The Challenge of Comparing Investigative Approaches to Prostate Cancer

The article by Polascik and coauthors provides a timely synopsis of modern technologic advances in prostate cryoablation and a review of the rationale for and experience with targeted prostate treatments. Prostate cryoablation has a storied past, which can be briefly summarized as high excitement followed by near-complete abandonment. Fortunately, a few practitioners improved the technique and incorporated new technologies allowing for its resurrection. The authors mention a few improvements in a third-generation device, but numerous others have made prostate cryoablation much more safe and user-friendly, most notably the improvement in transrectal ultrasound imaging. The hope is that with larger cohorts and/or prospective studies this procedure will be on par with the mainstays of treatment for clinically localized prostate cancer.

One of Many Targeted Treatments

A controversial and important theme of the article is the evolution to prostate hemiablation or even targeted focal treatment. This concept of the “male lumpectomy” has gained momentum largely because the side effects of standard treatments leave much to be desired. The authors highlight the feasibility of these techniques from the very limited published experience.

It is worth noting that this technology is one of many that hold promise in this area. While cryoablation is perhaps in the most advanced state of use, many others are being studied vigorously (targeted high-intensity focused ultrasound, targeted delivery of radiation, vascular targeted photodynamic therapy, radiofrequency ablation, interstitial self-regulating thermal rods, and irreversible electroporation). While these modalities are typically used for whole-gland treatment, they have the potential to be used for targeted ablation.

In an environment where evidence is critical and resources are limited, the main issue in developing these technologies is how to do it responsibly. The least desirable outcome is a hodgepodge of noncomparable data, which does little to service oncology patients. This would make the already murky discussion about the best treatment for clinically localized prostate cancer even more difficult.

Two Problems

Two very important problems hamper the development of responsible outcomes research in targeted treatments of prostate cancer. The authors address one problem superficially and the other unsatisfactorily.

First, with the phenomena of multifocality and indolence, are all tumors clinically significant and therefore requiring treatment? The importance of determining biologic potential cannot be overemphasized, but this creates practical problems in outcomes research. Barring a major unanticipated advance, prostate-specific antigen (PSA) measurement and repeat prostate biopsy will almost certainly be the means by which oncologic efficacy will be assessed, provided these technologies are to be approved by an organization such as the US Food and Drug Administration. PSA will be a poor indicator, as significant portions of the prostate gland remain intact in targeted treatments. How can oncologic efficacy be assessed if a patient‘s initial multifocality or laterality is poorly understood? This would seemingly require that only hemiablation or targeted treatment be performed on patients with known unilateral disease, and most current staging modalities are insufficient for assessing this approach.

The second problem is how to adequately stage patients. As an analog, breast cancer tends to be unifocal and can be adequately identified with imaging, allowing for organ-sparing surgery. Prostate cancer management does not have these advantages. Magnetic resonance imaging and color Doppler ultrasonagraphy with real-time elastography do not have the sensitivity to detect small satellite tumors.[1] A strategy of transperineal extended prostate biopsies with a brachytherapy grid at 5-mm increments has more sensitivity in determining the laterality of cancers and is probably the more appropriate screening procedure for inclusion of patients in trials for targeted treatments.[2] Unfortunately, this procedure can be quite tedious, but it can offer many secondary advantages for men with low-volume, low-grade prostate cancer. With more accurate staging and grading, patients may opt for a more traditional therapy or may feel more secure with a watchful waiting strategy.

Conclusions

The authors are to be commended on the work that they have done to advance knowledge in this area. The challenge is to develop a means of investigating cryoablation as well as other technologies in a cohesive and comparable manner. While there will certainly be “winners” and “losers,” the hope is that a deliberate and guided effort would foster improvement in the delivery of ablative technologies in a way that would ultimately benefit men suffering from prostate cancer.

The main article can be found here:

From Whole-Gland to Targeted Cryoablation for the Treatment of Unilateral or Focal Prostate Cancer

Disclosures:

Financial Disclosure:The authors have no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.

References

1. Sumura M, Shigeno K, Hyuga T, et al: Initial evaluation of prostate cancer with real-time elastography based on step-section pathologic analysis after radical prostatectomy: A preliminary study. Int J Urol 14:811-816, 2007.
2. Crawford ED, Wilson SS, Torkko KC, et al: Clinical staging of prostate cancer: A computer-simulated study of transperineal prostate biopsy. BJU Int 96:999-1004, 2005.