Improving the Early Detection of Prostate Cancer: A Balancing Act

The article by Crawford et al[1] in this issue of ONCOLOGY is especially timely given the controversy surrounding early detection of prostate cancer. Since the US Food and Drug Administration approval of prostate-specific antigen (PSA) testing in 1992, the practice of screening for prostate cancer in the United States has generally been based on age and has become relatively widespread. While the number of deaths from prostate cancer has decreased since the dawn of the PSA era, the relative contributions of screening and treatment-pattern changes are not known. One thing about screening is certain, however: it clearly results in overdiagnosis, and in many cases overtreatment, of prostate cancer. In one study it was estimated that prostate cancer was overdiagnosed in 29% of white males and 44% of black males.[2] The impact of age-based PSA screening of men 55 to 69 years old on prostate cancer mortality can be seen in the European Randomized Study of Screening for Prostate Cancer (ERSPC), in which an approximate 20% reduction in relative prostate cancer mortality was observed after 10 to 13 years of follow-up; to achieve this outcome requires a relatively large number of men to be screened (approximately 1,400) and a relatively large number of men to be diagnosed (about 45) and treated to prevent one cancer death.[3]

Improved early detection of prostate cancer would ideally involve a noninvasive test that allows clinicians to distinguish aggressive cancers from relatively indolent ones. This distinction is especially important given that relatively few men who undergo screening are destined to die of prostate cancer. It is worth considering that in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, the rate of death from ischemic heart disease was 17 times greater than that from prostate cancer, even though the patient population under study was, overall, healthier than people of similar age in the general US population.[4] The biomarkers reviewed by Crawford et al demonstrate the promise of potentially avoiding unnecessary biopsy in men who do not have an aggressive but asymptomatic prostate cancer or any prostate cancer at all. However, the benefit of avoiding biopsy may come at the cost of potentially missing some of the clinically relevant cancers that would otherwise be detected. This tradeoff must be thoroughly evaluated before widespread use of these new biomarkers can be established.

There are other approaches to improving early detection of prostate cancer: better biopsies and increased use of imaging. Conventional prostate biopsy is a relatively haphazard, random sampling of 12 biopsy cores irregularly distributed throughout the prostate gland. Biopsies performed in this way often miss significant prostate cancers and underestimate the true grade and stage of cancer, even when they are positive. In place of random biopsy, template-guided biopsy (transrectal or transperineal) has been shown to yield a higher prostate cancer detection rate overall, as well as more accurately graded and staged disease.[5] Moreover, template biopsies performed in an organized way can be used to direct subsequent re-biopsy for patients whose biopsies were atypical or who had abnormal DNA methylation, and who are undergoing active surveillance.[6]

Multi-parametric MRI scanning is another potential way to improve prostate cancer detection. In addition to assessing the stage of cancer, it can enable biopsies to be targeted to the most suspicious regions of the prostate. This strategy has the potential to identify the highest-grade cancers within the prostate.[7]

Finally, to improve the overall cost benefit of screening, urologists need to embrace active surveillance more frequently. The necessity of adding further biomarkers may help in this regard, but their overall efficacy has not been truly established. It is unknown what impact knowledge about the genetic/genomic profile of a prostate tumor may have on individual patient management, it is hoped that such data will emerge soon.

The new biomarkers reviewed by Crawford et al certainly are promising. Even in their absence, however, urologists can improve the detection and management of prostate cancer by performing better biopsies, by using either template or image-guided strategies, and by embracing active surveillance.

Financial Disclosure:Dr. Andriole serves as a consultant/advisor to Augmenix, Bayer, Genomic Health, GlaxoSmithKline, and Myriad Genetics, and he is an investigator for Johnson & Johnson, Medivation, and Wilex. Dr. Brockman 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. Crawford ED, Ventii K, Shore ND. New biomarkers in prostate cancer. Oncology (Williston Park). 2014:28:135-42.

2. Etzioni R, Penson DF, Legler JM, et al. Overdiagnosis due to prostate-
specific antigen screening. J Natl Cancer Inst. 2002;94:981-90.

3. Schröder FH, Hugosson J, Roobol MJ, et al. Prostate cancer mortality at 11 years of follow-up. N Engl J Med. 2012; 360:1320-8.

4. Andriole GL, Crawford ED, Grubb RL III, et al. Mortality results from a randomized prostate-cancer screening trial. N Engl J Med. 2009; 366:981-90.

5. Megwalu II, et al. Evaluation of a novel precision template-guided biopsy system for detecting prostate cancer. BJU Int. 2008;102:546-50.

6. Andriole GL, Bullock TL, Belani JS, et al. Is there a better way to biopsy the prostate? Prospects for a novel transrectal systematic biopsy approach. Urology. 2007;70:S22-6.

7. Somford DM, Hamoen EH, Fütterer JJ, et al. The predictive value of endorectal 3 Tesla multiparametric magnetic resonance imaging for extraprostatic extension in patients with low, intermediate and high risk prostate cancer. J Urol. 2013;190:1728-34.