Predicting Insignificant Prostate Cancer
Abstract & Commentary
By William B. Ershler, MD, Editor
Synopsis: In an effort to identify those individuals with indolent prostate cancers that may be best suited for a "watchful waiting" management strategy, Chun and colleagues compared pre-surgical data to the operative findings in 1132 consecutive patients with localized prostate cancer referred for surgery over an 11 year period. They constructed a nomogram including PSA dynamics, Gleason score, core (biopsy) cancer length, and percentage of positive biopsy cores which had 90% accuracy in predicting those patients with organ-confined cancer with a tumor volume of less than 0.5 cc and without Gleason 4 or 5 patterns. However, the nomogram had a low level of specificity with approximately half (depending on the various "cut-offs" used) identified as high-probability of insignificant prostate cancer (IPC) proving to have more aggressive patterns at the time of radical prostatectomy. Thus, such nomograms need to be employed with great caution as predictors of those with insignificant prostate cancer.
Source: Chun FKH, et al. Cancer. 2008,113:701-709.
Approximately 1 in 6 U.S. men will receive the diagnosis of prostate cancer in their lifetime, but for some its presence may be of little or no significance. Yet, prostate cancer accounts for about 30,000 deaths each year1 and prostate cancer death occurs primarily in older men. The median age at death is 80 years, and 71% of deaths due to prostate cancer occurred in men older than 75 years. Thus, prostate cancer occurs frequently, particularly in older men, but many, either because of more indolent disease, or because of comorbidities, will die of some other cause. Although a substantial portion of prostate cancer diagnosed by current screening methods will never cause symptoms (termed insignificant prostate cancer, [IPCa]), identifying those for whom aggressive intervention is necessary remains a challenge. This is evident from recent publications which indicate that those who progress during active surveillance ("watchful waiting") may have less favorable outcomes after radical prostatectomy.2
Chun and colleagues from the University of Hamburg in Germany examined an assessment tool (nomogram) designed to identify those patients with IPCa.
Over 11 years (1992-2003), 1132 patients with localized prostate cancer were referred for radical prostatectomy. The investigators performed a retrospective review to determine the capacity for pre-surgery measures to identify those with IPCa. A nomogram was developed incorporating known predictors including prostate-specific antigen (PSA), clinical stage, biopsy Gleason sum, core cancer length and percentage of positive biopsy cores (percent positive cores). The nomogram was compared to one previously published that had incorporated slightly different criteria.3 For the current nomogram, IPCa was defined as organ-confined PCa with tumor volume <0.5 cc and without Gleason 4 or 5 patterns. Finally, an external validation of the most accurate IPCa nomogram was performed in the same group.
Using these criteria, IPCa was pathologically confirmed in 65 (5.7%) men. Using statistical methodology (bootstrap correction) the predictive accuracy of the new nomogram was 90% vs 81% for a previously reported nomogram. However, in cutoff-based analyses of patients who qualified by the current and the older nomograms as high probability for IPCa, 63% and 45%, respectively, harbored aggressive PCa variants at the time of radical prostatectomy.
Thus, despite a high accuracy for identifying those predicted to have IPCa, both nomograms identified individuals as IPCa who were likely to be misclassified. The rate of misclassification is even further inflated when specific cutoffs are used. As a consequence, extreme caution is advised when statistical tools are used to classify a specific prostate as "insignificant."
Commentary
It is encouraging to know that strong efforts are being made to identify individuals likely to have indolent (or insignificant) prostate cancer but discouraging to recognize that established presurgical criteria are not yet sufficiently accurate to recognize all who are destined to have problematic disease. Accordingly, practitioners must rely on clinical judgment to determine which patients are best suited for a program of active surveillance and which would be best managed with early intervention.
The issue is unlikely to go away any time soon. In fact, with the aging population, and the prostate cancer incidence figures rising, we will be increasingly faced with this conundrum. In fact, the issue is coincident with new perspectives on prostate cancer screening. The United States Preventive Services Task Force (USPSTF) recently updated their guidelines for prostate cancer screening4 and have concluded that for men 75 years and older, there is now adequate evidence that the incremental benefits of treatment for prostate cancer detected by screening are small to none, whereas the harms, including erectile dysfunction, urinary incontinence, bowel dysfunction and death are substantial.5 Thus, USPSTF states that prostate cancer screening should not be routinely employed in this age group. In fact, for younger men, the task force pointed out that the evidence remains insufficient to assess the benefits and harms, and therefore offers no specific recommendation. Nonetheless, most major U.S. medical organizations agree that the appropriate screening candidates are those over the age of 50 years with a life expectancy of at least 10 years.6-9
References
1. Jemal A, et al. Cancer statistics, 2007. CA Cancer J Clin. 2007;57(1):43-66.
2. Klotz L. Active surveillance for prostate cancer: for whom? J Clin Oncol. 2005;23(32) 8165-8169.
3. Kattan MW, et al. Counseling men with prostate cancer: a nomogram for predicting the presence of small, moderately differentiated, confined tumors. J Urol. 2003;170(5):1792-1797.
4. Screening for prostate cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2008; 149(3): 185-191.
5. Lin K, et al. Benefits and harms of prostate-specific antigen screening for prostate cancer: an evidence update for the U.S. Preventive Services Task Force. Ann Intern Med. 2008;149(3):192-199.
6. Screening for prostate cancer. American College of Physicians. Ann Intern Med. 1997;126(6):480-484.
7. Prostate-specific antigen (PSA) best practice policy. American Urological Association (AUA). Oncology. (Williston Park) 2000;14(2):267-72,277-8,280 passim.
8. Lim LS, Sherin K: Screening for prostate cancer in U.S. men. ACPM position statement on preventive practice. Am J Prev Med. 2008;34(2):164-170.
9. Smith RA, et al. American Cancer Society guidelines for the early detection of cancer, 2006. CA Cancer J Clin. 2006;56(1):11-25;quiz49-50.
In an effort to identify those individuals with indolent prostate cancers that may be best suited for a "watchful waiting" management strategy, Chun and colleagues compared pre-surgical data to the operative findings in 1132 consecutive patients with localized prostate cancer referred for surgery over an 11 year period.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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