BERKELEY, CA (UroToday.com) - The emergence of active surveillance as a viable management option for purported early stage prostate cancer is based on the hypothesis that insignificant or minimal cancer, despite lacking a universally accepted definition, is both common within any given population and is frequently detected by current diagnostic techniques.
With this assumption, many nomograms have been designed to identify patients with probable insignificant disease and more recently patients who would be suitable for active surveillance. The reported high accuracy of such nomograms 73%-90%1 is in reality directly related to the ability to identify and exclude significant disease rather than the ability to identify insignificant cancer. The accuracy is also biased in that insignificant cancer is rare (3-6%) in the historic radical prostatectomy series on which these nomograms are based.[2,3] Further, formulae-based nomograms[2,3] incorporate a level of stringency (25%) or strictness designed to offer the greatest accrual while still maintaining an acceptable positive and negative predictive value.
There is currently much debate regarding the precise definition of insignificant cancer[4,5] with respect to cancer volume and whether minor elements of Gleason pattern 4 are permissible. There is, however, little debate as to what constitutes a "high risk" cancer where active surveillance is not a management option.
With these issues in mind, we propose that early stage prostate cancer be separated into 3 groups; insignificant cancer (original definition by Stamey4), significant cancer, and "high-risk" cancer.[1] This separation is based on the recognition that the definition of insignificant cancer is imprecise and it is likely that many so-called significant cancers may be clinically insignificant in some individuals. We therefore developed a pre-operative nomogram that is more accurate than currently published nomograms, which in addition to identifying men likely to have insignificant cancer, also estimates their associated chance of having an unrecognised "high-risk" cancer. In addition, we incorporate the concept of "variable nomogram stringency," that will allow the end user flexibility to adjust these results to best fit the patient with respect to age, comorbidities, and overall life expectancy.
It is clear that much overlap exists between insignificant and significant cancer, and rather than focus on defining the precise break point of a continuum, we propose that this nomogram be used to predict the ends of the spectrum (insignificant disease suitable for active surveillance, and high-risk disease for active intervention). This strategy, coupled with the adjustable stringency that our nomogram offers, will greatly improve individual application. Possibly the greatest value of this nomogram is in identifying individuals with an unacceptable chance of "high-risk" cancer - even among those men already in surveillance programs - that will allow us to terminate surveillance and direct these men towards active intervention.
References:
- O’Brien BA, Cohen, RJ, Ryan A, Sengupta S and Mills J. A new preoperative nomogram to predict minimal prostate cancer: Accuracy and error rates compared to other tools to select patients for active surveillance. J Urol 2011; 186: 1811-1817.
- Kattan MW, Eastham JA, Wheeler TM, Maru N, Scardino PT, Erbersdobler A, et al. Counseling men with prostate cancer: a nomogram for predicting the presence of small, moderately differentiated, confined tumors. J Urol 2003; 170:1792.
- Chun FK, Haese A, Ahyai SA, Walz J, Suardi N, Capitanio U, et al. Critical assessment of tools to predict clinically insignificant prostate cancer at radical prostatectomy in contemporary men. Cancer 2008; 113:701.
- Stamey TA, Freiha FS, McNeal JE, Redwine EA, Whittemore AS and Schmid HP. Localized prostate cancer. Relationship of tumor volume to clinical significance for treatment of prostate cancer. Cancer 1993; 71 (3 Suppl):933.
- Epstein JI, Walsh P, Carmichael M and Brendler CB. Pathologic and clinical findings to predict tumor extent of nonpalpable (Stage T1c) prostate cancer. JAMA 1994; 271:368.
Written by:
Ronald J. Cohen, MBBCH, FFPATH, FRCPA, PhD as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
UroToday.com Prostate Cancer Section