Peter R. Carroll, MD, MPH

Peter R. Carroll, MD, MPH

University of California, San Francisco

San Francisco, California

Dr. Peter Carroll holds the Ken and Donna Derr-Chevron Professorship in Prostate Cancer and the Taube Family Distinguished Professorship in Urology at the University of California, San Francisco (UCSF). He is also the Associate Director of Strategic Planning and Clinical Services and Program Leader of the Prostate Cancer Program at the Helen Diller Family Comprehensive Cancer Center at UCSF. Dr. Carroll graduated with honors from Georgetown University School of Medicine. He then went on to complete general surgery training and a urology residency at UCSF, as well as a Fellowship in Urologic Oncology at Memorial Sloan Kettering Cancer Center in New York City. He has taught at the UCSF Department of Urology since 1986, and he became the department chair in 1996. Under his leadership, the department has been consistently ranked one of the top urology departments in the country by U.S. News and World Report. The department has grown, serving an increasingly larger patient population, expanding its research programs, and attracting future leaders in the field for training. Under Dr. Carroll’s leadership, the department managed an average of over $10 million in research grants that put UCSF in first place for urology funding for five consecutive years. Dr. Carroll also established the UCSF Department of Urology’s Tissue Core, a biobank of blood, urine, and residual prostate, bladder, and renal tissues for more than 6,000 consenting patients. In addition to his many accomplishments at UCSF, Dr. Carroll has authored or co-authored over 650 publications, is an active member of numerous professional medical societies, and is currently principal or co-investigator on numerous scientific studies. He is also Past-President of the American Board of Urology (2006-2008). His drive to perfect nerve-sparing prostatectomy has led to many technical innovations, and his pioneering efforts in standardizing an active surveillance regimen has led to many patients postponing radical treatment while maintaining a low risk of cancer progression.

Disclosures:

Articles by Peter R. Carroll, MD, MPH

Use of Polygenic Risk Scores for Prostate Cancer Screening

Peter R. Carroll, MD, MPH, Professor of Prostate Cancer and Urology at the University of California, San Francisco, introduces his talk on polygenic risk scores by asserting that serum prostate-specific antigen (PSA) testing has limitations as a stand-alone screening tool. He explains that hereditary factors have a strong influence on prostate cancer risk and outcomes and that prostate cancer has high heritability. Dr. Carroll argues that while high-penetrance genes are important, they only explain a fraction of prostate cancer risk. Further, numerous genome-wide association studies (GWAS) have identified over 250 single nucleotide polymorphisms (SNPs) associated with risk. Dr. Carroll lays out the potential relevance of polygenic risk scores, showing where the scores have the potential to impact clinical care by supporting risk prediction, diagnosis, treatment decision-making, and prognosis of disease course and outcome. He then reviews a trans-ancestry genome-wide association meta-analysis of prostate cancer that demonstrates that genomic risk score (GRS) was predictive across populations. The study concluded that 269 risk variants were estimated to capture 33.6 percent of familial relative risk (FRR) in men of East Asian ancestry, 38.5 percent in Hispanic men, 42.6 percent in men of European ancestry, and 43.2 percent in men of African ancestry, with higher GRS associated with younger age at diagnosis and family history, but not disease aggressiveness. Dr. Carroll concludes with a summary of the use of GRS in prostate cancer early detection: prostate cancer is related to many risk variants across populations; GRS improves on the use of age and family history in assessing risk, though early detection guidelines have not incorporated GRS use yet; and larger populations (particularly those of African ancestry) require further examination. 

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Prostate Cancer Early Detection 2021

Peter R. Carroll, MD, MPH, Professor of Prostate Cancer and Urology at the University of California, San Francisco, examines data from randomized controlled trials that studied prostate-specific antigen (PSA) testing and mortality. He emphasizes that data show that the number of patients screened and diagnosed to avoid one death improves significantly over time and thus it is important to recognize the long-term impact of screening. Dr. Carroll briefly discusses American Urological Association (AUA), U.S. Preventive Services Task Force (USPSTF), American Cancer Society (ACS), and National Comprehensive Cancer Network (NCCN) recommendations, noting that some recommendations are vague with regard to biopsy. Dr. Carroll then displays a pictogram of what he calls “the Achilles heel of PSA screening.” It shows that among 1,000 men in the US, about 250 have an elevated PSA. If all patients with elevated PSA are biopsied, the results show that half have no disease and, of the remaining men, about 30-40 percent have low-risk disease. He cites harmful effects of overtreatment, mentioning sepsis as an example, but concludes that the harms outweigh the benefits in this screening paradigm. Dr. Carroll then explains that detection paradigms have changed from a “detect all, treat all” approach to a “detect some, treat some” approach, utilizing surveillance for patients with lower-risk disease. Dr. Carroll outlines NCCN Guidelines for 2021, which include a continuation of support for early detection efforts; baseline testing at age 45; germline testing; an acknowledgment that optimal screening of high-risk patients (e.g., African-American men) is not completely known; provisions for alternatives to routine biopsy; and a recognition of the value of active surveillance for low-risk cancers. He highlights the recommendation that digital rectal examination (DRE) should be used as a complement to PSA testing, not as a standalone screening test. Dr. Carroll concludes that DRE could not be implemented effectively in a nationwide screening program. Dr. Carroll explains that, increasingly, doctors are opting for tests of specificity (biomarker or MRI) before opting for biopsies. He asserts the value of using MRI before biopsy, since MRI targeting increases the detection of high-grade cancers while limiting the detection of low-grade cancers. However, he explains that a decision not to biopsy requires use of a biomarker test along with MRI, since the negative predictive value (NPV) of MRI is 85 percent. He cites the PROMIS trial and asserts that a negative MRI alone is insufficient. Dr. Carroll then cites data from a recent trial in the NEJM showing that MRI-targeted biopsy decreases the likelihood of negative or benign biopsy and testing with biomarkers can reduce biopsies by 20-65 percent while missing few (2.5-8 percent) high-grade cancers. He asserts that recent studies suggest that upfront biomarker testing with conditional MRI may be the most efficient strategy for early detection, with cost and availability being strong considerations. He supports this assertion with data on various biomarker tests as well as early detection algorithms. Dr. Carroll returns to the NCCN recommendations on management of biopsy results before concluding his discussion, reemphasizing that prostate cancer early detection in well-informed, healthy men saves lives.

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PSMA PET Imaging at Time of Diagnosis

Peter R. Carroll, MD, MPH, Professor of Prostate Cancer and Urology at the University of California, San Francisco, discusses PSMA PET imaging and compares it to conventional imaging at the time of diagnosis. He states that conventional imaging has insufficient sensitivity when staging men with high-risk localized prostate cancer at the time of diagnosis, therefore providing the rationale for using PSMA PET. Dr. Carroll then summarizes data demonstrating PSMA PET’s sensitivity. He begins with the OSPREY trial, which shows overall pelvic lymph node sensitivity of 40.3% and specificity of 97.9% for 18F-DCFPyL PSMA PET, and then looks at a meta-analysis of Gallium-68 PSMA-11 PET that found a sensitivity of 74% and specificity of 96%. He also cites a multicenter, two-arm, randomized study in Australia as proof of PSMA PET’s superiority to conventional imaging due to evidence of lower radiation exposure and higher specificity. Dr. Carroll discusses how PSMA PET impacts treatment planning, looking at a study on the impact of staging PSMA PET scans on radiation treatment plans that found major changes in 30% of patients and minor changes in 13-15%. He believes that the field is moving towards intraoperative imaging and outlines a study he is currently working on that is using an advanced firefly camera for intraoperative imaging and testing to see if the process will result in more therapeutic interventions. Dr. Carroll states that so far the study has been able to identify tumor fluorescence of all patients, has been very effective at identifying residual disease at surgical margins, and has had only one adverse effect: transitory green urine. He concludes that PSMA PET imaging is more sensitive than standard imaging and will soon replace conventional methods, although the impact on long-term outcomes remains to be determined.

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Management of Biochemical Recurrence

Peter R. Carroll, MD, MPH, Professor of Prostate Cancer and Urology at the University of California, San Francisco, discusses advancements in knowledge of biochemical recurrence post radical prostatectomy. He begins with an overview of the evolution of radical prostatectomy (RP), highlighting that it has become a treatment option designated for high-risk patients, more multimodal, and more enhanced by biomarker and imaging technology. Dr. Carroll shows data from the CAPTURE trial suggesting that when looking at 18-year cause-specific mortality, RP has a benefit to high risk patients over low risk patients. He reviews data from a Martini-Klinik trial on PSA after RP predicting cancer death that found 75.5% survival in RP patients with detectable PSA vs 96.2% in patients with undetectable PSA. Dr. Carroll also discusses data from a trial he took part in managing which supports the data from Martini-Klinik. He then overviews data from the RAVES, GETUG – AFU 17, and RADICALS RT trials that all compare salvage therapy against adjuvant and found no real difference in outcomes with differences of 3% at most. Dr. Carroll reviews data showing that early adjuvant therapy has a survival benefit for high-risk patients with Gleason scores of 8-10 and UCSF data showing 33% salvage PSA recurrence-free survival post salvage radiation at 10 years. He discusses how empirically based treatment strategies don’t take into account the treatment niches shown by the data he has reviewed and recommends that exact treatment strategies are utilized on a patient by patient basis and that a measured approach to managing biochemical recurrence is utilized.

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New Advances in Next-Generation Imaging: PyL PSMA PET/CT

Grand Rounds in Urology Editor-in-Chief E. David Crawford, MD, Professor of Urology at UC San Diego, interviews Peter R. Carroll, MD, MPH, Professor of Urology and Prostate Cancer at UC San Francisco, about PSMA PET/CT imaging for prostate cancer, focusing particularly on a promising new PSMA agent called PyL. The only PSMA agent currently approved for use in the United States is 68Gallium, which has a very short half-life and must be manufactured on-site. In part for this reason, 68Gallium PSMA can only be used at UCSF and UCLA. Dr. Carroll explains that PyL PSMA PET behaves similarly to 68Gallium PSMA PET, with greater sensitivity and capacity to trigger a change in treatment plans than standard imaging, but that the PyL agent is more stable, which should make it an easier product to distribute. Drs. Crawford and Carroll then consider the benefits of PSMA testing in general, noting how it could soon replace technetium bone scans as well as choline and axumin PET scans. Dr. Carroll also emphasizes PSMA PET’s role in defining the oligometastatic state. They conclude by discussing PSMA PET and theranostics.

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