Research sets stage for subtotal focal ablation of prostate cancer

Key Points

Orlando, FL-As ablative technologies have matured to the stage where they can be used for precise tissue destruction, there has been increasing interest in subtotal focal therapy for prostate cancer as a means for minimizing treatment-related morbidity.

At the AUA annual meeting, researchers from New York University (NYU) and the University of Texas M.D. Anderson Cancer Center, Houston, reported the results of studies they undertook based on the premise that men with unilateral disease on prostate biopsy would represent the best candidates for subtotal ablative treatment.

The study from NYU compared disease features and cancer control outcomes after radical prostatectomy among men with final pathology-proven unilateral versus bilateral disease. It was based on a chart review of 1,458 consecutive patients operated on by a single surgeon between January 2000 and June 2007. The final pathology showed 311 men had unilateral disease and 1,147 had bilateral disease.

"These findings suggest that patients with low-risk prostate cancer, whether unilateral or bilateral, may be considered for focal therapy," said Basir Tareen, MD, a urologic oncology fellow at NYU working with Samir Taneja, MD, and colleagues. "Candidate selection for focal therapy should be based on risk stratification, but the method of focal therapy (hemiablative, subtotal, or lesion-targeted therapy) should be based on focality. Better imaging techniques and prognosticators for identifying low-risk patients are needed before this can become a reality."

The patients with bilateral and unilateral prostate cancer were similar with respect to age, biopsy, Gleason score, PSA, and positive surgical margin rates. However, compared with the men having bilateral cancer, the unilateral group had significantly lower rates of extracapsular extension (13% vs. 21%), seminal vesicle invasion (2% vs. 7%), and Gleason score ≥7 (42% vs. 51%). In addition, after a median follow-up of 36 months, the bilateral group had a significantly higher rate of biochemical recurrence compared with the unilateral group (16.7% vs. 8.3%), as well as a significantly shorter time to PSA recurrence (6 vs. 12 months).

There was no significant difference in recurrence-free survival rates between patients with unilateral versus bilateral low-risk tumors or between patients with unilateral versus bilateral high-risk tumors.

Investigators from M.D. Anderson evaluated the pathologic findings in prostatectomy specimens from patients found to have unilateral prostate cancer on biopsy. The study was undertaken to plan for a prospective trial of subtotal focal ablation of the prostate and involved 180 men who underwent radical prostatectomy subsequent to extended, laterally directed prostate biopsy showing unilateral, multi-site, positive cores.

Two templates for subtotal focal therapy-an ipsilateral hemispheric approach and an anterior-winged, 3/4 hockey stick template-were applied to the specimens, and the results were analyzed to determine how well each technique targeted the tumor foci.

The results showed undetected prostate cancer and multifocality were prevalent despite extended prostate biopsy. Of the 180 men, 83% had bilateral disease in the prostatectomy specimen, and in 66% of men, the dominant tumor focus was ipsilateral to the unilaterally positive biopsy site. The hockey stick template increased capture of tumor foci and appeared theoretically capable of eradicating 100% of dominant tumors and the vast majority of clinically significant tumors.

"Subtotal focal ablation aims to minimize side effects of prostate cancer treatment," said first author John F. Ward, III, MD, assistant professor of urology at M.D. Anderson. "Since presently we are not able to identify which cancers are biologically significant and likely to progress, our hope is that we can have our cake and eat it too by using this approach to effectively eradicate the cancer and avoid overtreatment in order to preserve quality of life.

"Our findings about the utility of the hockey stick template are encouraging, but this is a retrospective study in a selected group of men. In addition, it assumes cryoablation achieves complete eradication of tumor, which may be an overestimate, especially considering that some men in our series had high-risk features. A prospective trial comparing the templates will soon be under way to provide more definitive answers about the efficacy and safety of these approaches to subtotal focal cryoablation."

Dr. Ward reported that with application of a hemiprostate ablation template, the treatment field would encompass all cancer in only 17% of men, although clinically significant cancer (excluding low-volume/low-grade foci) would be targeted in 64% of men, and dominant (index) tumor would be treated in 89% of men. The hockey stick template increased in-field capture rates to 47% for all tumor foci, 81% for all clinically significant cancer, and 100% for all dominant tumors.

One of the co-authors on the M.D. Anderson study is a consultant/adviser to Endocare.