was 0.15 ng/ml, reached at a median time of 2.3 months.
• In men undergoing a single treatment, the 6-month positive biopsy rate was 33.9 percent and regression analysis showed that a PSA nadir >0.4 ng/ml had an independent predictive value for local failure.
• Negative biopsy rates for low, intermediate, high, and very high-risk patients were 75.6, 77.4, 35.7, and 18.7 percent, respectively.
• Biochemical disease-free status was observed in 125/160 men (78.1 percent).
• Independent predictive value for biochemical relapse included a PSA nadir >0.4 ng/ml and risk stratification.
• Three-year biochemical-free survival rates for low, intermediate, high and very high-risk patients were 86.1, 79.6, 56.4, and 19.6 percent, respectively.
• Maximum urinary flow rates at 6 months improved 25 percent from baseline to 16 cc/sec and IPSS decreased 30 percent to a median of 7.
• Urinary incontinence was uncommon, but 15 percent of patients developed urethral stricture.

These data would appear to suggest that HIFU may be a reasonable form of treatment for men with low and intermediate risk prostate cancer and a relatively small prostate, but that patients at high risk for progression are not appropriate candidates for this form of treatment. It is important to note that patients in this studydid not receive a pre-HIFU TURP or androgen deprivation therapy (forms of pre-HIFY therapy that have ben common in other trials).

The 25 percent positive biopsy rate in low risk patients at the 6-month follow-up period is still problematic, however, and will need to be carefully compared to outcomes using current standard options as HIFU goes forward. There is also the fundamental issue of how many of these men might be better managed with active surveillance on the grounds that they may never need intervention for prostate cancer (although they may need treatment for an enlarged prostate).