Identifying Suitable Candidates for Active Surveillance in Prostate Cancer

This review is designed for physicians and patients who have access to multiparametric MRI technology available in several major health research institutions.

A recent article by Drs. Peter Choyke and Stacy Loeb  (from the National Cancer Institute, NIH) in the journal Oncology and e mailed through the CancerNetwork provided a important summary of active surveillance, a safe, appealing approach that spares radical treatment and does not increase disease-specific mortality. However, the authors conclude that current methods of identifying low-risk patients are flawed and cannot always accurately predict candidates for active surveillance. In the article, the authors focus on the role of active surveillance for patients with low-risk disease and how multiparametric MRI (mpMRI) can impact decision making for entering and monitoring patients on active surveillance. The article is written mainly for physicians and should be discussed with them if you are considering active surveillance as an option.

The active surveillance decision-making process begins with a prostate biopsy, for which there are two main triggers: elevated PSA and/or a palpable lesion on digital rectal examination. The current standard of care is to obtain a 12-core biopsy under transrectal ultrasound (TRUS) guidance, in which two samples are obtained from the apex, the middle, and the base of the prostate on two sides (six samples per side). Each sample is interpreted by a pathologist using the Gleason scoring system ranging from 3+3 to 5+5. Patients who harbor low-volume 3+3 tumors or 3+4 tumors with only a small percentage of grade 4 are eligible for active surveillance. The use of active surveillance in the United States has increased in recent years, with over 40% of low-risk tumors managed in this manner, and even higher rates for men over 75 years of age. Active surveillance is different from watchful waiting, which is usually reserved for elderly men with reduced life expectancy. In watchful waiting, the physician will not perform serial tests such as biopsies because there is no curative intent, so treatment is only given for symptomatic progression. In contrast, active surveillance infers that the patient is followed with a schedule of serial PSA tests and biopsies, with the latter meant to detect patients who convert from a low-grade to an intermediate- or high-grade tumor over time.

Implementing active surveillance varies with the medical  institution and presents its own problems. At this point, for this discussion, I would refer you the reader to the linked section entitled “Implementing Active Surveillance”.

The next section discussed the role of mpMRI in identifying active surveillance candidates. mpMRI can identify lesions missed by the standard TRUS biopsy or can more properly characterize cancers detected at TRUS biopsy. “Because a standard TRUS-guided biopsy predominantly samples the posterior peripheral zone, the rest of the gland is undersampled. Moreover, since TRUS-guided biopsies are really blind samples of the prostate, tumors in the posterior peripheral zone may be incompletely sampled or their size greatly underestimated. Therefore, before placing a patient on active surveillance, we perform an MRI to identify any lesions that were potentially missed or undersampled. In the case of active surveillance candidates, approximately 20% to 30% of patients who were initially considered good candidates for active surveillance are directed toward active treatments such as surgery or radiation as a consequence of finding additional lesions or resampling known lesions with MRI guidance. For patients in whom the MRI is negative or reveals nothing more than was discovered by TRUS biopsy, active surveillance is an excellent choice. Thus, an initial MRI followed by MRI-TRUS–guided biopsy has become routine in our institutions to identify patients who are ideal candidates for active surveillance. This provides greater assurance to the clinician and patient that the proper management has been selected.”

“It would seem logical that MRI could also be used in place of repeat biopsies to monitor patients who are on active surveillance. Although this is a very attractive possibility for patients due to the risk and burden associated with multiple biopsies over time, good long-term data are not yet available to support this policy. In our own institutions, MRI is commonly performed on a routine basis (annually in the case of the National Cancer Institute), and changes in the appearance of the MRI can trigger a repeat targeted biopsy.” …..” In our own experience, the vast majority of active surveillance patients who have an initial qualifying MRI and MRI-TRUS biopsy exhibit minimal or no change in their MRI over many years, making this approach quite promising.”

A variety of other commercially available serum, urine, and tissue biomarkers have been introduced to help clinicians decide whether to initiate and maintain a patient on active surveillance. Their value relative to MRI has not been tested adequately to draw conclusions as to whether these can be used in place of MRI or as an adjunct to MRI. One of these serum markers is the Prostate Health Index, which combines total, free, and proPSA using a mathematical formula. This test was previously shown to predict changes on biopsy in men on active surveillance, and in the future might be used to monitor patients in conjunction with mpMRI.  Several genomic tissue tests including Prolaris, Oncotype DX, and Decipher are also commercially available to help determine aggressiveness beyond the information provided by Gleason score. These may be used to help assess eligibility for active surveillance in borderline cases such as high-volume Gleason 6 or low-volume Gleason 3+4; however, there are no published data on their utility for monitoring during surveillance, and they require tissue from a biopsy.”

The authors conclude that “active surveillance is an excellent alternative to surgery or radiation in patients with low-risk cancers. However, the current methods of ascertaining whether a patient harbors a low-risk cancer are flawed, and data obtained by PSA or traditional TRUS biopsy do not accurately predict good candidates for active surveillance. MRI- and MRI-TRUS–guided biopsies of the prostate appear to assist in the decision to place a patient on active surveillance by detecting lesions outside the normal biopsy template or by providing more information about a lesion within the potentially undersampled template. Less certain is the role of MRI in delaying or eliminating subsequent biopsies, although it is increasingly being used in this manner, since repeat prostate biopsies are a source of patient noncompliance. The role of other new biomarkers in the decision-making process and their utility compared with MRI remains to be determined. What is most encouraging is that more men can now safely and confidently delay or avoid unnecessary radical surgery for low-risk prostate cancers and retain a high quality of life even with a prostate cancer diagnosis.” The full article can be accessed in this link.

 

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