He began by highlighting two factors which underpin the importance of this topic. First, there is an increasing proportion and absolute number of patients being diagnosed with high-grade and metastatic prostate cancer, as Dr. Hu and colleagues have shown.
Second, over the past few years there has been increasingly mounting evidence that advances in imaging, particularly, with magnetic resonance imaging have fundamentally changed the nature of prostate cancer detection and risk stratification. He highlighted the PRECISION trial, in particular, and noted that it showed that use of mpMRI in the pre-biopsy space decreased detection of low-grade cancers while increasing detection of clinically significant disease.
He then posed two key questions. First, what approaches are best for identifying these men? And, second, are there advances in imaging or surgical approaches which would improve outcomes for these men?
Addressing the first question, Dr. Schaeffer highlighted the NCCN risk stratification and pointed out the significant heterogeneity among patients with “high-risk” disease. He then highlighted work he had done with Drs. Sundi and Ross to delineate a subset of very-high risk patients, a substratification which has been incorporated in the NCCN risk groups, along with substratification of intermediate risk disease to include “unfavorable” intermediate risk.
After pointing out that nomograms are cost efficacious and cost-effective at predicting final pathological stage, he noted that they were limited by their lack of anatomic information. He then highlighted the potential benefit of mpMRI.
First, mpMRI may assist with local staging. He discussed a recently published diagnostic meta-analysis which demonstrated that mpMRI had excellent specificity for SVI and ECE. However, in men with high-risk disease for whom there is a high index of suspicious, sensitivity is perhaps more important than specificity. In single institutional series, mpMRI fared somewhat worse in this setting with an NPV of 58% and PPV of 89% for EPE.
Dr. Schaeffer then discussed a randomized controlled trial from Oslo which assessed whether used of mpMRI prior to prostatectomy influenced rates of positive surgical margins. While there was a numeric benefit, this failed to reach statistical significance.
Instead, he suggested that real-time, intra-operative approaches could provide more valuable information to guide surgery. Such an approach is the Neurosafe technique developed at the Martini Clinic. This involves real-time, pathologic assessment of the tissue around the neurovascular bundle and has been shown to improve both rates of positive surgical margins and functional outcomes.
Next, he addressed the question of whether imaging could improve loco-regional staging. Current, conventional imaging approaches including computed tomography and technetium bone scan have poor sensitivity and specificity. Unfortunately, mpMRI appears to be similarly poor for regional staging with a 55% sensitivity for the identification of lymphadenopathy. Thus, many investigators have examined the use of PET scan in this setting. In addition to numerous FDA-approved tracers, PSMA based radiotracers appear to hold great promise. While the specificity of PSMA PET-CT is high, there remains an issue with the sensitivity of detecting small positive lymph nodes. Thus, Dr. Schaeffer is undertaking a trial of PSMA PET-MR.
Dr. Schaeffer advocated that increased use of advanced imaging is likely to result in an increased extent of lymphadenectomy in these patients. He highlighted observational data that demonstrates that an increased nodal yield confers a survival benefit in patients with both pN0 and pN1 disease.
Taken together, he advocated use of mpMRI prior to all prostate biopsies and use of a Gel-port to facilitate real-time pathologic assessment in high-risk patients.
Presented by: Edward Schaeffer, MD, PhD, Northwestern University
Written by: Christopher J.D. Wallis, Urology Resident, University of Toronto @WallisCJD at the American Urological Association's 2019 Annual Meeting (AUA 2019), May 3 – 6, 2019 in Chicago, Illinois