Nomenclature Matters: What Should the Future Be for Gleason Grade Group 1?

Matt Cooperberg | November 30, 2022

The term “cancer” dates to the time of Hippocrates, when the crab (karkinos)-like cutaneous manifestations of advanced tumors heralded incurable disease, pain, decline, and death. Today the term denotes an incredibly diverse spectrum of conditions, all characterized by abnormal cell division and growth—and nearly all by the capacity for metastasis—but varying very widely in aggressiveness and kinetics of progression. In the era of microscopy and histopathology, each cancer now has its formal criteria for diagnosis, and clinicians recognize the variable meaning of each. To the public, however, the connotation of the diagnosis “You have cancer” has changed only to an extent in the modern age.

In the case of prostate cancer, prostate specific antigen (PSA)-based early detection and the years-to-decades lead time associated with screening has radically changed the clinical meaning of the diagnosis. Countless research articles and reviews on prostate cancer begin by citing the fact that it is the most common non-cutaneous cancer diagnosed among men in the US and in many other countries.

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Matthew R. Cooperberg, MD, MPH

Matthew R. Cooperberg, MD, MPH graduated from Dartmouth College, where he finished summa cum laude with a major in English. He earned his MD and MPH degrees at Yale University and completed residency in Urology and fellowship in Urologic Oncology at UCSF. At the end of his training, Dr. Cooperberg joined the faculty at UCSF, where he maintains busy clinical practices at the UCSF Helen Diller Family Comprehensive Cancer Center and the San Francisco VA Medical Center. He also holds a secondary appointment in the Department of Epidemiology & Biostatistics. He is actively engaged in research approaching the challenges of prostate cancer from many interrelated angles, from molecular analyses to health system-wide research. He has written or contributed to over 350 research articles. Early in 2013 Dr. Cooperberg co-authored a proposal for a national urology registry which served as the basis for the AUA Quality (AQUA) Registry, a project for which he now serves as Senior Physician Advisor. In 2015 he won the AUA Gold Cystoscope Award, and in 2016 was awarded his first R01 grant as Principal Investigator from the National Cancer Institute, to develop and validate novel miRNA-based biomarker signatures for refined prostate cancer prognosis. He lives in San Francisco with his wife, Jacqueline Dolev (a derm-atologist and fellow Yale Medical School alum), where they work primarily to keep up with their children, Jake and Sarah.

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Written by Christopher J.D. Wallis, MD PhD, Rashid Sayyid, MD MSc, & Zachary Klaassen, MD MSc
January 6, 2023

External beam radiotherapy, along with radical prostatectomy, has been a mainstay treatment option for prostate cancer for decades and is currently recommended by numerous guidelines for the treatment of intermediate- and high-risk disease.1-3 Unlike surgery which is often, at least initially, planned as a monotherapy, many patients who opt for external beam radiotherapy will receive concurrent therapy. This center of excellence article will review the evidence for concurrent systemic therapy with radiotherapy in men with localized and locally advanced disease.

Written by Christopher J.D. Wallis, MD PhD, Rashid Sayyid, MD MSc, & Zachary Klaassen, MD MSc
December 13, 2022

External beam radiotherapy, along with radical prostatectomy, has been a mainstay treatment option for prostate cancer and is currently recommended by numerous guidelines for the treatment of intermediate- and high-risk disease.1-3 While external beam radiotherapy has been foundational in prostate cancer treatment for decades, there have been significant changes in the delivery of radiotherapy, corresponding to technical advances.

Written by Christopher J.D. Wallis, MD, PhD & Zachary Klaassen, MD, MSc
December 8, 2021

Active Surveillance Background


Prostate cancer represents a public health dilemma: while prostate cancer is the second leading cause of death among men in the US1 and third in Canada,2 it is widely over-diagnosed and over-treated, leading to significant patient anxiety and morbidity.3 Much of the over-diagnosis of prostate cancer relates to the use of serum prostate-specific antigen (PSA) testing for prostate cancer screening, beginning in 1987.4
Written by David Crawford, MD
December 8, 2021

Over the nearly two years of navigating the COVID pandemic, urology practices were forced to increase their efficiency by focusing on streamlining patient visits without sacrificing care quality. However, postponed checkups were unavoidable as the public was encouraged to stay home. According to the Centers for Disease Control and Prevention (CDC), 40% of Americans in 2020 delayed or avoided medical care due to pandemic-related concerns. Although necessary, we are now facing the severe consequences of delayed diagnosis and prostate cancer seems to be leading the way.

November 8, 2021
In prostate pre- and post-biopsy decision making, more precision is urgently needed. Whereas expert imaging and biomarker-based risk scores already enable the clinician in this respect, the dilemma remains for those patients that are diagnosed with apparent indolent cancer. Additional diagnostic tools that (de)select patients for active surveillance (AS) would provide a great benefit for the patient.
Written by Neal D. Shore, MD, FACS, and Michael S. Cookson, MD, MMHC
October 12, 2020
The COVID-19 pandemic has resulted in numerous physical and psychological adjustments for clinicians, patients, and their families—wearing personal protective equipment, adopting telemedicine, adjusting clinic workflow, etc. The ensuing uncertainty and attendant anxiety from the fluidity of information and healthcare policy debate has augmented the need for enhanced communication
Written by Neal D. Shore, MD, FACS, and Michael S. Cookson, MD, MMHC
June 24, 2020
Despite the recent disruptions in health care delivery due to the COVID-19 pandemic, patients at risk for developing prostate cancer as well as those diagnosed with prostate cancer still deserve timely and optimal decision making.
Written by Zachary Klaassen, MD, MSc and Christopher J.D. Wallis, MD, PhD
April 20, 2020
Currently, there is a global pandemic surrounding the spread of betacoronavirus SARS-CoV-2 leading to Coronavirus Disease 2019 (COVID-19). The rapid spread to all corners of the globe has had tremendous health and economic implications, including the appropriate allocation of healthcare resources.
Written by Christopher J.D. Wallis, MD, PhD and Zachary Klaassen, MD, MSc
April 17, 2020
The rapid spread of Coronavirus Disease 2019 (COVID-19) throughout the world, caused by the betacoronavirus SARS-CoV-2, has had dramatic effects on health care systems with impacts far beyond the patients actually infected with COVID-19. Patients who manifest severe forms of COVID-19 requiring respiratory support typically require this for prolonged durations, with a mean of 13 days of respiratory support reported by the China Medical Treatment Expert Group for Covid-19.1
Written by Zachary Klaassen, MD, MSc and Christopher J.D. Wallis, MD, PhD
March 19, 2020
Radiographic imaging has played a key role in the diagnosis and staging of patients with prostate cancer for decades. Today, transrectal ultrasound and multiparametric magnetic resonance imaging are important in diagnosis and local staging of the primary tumor while axial imaging and molecularly targeted positron emission tomography
Written by Zachary Klaassen, MD, MSc
April 16, 2019
Secondary to the introduction of prostate specific antigen (PSA) screening in the 1980’s/1990’s, symptomatic presentation of prostate cancer has become less frequent. Symptoms of locally advanced prostate cancer may include obstructive urinary symptoms, gross hematuria, and/or upper tract urinary obstruction leading to renal failure.
Written by Zachary Klaassen, MD, MSc
April 16, 2019
Over the last decade, imaging for prostate cancer has improved immensely. Specifically, prostate multiparametric MRI (mpMRI) has improved primarily as a result of an increase in magnet strength from 1 to 3-tesla. mpMRI consists of anatomic and functional imaging techniques:
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Written by Leonardo K. Bittencourt, Anwar R. Padhani, Clare M. Tempany, & Ivo G. Schoots
The wide adoption of MRI and MRI-directed biopsies in the diagnostic workup of suspected prostate cancer (PCa) has ignited discussions about the appropriate balance between the benefits and harms of the biopsy decisions.
Written by Udit Singhal, MD, and Randy A. Vince Jr., MD, MS
Genomic classifiers are used for prognostication and risk stratification in prostate cancer. Despite the emerging data, a commonly cited limitation is the retrospective datasets used for analysis. While there has been a litany of data using retrospective datasets to extrapolate the value of commercially available platforms in the pretreatment setting, the evaluation of these assays using prospectively collected data is still needed.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Germline DNA damage repair (gDDR) alterations are common in men with prostate cancer (PCa). Men with PCa and gDDR alterations showed poor clinical outcomes. It is unclear if men with high-risk PCa and gDDR alterations would respond differently to neoadjuvant androgen
Conference Coverage
Conference Highlights Written by Physician-Scientist
Presented by Ashley E. Ross, MD, PhD
The 23rd Annual Meeting of the SUO was host to a prostate cancer session. Dr. Ashley Ross, MD, PhD presented the results of an external validation of a digital pathology-based artificial intelligence (AI) model predicting metastasis and death in high and very high risk men from the NRG/RTOG 9902 phase III trial.
Presented by Alan Dal Pra, MD
The 2022 ASTRO Annual Meeting was host to a session evaluating new insights into post-prostatectomy radiotherapy. Dr. Dal Pra presented his group’s work evaluating the prognostic and predictive performance of a 24-gene post-operative radiation therapy outcomes score (PORTOS) in a phase III randomized trial of dose-intensified salvage radiotherapy after radical prostatectomy (SAKK 09/10).
Presented by Zaeem Lone, MD
The 2022 ASTRO annual meeting featured an improving prostate cancer survival session, including a presentation by Zaeem Lone discussing transcriptomic features of cribriform and intraductal carcinoma of the prostate. Prostate cancer risk stratification has largely relied upon Gleason grade and PSA level. However, recent recommendations from the International Society of Urologic Pathologists has suggested modifying the Gleason grade system to include reporting of cribriform and intraductal carcinoma.  The objective of this study presented at ASTRO 2022 was to identify any correlations between Decipher genomic risk score and cribriform and intraductal carcinoma status while also assessing prostate cancer transcriptomic features of these pathologic features.
Presented by Skyler B. Johnson, MD
The 2022 ASTRO annual meeting featured an improving prostate cancer survival session, including a presentation by Dr. Skyler Johnson discussing the impact of tertiary Gleason pattern 5 and high Genomic Classifier Score on predicting lymph node invasion at the time of radical prostatectomy in patients with intermediate-risk disease.  Dr. Johnson and colleagues hypothesized that tertiary Gleason pattern 5, and a Genomic classifier, could improve prognostication of lymph node invasion after radical prostatectomy over traditional clinicopathologic risk factors alone.
Presented by Alicia K. Morgans, MD, MPH
The 2022 ASCO annual meeting featured a session on prostate cancer, including a trial in progress presentation by Dr. Alicia Morgans discussing ERADICATE, a phase III double blinded study of early intervention after radical prostatectomy with ADT with darolutamide versus placebo in men at highest risk of prostate cancer metastasis by genomic stratification.
Presented by James Eastham, MD
The 2022 Annual Meeting of the American Urological Association was host to an AUA Guidelines sessions focused on localized prostate cancer, presented by Dr. James Eastham. The guidelines were divided into multiple sections:
In this plenary session, Dr. Jeffrey Cadeddu, Dr. Jihad Kaouk, and Dr. Li-Ming Su elaborated on the specific advantages and disadvantages of the multiport (MP) and single port (SP) robotic platforms in performing prostatectomies in hopes of delineating one’s superiority over the other. Of note, Dr. Cadeddu and Dr. Kaouk, who were both arguing counterpoints, have experience with both robotic platforms.
Presented by Kostantinos Morris, Judd Moul, MD, Srinath Kotamarti, MD,
The 2022 American Urological Association (AUA) Annual Meeting featured work from Mr. Kostantinos Morris and colleagues from Duke University School of Medicine (Durham, North Carolina) assessing the usage of prostate health index (PHI) in pre-biopsy work-up of African-American men.
Presented by Brandon Mahal, MD
The 2022 Advanced Prostate Cancer Consensus Conference (APCCC) Hybrid Meeting included a session on biochemical recurrence and a presentation by Dr. Brandon Mahal discussing who needs systemic treatment with salvage radiotherapy. Dr. Mahal started his presentation by highlighting the RTOG 9601 trial,1 
Presented by Felix Feng, MD

(UroToday.com) The 2022 Advanced Prostate Cancer Consensus Conference (APCCC) Hybrid Meeting included a session on biochemical recurrence, and a presentation by Dr. Felix Feng discussing how treatment can be individualized by using genomic classifiers. Dr. Feng started by highlighting that genomic biomarkers are included in certain treatment 

Presented by Christopher Koller, MD
The 2022 Southeastern Section of the AUA’s annual meeting included a prostate cancer session and Dr. Christopher Koller discussing a prospective observational prostate cancer study assessing the potential for upgrading on active surveillance among African American men.
Presented by Christopher Koller, MD
The 2022 Southeastern Section of the AUA’s annual meeting included a prostate cancer session and Dr. Christopher Koller discussing the impact of COVID-19 on adhering patients to an active surveillance protocol for prostate cancer.
Presented by J Kellogg Parsons, MD, MHS,
Dr. Parsons presented a poster describing the results of the IPASS study examining the role of PROSTVAC immunotherapy in patients eligible for active surveillance. A significant proportion of men who begin active surveillance will have disease progression.
Presented by Daniel Spratt, MD
Dr. Dan Spratt presented a poster outlining validation of the Decipher biopsy genomic classifier in intermediate-risk prostate cancer. The 22-gene Decipher genomic classifier (GC) is a prognostic biomarker that has been validated in phase III trials in high-risk localized, 
Presented by Alan Dal Pra, MD

The 2021 ASTRO Meeting included a session on biomarkers and salvage radiotherapy and discussion by Dr. Alan Dal Pra regarding the performance of a genomic classifier within a phase 3 randomized trial of dose escalated salvage radiotherapy after radical prostatectomy.

Presented by Paul Nguyen, MD

The 2021 ASTRO Meeting included a session on biomarkers and salvage radiotherapy and discussion by Dr. Paul Nguyen regarding the validation of a 22-gene genomic classifier in the NRG Oncology/RTOG 9202, 9413, and 9902 phase III randomized trials.

Presented by Brian Baumann, MD

The 2021 ASTRO Meeting’s included a session on biomarkers and salvage radiotherapy and a discussant presentation of five presentations in this session by Dr. Brian Baumann. With regards to organizing these five presentations into clinical context, Dr. Baumann highlighted the SAKK 09/10 trial, a phase I trial of neoadjuvant stereotactic body radiotherapy, biomarker studies

Presented by Chris H. Bangma, MD, PhD
In this presentation, Dr. Chris Bagma, Professor of Urology at Erasmus MC, focused on anxiety and quality-of-life for men on active surveillance for prostate cancer. First, he started by reviewing active surveillance. Active surveillance (AS) is a treatment option for low-risk prostate cancer per the EAU and AUA guidelines. 
Presented by David Monty Berman, MD
In plenary abstract presentation at the 2021 ASCO GU, Dr. Berman and colleagues present their work which sought to create objective molecular biomarkers that would be resistant to sampling error and should be useful when applied to biopsy tissue, on the basis of radical prostatectomy grade.
In a plenary abstract presentation in the Poster Highlights Session: Prostate Cancer - Localized Disease session at the 2021 ASCO GU meeting, Dr. Fairmichael and colleagues presented results of the Stereotactic Prostate Radiotherapy (SPORT) trial, examining the feasibility of performing a randomized trial of SABR ± PNI.
Presented by Jim Hu, MD, MPH
In the session on prostate cancer, Jim Hu, MD, MPH, discussed the Study of Prostate Ablation Related Energy Devices (SPARED) Collaboration.
Presented by Ivo Schoots, MD, PhD
San Francisco, CA  (UroToday.com)  Dr. Ivo Schoots from the Netherlands discussed the optimal use of multiparametric MRI in the management of localized prostate cancer.
Presented by Laurence H. Klotz, MD, FRCSC
Washington, DC (UroToday.com) The recipient of this year’s Huggins Medal is Dr. Laurence Klotz from the University of Toronto and Sunnybrook Medical Centre. Dr. Klotz has 470
Presented by Matthew R Cooperberg, MD, MPH, FACS
Washington, DC (UroToday.com) In the first prostate cancer session at the 2019 Society for Urologic Oncology meeting in Washington, DC, Dr. Matthew Cooperberg highlighted the similarities
Presented by Ganesh S. Palpattu, MD, FACS
Athens, Greece (Urotoday.com) In today’s medical environment of the growing number of patients, increasing complexity of patient problems, an ever-growing body of literature
Presented by Derya Tilki, MD
Athens, Greece (Urotoday.com) In this talk, Dr. Tilki reviewed several prognostic biomarkers in the setting of localized prostate cancer management. 
Presented by Andre Abreu, MD
Athens, Greece (UroToday.com) Cryoablation involves freezing of the targeted prostate tissue in two cycles, reaching minus 40 degrees Celsius, with the following histological changes:
Presented by Professor Christopher Parker
Barcelona, Spain (UroToday.com) Men who undergo surgery as definitive therapy for their localized prostate cancer generally only receive subsequent radiation therapy
Presented by Claire Vale, PhD
Barcelona, Spain (UroToday.com) There are three randomized trials, RADICALS,1 GETUG-AFU 17 and RAVES; recently presented at ASTRO 2019, that have compared adjuvant radiotherapy with a policy of salvage radiotherapy
Presented by Zachary Kornberg, Staff Research Associate
Chicago, IL (UroToday.com) Dr. Kornberg presented his talk on- A 17-gene Genomic Prostate Score as a Predictor of Adverse Pathology for Men on Active Surveillance. The Oncotype DX® Genomic Prostate Score (GPS) test is an RNA expression assay that can be performed on needle-core biopsies from men with prostate cancer (PCa).
Presented by Zachary Klaassen, MD, MSc
Barcelona, Spain (UroToday.com) At the Active Surveillance vs Focal Therapy in Prostate Cancer session at EAU 2019, Dr. Francesco Giganti and colleagues from the United Kingdom presented results of their use of the PRECISE recommendations and outcome of men on active surveillance for prostate cancer. 
Presented by Roderick van den Bergh, MD
Barcelona, Spain (UroToday.com) Dr. van den Bergh presented on the current and future role of active surveillance in prostate cancer. Approximately 350 studies on active surveillance have been published per year in the last 5 years. This therapeutic strategy has been incorporated into all major urological guidelines
Presented by Guan Hee Tan, Clinical Fellow
Barcelona, Spain (UroToday.com) Active Surveillance (AS) for prostate cancer (PCa) is the standard of care of men with low-risk PCa. However, approximately 30-40% of men on AS will eventually progress to treatment – either due to choice or due to progression. Progression can either be due to grade or volume progression
Presented by Monique J. Roobol, PhD., MSc
Prague, Czech Republic (UroToday.com) As part of the ESOU 2019 prostate cancer session there was a discussion regarding the appropriate treatment of Gleason 3+4 disease. Dr. Monique Roobol discussed the possible utilization of active surveillance for these patients.
Presented by Nicolas Mottet, MD, Ph.D
Prague, Czech Republic (UroToday.com) It is good news for both patients and physicians that there has been wider adoption of appropriate utilization of active surveillance (AS) among patients with prostate cancer. Dr. Nicolas Mottet presented risk stratification for active surveillance.
Presented by Laurence Klotz, MD, FRCSC
Toronto, Ontario (UroToday.com) Dr. Laurence Klotz presented on the current status of active surveillance for prostate cancer. Through the years there has been greater recognition of the overtreatment problem of prostate cancer patients, and the concept of active surveillance has been more accepted.
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