By: Dan Sperling, MD

The clinical prostate cancer (PCa) world of is trending toward increasing use of active surveillance (AS) as a strategy for avoiding overtreatment of low-to-intermediate risk disease.[i] At the same time, a great deal of professional dialogue involves establishing universal criteria to qualify patients for AS. In addition to being psychologically qualified (comfort level for living with untreated PCa, importance of near-term quality of life, concern about side effects of whole-gland treatment) the standards developed by the Brady Urological Institute of Johns Hopkins are widely used. These include:

1. For very low risk patients with PSA <10 – Gleason <7, stage T1c, PSA density <0.15, and PCa on only one side of the gland with <3 cores positive for cancer regardless of percent core involvement
2. For very low risk patient with PSA 10-20 – Gleason <7, stage T1c, PSA density <0.10, and PCA on only one side of the gland with <3 cores positive for cancer regardless of percent core involvement
3. For low risk patients >65 years old – Stage T1c or T2a, Gleason score <7, PSA <10. If life expectancy is less than 10 years, AS is the preferred management choice.
4. For intermediate risk patients – Stage T2 or PSA 10-20 or Gleason 3+4, and life expectancy is less than 10 years.[ii]

Conventional transrectal ultrasound guided (TRUS) needle biopsy results in up to 40% false negative results (PCa missed by the biopsy needles) and/or undergrading (failure to sample the most aggressive area of a tumor). It would be unfortunate for a PCa patient to undertake AS if in fact his prostate harbored disease of greater volume or aggressiveness than what his TRUS biopsy found. The visual information obtained through multiparametric MRI (mpMRI) has demonstrated that AS can be ruled in or out based on imaging in addition to TRUS biopsy (see https://sperlingprostatecenter.com/mri-reclassification-of-prostate-cancer-for-active-surveillance/ for more information). Even more compelling, mpMRI-targeted biopsies continually demonstrate greater ability to qualify men accurately for AS, and may be able to replace TRUS biopsy altogether.

A Belgian study published in April, 2015[iii] reported better detection than TRUS biopsy of significant PCa, a clinical factor that may contraindicate AS. One hundred twenty-nine men with no prior biopsy underwent mpMRI scans followed by standard TRUS biopsy. In addition, if the imaging showed suspicious lesions, they underwent mpMRI-guided biopsy targeted to the regions of interest. The detection rates of TRUS vs. MRI targeted biopsy were then analyzed and compared. Not surprisingly, the targeted method resulted in a higher detection rate of clinically significant cancer. Comparing the proportions of needle cores that were positive to significant PCa revealed 28.9% positive for MRI targeting vs. 9.8% for TRUS, and the proportion of men with Gleason score > 7 was higher with MRI targeting. These findings imply that many patients choosing AS on the basis of TRUS biopsy alone are missing crucial information about their PCa. Another advantage of the targeted biopsy is the use of fewer needles that still produce a more accurate diagnosis.

To test the use of MRI-targeted biopsy for clarifying true candidacy for AS, a French research team investigated whether it would alter the choices of patients already set for AS based on TRUS biopsy.[iv] They enrolled 281 men with elevated PSA whose TRUS biopsy results placed them within their own criteria for AS: PSA < 10 ng/ml, no Gleason grade 4/5,<  5 mm involvement of any biopsy core, and ? 2 positive TRUS needle cores. All of the men already had mpMRI scans done before their TRUS biopsy; if they were found to have suspicious lesions, they had an additional MRI-guided targeted biopsy (2 needle samples from each region of interest) during their TRUS biopsy session. 58% of the men (163) had suspicious areas on MRI, and the targeted biopsies were positive in 50% of them (81 out of the 163). The authors reported, “Overall, 10% (28/281) patients were reclassified by MRI-TB as not eligible for AS based on Gleason score (8), on cancer length (20) or both (9). Suspicious areas on MRI were located in the anterior part of the prostate in 54%(15/28).” Two additional factors that correlated with reclassification to a higher risk group were older age, and smaller prostate volume. The team concluded that integrating mpMRI-targeted biopsies into the process of qualifying patients for AS could reduce the risk of reclassification into higher risk groups at a later date when the cancer might have progressed to the point where a treatment window had been missed.

With today’s pattern of increasing AS recommendations, doctors and patients must have access to the most accurate and comprehensive diagnosis. By converting from systematic TRUS biopsies to MRI-guided targeted biopsies, better knowledge about the size, location, extent and aggression level of a tumor becomes available. As an added safeguard, it may be desirable to submit tissue from the needle samples for genomic analysis as a safeguard against missing the minority of cell lines that have the potential to become lethal.

Patients who choose AS deserve to gain the full benefit of delaying overtreatment without putting their lives on the line. MRI-guided targeted biopsies may be the best way to achieve that.

[i] Cooperberg MR1, Carroll PR1. Trends in management for patients with localized prostate cancer, 1990-2013. JAMA. 2015 Jul 7;314(1):80-2. doi: 10.1001/jama.2015.6036.

[ii] http://www.urology.jhu.edu/prostate/active_surveillance_selection.php

[iii] Peltier A, Aoun F, Lemort M et al. MRI-targeted biopsies versus systematic transrectal ultrasound guided biopsies for the diagnosis of localized prostate cancer in biopsy naïve men. Biomed Res Int. 2015;2015:571708. doi: 10.1155/2015/571708

[iv] Ouzzane A, Renard-Penna R, Marliere F et al. MRI-targeted biopsy improves selection of patients considered for active surveillance for clinically low-risk prostate cancer based on systematic biopsies. J Urol. 2015 Mar 4. pii: S0022-5347(15)03265-6. doi: 10.1016/j.juro.2015.02.2938