The Promise of Targeted Therapy for Localized Prostate Cancer

January 1, 2007

The morbidities associated with prostate cancer treatments have improved over the years. However, potential overtreatment and the risks of adverse events associated with radical treatment still pose a considerable challenge. Targeted focal therapy (TFT) of prostate cancer appears to be part of a logical continuum in the quest to improve upon the management of early organ-confined disease. TFT is a procedure in which only the cancer in the gland is ablated. The normal gland, sphincter, and in most cases the neurovascular bundles are preserved. Therefore, this approach averts some of the common complications of more radical therapy. Initial experience has been encouraging; however, long-term data and full implementation of emerging advances in imaging are urgently needed before the widespread adoption of this approach. In this review, we present the current status of our knowledge about this procedure and the most important challenges that need to be addressed. We also present the initial results with this approach at our center.

The article entitled, "Targeted Focal Therapy: A Minimally Invasive Ablation Technique for Early Prostate Cancer," by Crawford and Barqawi, gives us a glimpse of what future therapy options relating to localized prostate cancer might look like. Currently, however, only radical surgery offers the hope of cure, with accompanying significant potential morbidity and even rarely —mortality.

Efforts to improve morbidity while maintaining good outcomes in prostate cancer patients have resulted in a variety of means to palliate an otherwise slow-growing malignancy, each associated with its own set of potential adverse effects. An ideal targeted treatment would include accurate staging and diagnosis, with therapy directed only at the malignant cells for a complete treatment effect. Although an ideal targeted treatment does not exist at present, Crawford and Barqawi propose a solution that is currently feasible using today's technology.

Transrectal ultrasound and prostate biopsy has long been the gold standard for diagnosis, and a larger number of cores performed at the time of biopsy has increased the likelihood of detecting prostate cancer. This has been particularly true in the transition zone, which is associated with more favorable outcomes. In targeted therapy, there is an imperative need to not only make a diagnosis, but to accurately determine each and every location of malignant tissue. Present imaging modalities therefore have a limited role in this setting, as they are unable to accurately detect and localize prostate cancer.

Accuracy of Staging

In prostate cancer where the disease process leads to a histologically infiltrative pattern, and which in many cases is a multifocal disease,[1,2] the accuracy of staging becomes more challenging. The presented staging technique in this paper involves systematically obtaining cores transperineally under ultrasound guidance using a grid pattern. The authors cite their experience with the grid pattern spaced at both 5 and 10 mm in autopsy and prostatectomy specimens. In both cases the smaller 5-mm grid increased the detection rate. However, no serial sections of the prostates were performed to determine the possibility of sampling error and missed disease, and the prostatectomy group included only 20 patients. Using this grid pattern, a 1-mm core, ranging in length from 10 to 15 mm, is taken every 5 mm in the closest spacing. This leaves the majority—or approximately 80% of tissue—unsampled and with significant potential for sampling error.

Value of Novel Therapies

The potential complications of cryoablation with third-generation equipment has improved significantly, and in one recent study of treatment for primary localized cancers, no patients developed a fistula, urinary retention occurred in 4%, persistent incontinence occurred in 4%, and erectile dysfunction in 86%.[3] Although early results suggest this technique is safe for treating primary cancers, the modality is presently still best suited for older and less fit patients.

Until a molecular basis for treatment becomes available, urologic oncologists will appreciate novel therapies such as this in their armamentarium. We can only hope that this and other minimally invasive targeted therapies will be as promising to prostate cancer as lumpectomy was to breast cancer. I look forward to longer-term follow-up and reported outcomes compared with contemporary localized cancer treatments.

—Chester C. Wilmott, MD

Disclosures:

The author has no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.

References:

1. Ruijter E, van Leenders G, Miller G, et al: Errors in histological grading by prostatic needle biopsy specimens: Frequency and predisposing factors. J Pathol 192:229-233, 2000.

2. Ruijter ET, Miller GJ, van de Kaa CA, et al: Molecular analysis of multifocal prostate cancer lesions. J Pathol 188:271-277, 1999.

3. Cresswell J, Asterling S, Chaudhary M, et al: Third-generation cryotherapy for prostate cancer in the UK: A prospective study of the early outcomes in primary and recurrent disease. BJU International 97:969-974, 2006.