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Immediate re-biopsy and transition zone biopsy during active surveillance
With the implementation of PSA as a screening tool during the past three decades, an increasing number of low-risk and very low-risk prostate cancers are being detected. Given the low risk of progression and limited benefit of radical treatment, active surveillance of low-risk prostate cancers is becoming increasingly popular as patients and physicians try to avoid over treatment and exposure to possible adverse events that radical surgery or radiotherapy may have. Certainly, not every patient is a candidate for active surveillance, and multiple variables have to be taken into account when considering a patient suitable (i.e. Gleason grade, number of biopsy cores involved with cancer, percent cancer per core). Efforts have been made to better identify patients who are ideal candidates. However, about 30% of patients started on active surveillance show progression of disease on a follow-up biopsy at one year or fail active surveillance altogether and ultimately undergo treatment (Godtman et al., European Urology, 2013). It is unclear whether the disease in these patients really progresses and shows more adverse features at a later time, or whether these features might have been discoverable early on already, but were missed on initial biopsy. Interestingly, in prostatectomy cohorts, upstaging and upgrading from initial biopsy to prostatectomy specimen have been shown to be equally as high (40%), especially in low-risk cancers (Fleshner et al., Urology, 1998). These two observations lead to the question of whether patients on active surveillance may be inadequately sampled during their initial transrectal prostate biopsy, upon entering an active surveillance protocol.
In an attempt to better define patients who exhibit histopathologic features on prostate biopsy that are in concordance with active surveillance protocols (such as low- or very low-risk prostate cancer), two studies from the Department of Urology at Columbia University Medical Center (CUMC), were recently published: The first one, from Motamedinia et al. in the November 2013 issue of Urology, studied retrospectively the usefulness of a repeat biopsy in 60 patients upon election to undergo active surveillance. Most of these patients (70%) had been referred to CUMC as a tertiary referral center with an established diagnosis of prostate cancer on an initial prostate biopsy, while the remaining 30% had been initially biopsied at CUMC itself. Average time from initial to repeat biopsy was two months. Overall, the total numbers of biopsy cores taken on repeat biopsy in this analysis was on average 6.2 cores greater per patient (with a mean of 17 vs. 13.5 cores). Strikingly, more than 31% of patients showed features on the repeat biopsy that made them incompatible with active surveillance and were referred to definitive treatment. This number of patients equals the number of patients that is thought to show progressive features on follow-up biopsy at the 12-month time point during active surveillance as mentioned above, but it seems more likely that those 30% that are thought to have progressive disease on follow-up biopsy at one year were actually under-sampled and inadequately staged upon entering the active surveillance protocol. The retrospective nature of this analysis may limit the interpretation, especially as patients were not randomized for either immediate re-biopsy or no immediate re-biopsy. The main reason to perform a re-biopsy in this cohort was that the number of cores taken upon initial biopsy was considered too few. However, this data may be extrapolated to larger cohorts, encouraging clinical practitioners to perform an immediate repeat biopsy, especially if the number of biopsy cores taken initially is considered inadequate. Consequently the failure rate of patients initially started on active surveillance, risk of significant progression during surveillance, and risk of patients developing non-localized disease not amenable to curative localized treatment options would decrease.
The second publication by Richard et al., published in the Journal of Urology studied the use of biopsies of the transition zone on follow-up biopsies in patients on active surveillance. Although most of the prostate carcinomas arise in the prostatic periphery, about 10% originate in the transition zone. The analysis by Richard et al. showed that including the transition zone on follow-up biopsy only extremely rarely helps detect patients who exhibit features that are consistent with more aggressive and progressive disease. As transition zone biopsies may pose an increased risk of infection and bleeding to the patient, they should be reserved for those patients who had prostate cancer initially, exclusively, in this area of the prostate.
With prostate cancer being the most common cancer in men, effective treatment options are available. However, prostate cancer grows slowly and not every patient requires immediate radical treatment. Patients with low-grade diseases may therefore rather be monitored closely, to delay or avoid therapies that may pose significant side effects for the patient (i.e. urinary incontinence, erectile dysfunction). Active surveillance does not mean to not ever treat the cancer, through close monitoring of the cancer, quality of life could be maintained without risking significant progression of the cancer, and without jeopardizing the curability of the cancer at a later time point. Therefore active surveillance has evolved as another mainstay to monitor and approach low-risk prostate cancer, and the researchers in the Department of Urology at Columbia University Medical Center have shown in their two studies how prostate biopsies can be performed and optimized to improve monitoring of the disease, while reducing the risks and side effects of prostate biopsies, and improving the accuracy of initial assessment of the eligibility of patients for active surveillance.
Written by:
Sven Wenske, MD as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
Department of Urology
Columbia University Medical Center
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