The 2020 SUO meeting presented multiple important updates in prostate and bladder cancers. As one of the meeting organizers, I was overwhelmed by the breadth and depth of the program. The organizing committee consisted of key experts including my partners at Northwestern, Drs Ashley Ross and Josh Meeks. The only regret I had was the fact the meeting was virtual and I could not directly interact with my friends and colleagues! Next year! Here are some highlights of the meeting.
In regards to prostate cancer screening, results of the relatively uncontaminated well-designed European trials demonstrated that systematic prostate cancer screening with PSA reduces prostate cancer specific mortality albeit with the allowance for over diagnosis of clinically insignificant prostate cancer that may lead to overtreatment. Multiple strategies have been put forth, both utilizing existing tools and more recently developed tools to refine prostate cancer screening. In the EAU/SUO lecture, Dr. Albers summarized strategies currently being tested in large prospective randomized trials and discussed first reports from German PROBASE trial for risk-adapted prostate cancer early detection based on baseline PSA values in young men. Initial results from PROBASE confirm the very low prevalence of prostate cancer (and particularly intermediate or high grade disease) in men under 50, the ineffectiveness of DRE in prostate cancer screening, and the ability to have roughly 90% of young men avoid repeat screening until age 50. While this trial sets a biopsy metric based on a PSA threshold, he highlighted other prospective trials such as ProScreen which compares no prostate cancer screening to prostate cancer screening with 4K score and MRI and evaluates PCSM at 10, 15 years. He also discussed ongoing efforts to evaluate bi-parametric MRI in prostate cancer screening. Dr. Eric Klein, who received the Richard D. Williams Prostate Cancer Research Excellence Award, furthered the discussion of emerging approaches to screen for clinically significant prostate cancer by reviewing data from the newly developed IsoPSA test.
Once the suspicion for prostate cancer becomes great enough, diagnosis is confirmed by prostate biopsy. Previous standards have utilized systematic peripheral zone sampling with transrectal ultrasound guidance. With improvements in detection of localized prostate cancer through mpMRI this standard has changed and use of mpMRI prior to biopsy can increase the detection of clinically significant prostate cancer. Dr. Peter Pinto demonstrated this point but also stressed limitations in mpMRI sensitivity are such that systematic sampling cannot be abandoned, particularly in men considering active surveillance. Moreover, utilization of MRI-targeted and systematic biopsies together should increase our confidence in placing men on surveillance as upgrading rates at prostatectomy can be reduced to below 15% if this technique is utilized. Along with efforts to make prostate biopsy more accurate have come efforts to decrease its morbidity both at the individual and population level. Dr. Jim Hu reviewed this and discussed in-office perineal biopsies which require no antibiotic prophylaxis and can better sample the anterior prostate. Dr. Hu and myself have an ongoing NCI-sponsored trial to investigate cancer detection and side effects between these two approaches.
Dr. Declan Murphy reviewed results of the multi-center ProPSMA trial which demonstrated that PET-PSMA for the staging of men with unfavorable intermediate or high-risk prostate cancer is roughly 30% more accurate than conventional imaging with higher management impact, less equivocal studies, and less radiation given to patients. Dr. Cooperberg discussed some of the limitations to PET-PSMA imaging and brought up important considerations, particularly as some PET-PSMA compounds have started to be approved in the U.S.
In advanced disease, the importance of precision medicine in prostate cancer was stressed. Dr. Kara Maxwell highlighted data from the SU2C efforts showing that more than 20% of men with mCRPC will have DNA damage repair machinery mutations and a larger number will have various actionable mutations. She highlighted the importance of broad molecular testing particularly in light of recent tumor agnostic approvals of immunotherapy and NTRK inhibitors. Dr. Hussain took this discussion further by thoroughly reviewing the newly approved PARP inhibitors in mCRPC which improved progression-free survival and overall survival. Dr. Spratt highlighted that as the FDA has allowed for a permissive approval of Olaparib in not just BRCA-mutated patients where it showed the most effect, but in all patients with DNA damage repair mutations covered in cohort A and B of the study (with exclusion of PPP2R2A), the onus is on us as clinicians to make careful choices regarding drug sequencing and utilization. While seeing the approval of targeted therapies in prostate cancer is exciting, data was presented re-affirming the androgen addiction of prostate cancer and the benefit of targeting the androgen signaling cascade. Dr. Sternberg reviewed the overall survival benefit of next generation androgen receptor blockers such as enzalutamide in the nmCRPC showing a 30% survival benefit for intensification of androgen blockade in these men (similar benefits are suggested by trials with apalutamide and darolutamide). Finally, consideration was given to oral androgen deprivation therapy through the LHRH antagonist Relugolix. Dr. Shore reviewed the HERO trial, showing Relugolix to be an effective castration agent with less cardiovascular toxicity, particularly in men with history of previous major cardiovascular events. Dr. Ashley Ross then commented on issues that may need to be addressed before Relugolix is widely adopted across clinical settings, including its efficacy and dosing regimen when combined with radiation therapy for localized disease, and its behavior as part of combinatorial systemic regimens for metastatic prostate cancer.
Within Bladder cancer, there were several key presentations. Surena Matin, MD (MD Anderson Cancer Center) described the long-term durability of UroGen’s mitomycin chemoablative hydrogel (UGN101) from the single-arm Phase III OLYMPUS trial. Initially published in Lancet Oncology, the authors described their 71-patient trial with high-volume, low-grade, upper-tract urothelial cancer with a 59% (42/71) complete response at 4–6 weeks after the initial 6-week administration. During the SUO, they described at 12 months, 81% maintained their response and 23/41 (56%) maintained their complete response. Dr. Matin noted the use of maintenance therapy was highly variable and more treatments were associated with higher ureteral stricture rate (43% overall) and occurred over a median of six instillations. While not fully described, there is some hope this may decrease with antegrade administration of UGN101. There is significant enthusiasm that we will soon have better approaches for upper tract tumors, using targeted therapies and innovative technologies, like UGN101.
Overall, there were many spectacular presentations at this year’s SUO meeting. In spite of the pandemic, the field of Urologic Oncology continues to make substantial progress toward cures in all of our disease spaces.
Image: magic mine / shutterstock
