By: Dan Sperling, MD
It is impossible to exaggerate the importance of an accurate prostate cancer diagnosis, because it is the basis on which treatments are chosen. The need to match the treatment with the degree of the cancer’s danger arises from the need to avoid “undertreating” an aggressive cancer, and “overtreating” an indolent cancer that is less likely to become life threatening. The impact of overtreatment on patient quality of life (urinary and sexual side effects) is well documented in published clinical literature.
The fear of those side effects influences patients’ desire to choose as minimal a treatment as possible. In fact, many patients decide to hold off on treatment altogether, in favor of Active Surveillance (AS), if it appears that they have early stage, low risk cancer.
Historically, patients have been evaluated as candidates for AS based on the results of a systematic TRUS biopsy. Twenty years ago, such biopsies involved a mere six cores (sextant biopsy), three from each side of the gland. In 1994, Epstein et al published criteria for determining if biopsy-proven prostate cancer, based on TRUS biopsy, qualified patients to defer treatment while monitoring for disease progression. [i] The Epstein standards were Gleason score of 6 or less, two or fewer positive cores, and less than or equal to 50% of all cores. Arguably, if TRUS biopsies, especially sextant biopsies, were up to the task of accurately identifying the cancer, patients whose disease fit the Epstein criteria could safely defer treatment. Two recently published studies comparing the pathology results of TRUS vs. MRI-guided biopsies point to the hazard of relying on TRUS biopsy to qualify patients for AS.
The first study, out of UCLA, calls into question whether the Epstein criteria still apply to patients considering AS.[ii] Because the 1994 standards were based on TRUS biopsy, the authors hypothesized that MRI-guided targeted biopsy would produce a more accurate profile of a given man’s prostate cancer. They identified 113 men with biopsy-proven prostate cancer who were enrolled in an AS program. An average of 10 months after diagnosis, each study participant had a 4-core targeted biopsy guided by multiparametric MRI (mpMRI), with suspicious areas assigned values from 1-5 based on appearance of aggression (5 being most aggressive.) In addition to the targeted biopsy, each patient also had a 12-core repeat TRUS biopsy. According to the total biopsy results, 33.6% of the men appeared to have no prostate cancer; 31% fulfilled the Epstein criteria; and 36.3% exceeded the Epstein criteria, implying that they were not candidates for AS. The authors concluded that the use of mpMRI should call into question the Epstein criteria as a means for determining a patient’s suitability for AS.
The second study was published several months earlier in the journal European Urology by a team largely out of the National Cancer Institute/National Institutes of Health.[iii] This prospective study enrolled 582 participants between 2007-12 to compare between systematic 12-core TRUS biopsies and targeted MRI/ultrasound fusion-guided biopsies performed during the same biopsy session. The highest Gleason score from each biopsy method was compared. 315 of the enrollees (54%) were found to have prostate cancer. The targeted biopsy results led to upgrading of the Gleason score in 81 cases (32%). According to the article:
Targeted biopsy detected 67% more Gleason > 4+3 tumors than 12-core biopsy alone and missed 36% of Gleason < 3+4 tumors, thus mitigating the detection of lower-grade disease…Targeted biopsy technique preferentially detects higher-grade PCa while missing lower-grade tumors.
Taken together, these two articles are instructive for patients considering AS based on a 12-core TRUS biopsy. It is essential that the presence of high grade prostate cancer be definitively ruled out before a program of AS begins. Unlike prostate ultrasound, which is “blind” to prostate tissue differences, the ability of mpMRI to delineate regions of high grade suspicion allows selective tissue sampling in those areas. When a higher grade turns out to be the case, Leonard Marks (a co-author of the UCLA study) aptly calls this “risk inflation.”[iv] The danger of embarking on a program of AS with unidentified Gleason 4 disease, or more extensive disease than detected on TRUS biopsy, leaves a patient at risk of missing a window for successful localized treatment. With the increasing accessibility of mpMRI, no patient should be left in that position.
 Epstein J, Walsh P, Carmichael M, Brendler C. Pathologic and clinical findings to predict tumor extent of nonpalpable (stage T1c) prostate cancer. JAMA. 1994 Feb;271(5):368-74.
 Hu JC, Chang E, Natarajan S, Margolis DJ et al. Targeted prostate biopsy to select men for active surveillance: do the Epstein criteria still apply? J Urol. 2014 Feb 8. doi: 10.1016/j.juro.2014.02.005. [Epub ahead of print]
 Siddiqui M, Rais-Bahrami S, Truong H, Stamatakis L et al. Magnetic resonance imaging/ultrasound-fusion biopsy significantly upgrades prostate cancer versus systematic 12-core transrectal ultrasound biopsy. Eur Urol. 2013;64:713-719.
 Lyford, Joanna. Prostate biopsy method impacts cancer risk profile. Jun 5, 2014. http://www.news-medical.net/news/20140605/Prostate-biopsy-method-impacts-cancer-risk-profile.aspx.