By: Dan Sperling, MD

When prostate cancer (PCa) is diagnosed by biopsy, it is categorized by risk level based on a combination of clinical factors. Usually these include PSA, tumor stage and Gleason grade at the time of diagnosis. There are various models of risk assessment, but the most common is called the D’Amico classification:

• Low risk – PSA less than or equal to 10, Gleason score less than or equal to 6, stage T1-2a
• Intermediate risk – PSA 10-20, Gleason score 7, stage T2b
• High risk – PSA greater than 20, Gleason score equal to or higher than 8, stage T2c-3a

The D’Amico system has limitations because it is fairly simplified. As greater understanding of PCa develops, many experts believe it is important to take additional factors into account such as the number of positive biopsy needles, the greatest percentage of aggressive PCa in individual biopsy cores, and molecular or genomic analysis of the cell lines. The more complex the analysis, the more refined the classification. This has led to the idea of significant vs. insignificant prostate cancer (PCa). It is based, in part, on the observation that many cases of Gleason 3+3=6 PCa do not appear to progress rapidly, and some may never progress to a point of becoming potentially life threatening. Such cancers may be thought of as “insignificant,” and the most widely used definition is the Epstein criteria:

Tumor volume <0.2cm³, primary (first number) Gleason <6, and organ-confined

Anything above any of those standards is held to be significant. Patients with insignificant PCa are considered good candidates for Active Surveillance; or, those not comfortable with the idea of having to monitor cancer that might become dangerous over an indeterminate time period, may qualify for a focal treatment such as focal laser ablation (FLA).

Patients with significant PCa, on the other hand, are generally recommended for immediate treatment of an aggressive nature. While such interventions are almost always radical (prostatectomy or radiation), some patients with significant but unifocal tumors are turning to more aggressive focal therapy applications in hopes of sparing sexual and urinary function. The problem is, how can one be sure whether the tumor is significant or not?

This is where multiparametric MRI (mpMRI) on a powerful 3 Tesla (3T) magnet is a game-changer, and helps with treatment decisions. A recent study underscores how well 3T mpMRI performs in detecting significant PCa. Thompson et al. (2015) designed a study to correlate mpMRI results with both transperineal biopsies after imaging, and prostatectomy specimens (final pathology) after surgery.[i] This was an excellent, thorough study in terms of sample size (344 men analyzed), mpMRI using three parameters (T2 weighted, DWI and DCE-MRI), two different radiologists rating images using PI-RADS (https://sperlingprostatecenter.com/pi-rads-score/), and additional MRI-targeted biopsies as well as 30-core (average) perineal template biopsies. PI-RADS scores of 3-5 were considered positive for cancer, and significant prostate cancer was defined as any Gleason 7 with >5% Gleason 4 as part of the total grade. According to the authors, “The anatomical location, size, and grade of individual cancer areas in the 18-biopsy regions, as primary outcome, and in prostatectomy specimens (n=117), as secondary outcome, were correlated to the MRI-positive regions.” The study showed a high rate of match between MRI-positive regions and biopsy-positive regions; also, MRI-positive regions had a high rate of agreement with significant PCa found in RP specimens. In all, mpMRI detected significant PCa with 96% sensitivity, 36% specificity, 92% negative predictive value and 52% positive predictive value. The study concluded, “In men with abnormal PSA/DRE, mpMRI detected significant PC with an excellent NPV and moderate PPV. The use of mpMRI for diagnosing significant PC may result in a substantial number of unnecessary biopsies while missing minimum number of significant PC.”

The ability to rule out significant PCa can assist doctors and patients in holding off on a biopsy (with its risks of pain, infection and side effects) in favor of continuing to monitor using PSA and imaging—the basis for Active Surveillance. Advance image-based detection of areas suspicious for significant PCa permits an MRI-guided targeted biopsy, which minimizes the number of needles while maximizing accuracy. When doctor and patient have a high level of confidence in the diagnostic information, they can determine the optimum treatment match for the patient’s PCa, including focal treatment.

While the significant/insignificant classification remains an open topic of debate, mpMRI takes much of the “educated guesswork” out of detection, diagnosis and treatment.

[i] Thompson JE, van Leeuwen PJ, Moses D, Shnier R et al. The Diagnostic Performance of Multiparametric Magnetic Resonance Imaging to Detect Significant Prostate Cancer. J Urol. 2015 Oct 31. pii: S0022-5347(15)05163-0. doi: 10.1016/j.juro.2015.10.140. [Epub ahead of print]