Clinical Challenges: Can MRI and Biomarkers Replace Biopsy for AS in Prostate Cancer?

Can active prostate cancer surveillance be conducted without biopsies?

While patients under active surveillance undergo periodic prostate specific antigen (PSA) and tumor burden evaluations, which typically involve periodic prostate biopsies, “these are increasingly augmented and, in some very careful circumstances, replaced by resonance studies. magnetic and / or biomarkers, “said Matthew Cooperberg, MD, MPH, of the Helen Diller Family Comprehensive Cancer Center at the University of California San Francisco (UCSF). “I say very carefully because there are concerns that biopsies are being replaced by MRIs and biomarkers too frequently, and perhaps in advance of the tests.”

“The guidelines clearly state that active surveillance is based on PSA and tumor biopsy,” Cooperberg said. MedPage today. “There are parts of the world, the UK for example, where they believe that MRI is an adequate substitute for prostate biopsy. I and many others do not think MRI in 2020, based on the current PI-RADS system, is nowhere near ready to replace biopsies on a routine basis. Accuracy is not available using the PI-RADS system and the false negative rate for high-grade disease – nearly 25% – is too high. Not a replacement. “

According to an article in The Journal of Urology, recent data from the Canary Prostate Cancer Active Surveillance (PASS) multicenter cohort indicate that systematic biopsy should be performed on patients with negative MRI and included in the management of patients with positive MRI.

This study, led by Michael Liss of the University of Texas Health Science Center at San Antonio, included 361 patients undergoing 395 prostate MRI scans with a median follow-up of 4.1 years (IQR 2.0–7.6). MRI led to reclassification in 27% of cases. The positive predictive value for GG ≥2 cancer detection was 31% (95% CI 26% -37%), while the negative predictive value was 83% (95% CI 76% -90%) “, suggesting that a Negative MRI will still miss a substantial percentage of patients with ≥2 “GG disease.

“Additionally, systematic biopsies detected a similar number of GG≥2 unique tumors as MRI-targeted nuclei,” Liss and her colleagues wrote. “Therefore, if the goal of surveillance biopsy is to identify higher-grade disease, both systematic and targeted biopsies should be obtained for men with a region of interest identified on MRI.”

They also found that while PI-RADS 5 lesions were significantly associated with updating or reclassification compared to PI-RADS 1 and 2, the models that included PI-RADS scores improved only minimally compared to models that only contain clinical variables.

According to another recent study, published in European urology, multiparameter magnetic resonance imaging (MP) can improve the detection of clinically significant prostate cancer, but alone cannot replace confirmatory or surveillance biopsies.

The study, led by Carissa Chu, MD, of UCSF and co-author of Cooperberg, included 344 men under active surveillance who had at least one mpMRI scan and one biopsy after cancer diagnosis. Men had 408 mpMRI scans during a median of 71 months under active surveillance. The median time between prostate biopsies was 16.5 months.

The overall negative predictive value for mpMRI was 79.5% and ranged from 74.4% to 84.6% for all active surveillance biopsies up to the fourth surveillance biopsy. In men with PSA density ≥0.15 ng / mL / cm3, the overall negative predictive value for mpMRI was 65.5% and ranged from 57.1% to 73.3% in serial mpMRI scans.

“These results support the hypothesis that mpMRI is useful but insufficient for ruling out pathological reclassification, especially at confirmatory biopsy or in the presence of other risk factors,” wrote Chu and his colleagues.

“We are very interested in adapting the intensity of the surveillance protocol,” Cooperberg stressed. “Biopsies are uncomfortable, they have risks of infection and there are costs associated with them. And patients certainly don’t want to sign up for 20 biopsies in 20 years.”

Cooperberg and colleagues recently identified several clinical parameters that can predict disease progression and can be used to identify patients on active surveillance who may be followed less intensively. These include the maximum percentage of positive nuclei, history of any negative biopsy after diagnosis, time since diagnosis, body mass index, prostate size, prostate specific antigen at diagnosis, and antigen kinetics prostatic specific.

The team determined that a prediction model based on these parameters, and tested on 850 men in the PASS cohort, could potentially be a less invasive way to assess disease change and thus avoid multiple biopsies.

Regarding the role biomarkers should play in active surveillance protocols, Cooperberg said that tests such as Decipher, Prolaris or Oncotype DX Prostate can provide important prognostic information.

Earlier this year, the American Society of Clinical Oncology released guidelines for prostate cancer biomarkers in which a panel of experts recommended that proprietary tests be offered in situations where the test result, when considered together with routine clinical factors, it can influence management. However, they did not recommend routine sorting of molecular biomarkers.

The Panel came to a similar conclusion for the use of MRI and genomics in newly diagnosed men with cancer eligible for active surveillance: “only in situations where the outcome, when considered with routine clinical factors, is likely to affect management “, such assessments are clearly useful.

“If a biomarker test is high, it will usually prompt us to do a more aggressive re-biopsy program,” Cooperberg said. “Can we tell a patient now, ‘Your biomarker tests were low, so you can now postpone the interval to your next biopsy for a longer period of time’? This makes clinical sense, but the data really don’t exist to support it. , yet. “

As for definitive biopsy replacement, Cooperberg suggested that with better studies and long-term follow-up, doctors can likely think of ways to use MRI and biomarkers to increase biopsy intervals.

“But, we haven’t gotten to replace the biopsy all together yet,” Cooperberg said. “We need next-generation imaging or we need better studies of existing biomarkers to get around concerns about tumor heterogeneity and other factors that only reduce confidence in the current generation of markers. In the end, the Holy Grail is having a liquid test that will be less expensive and avoid heterogeneity problems. But we are still years away from that degree of evidence “.