National Institutes of Health State-of-the-Science Conference: Role of Active Surveillance in the Management of Men With Localized Prostate Cancer

Conferences17 April 2012National Institutes of Health State-of-the-Science Conference: Role of Active Surveillance in the Management of Men With Localized Prostate CancerFREEPatricia A. Ganz, MD, John M. Barry, MD, Wylie Burke, MD, PhD, Nananda F. Col, MD, MPP, MPH, Phaedra S. Corso, PhD, MPA, Everett Dodson, M. Elizabeth Hammond, MD, Barry A. Kogan, MD, Charles F. Lynch, MD, PhD, MS, Lee Newcomer, MD, MHA, Eric J. Seifter, MD, Janet A. Tooze, PhD, MPH, Kasisomayajula Viswanath, PhD, and Hunter Wessells, MD*Patricia A. Ganz, MDFrom University of California, Los Angeles, Schools of Medicine and Public Health and Jonsson Comprehensive Cancer Center, Los Angeles, California; Oregon Health & Science University, Portland, Oregon; University of Washington and University of Washington School of Medicine, Seattle, Washington; University of New England, Biddeford, Maine; Shared Decision Making Resources, Georgetown, Maine; University of Georgia, Athens, Georgia;Lombardi Comprehensive Cancer Center and Georgetown University Hospital, Washington, DC; Intermountain Healthcare, University of Utah School of Medicine, and Amirsys, Salt Lake City, Utah; Albany Medical College and Urological Institute of Northeastern New York, Albany, New York; The University of Iowa, Iowa City, Iowa; United Healthcare, Minneapolis, Minnesota; The Johns Hopkins University School of Medicine and The Sidney Kimmel Comprehensive Cancer Center, Lutherville, Maryland;Wake Forest School of Medicine, Winston-Salem, North Carolina; and Harvard School of Public Health and Dana-Farber Cancer Institute, Boston, Massachusetts.Search for more papers by this author, John M. Barry, MDFrom University of California, Los Angeles, Schools of Medicine and Public Health and Jonsson Comprehensive Cancer Center, Los Angeles, California; Oregon Health & Science University, Portland, Oregon; University of Washington and University of Washington School of Medicine, Seattle, Washington; University of New England, Biddeford, Maine; Shared Decision Making Resources, Georgetown, Maine; University of Georgia, Athens, Georgia;Lombardi Comprehensive Cancer Center and Georgetown University Hospital, Washington, DC; Intermountain Healthcare, University of Utah School of Medicine, and Amirsys, Salt Lake City, Utah; Albany Medical College and Urological Institute of Northeastern New York, Albany, New York; The University of Iowa, Iowa City, Iowa; United Healthcare, Minneapolis, Minnesota; The Johns Hopkins University School of Medicine and The Sidney Kimmel Comprehensive Cancer Center, Lutherville, Maryland;Wake Forest School of Medicine, Winston-Salem, North Carolina; and Harvard School of Public Health and Dana-Farber Cancer Institute, Boston, Massachusetts.Search for more papers by this author, Wylie Burke, MD, PhDFrom University of California, Los Angeles, Schools of Medicine and Public Health and Jonsson Comprehensive Cancer Center, Los Angeles, California; Oregon Health & Science University, Portland, Oregon; University of Washington and University of Washington School of Medicine, Seattle, Washington; University of New England, Biddeford, Maine; Shared Decision Making Resources, Georgetown, Maine; University of Georgia, Athens, Georgia;Lombardi Comprehensive Cancer Center and Georgetown University Hospital, Washington, DC; Intermountain Healthcare, University of Utah School of Medicine, and Amirsys, Salt Lake City, Utah; Albany Medical College and Urological Institute of Northeastern New York, Albany, New York; The University of Iowa, Iowa City, Iowa; United Healthcare, Minneapolis, Minnesota; The Johns Hopkins University School of Medicine and The Sidney Kimmel Comprehensive Cancer Center, Lutherville, Maryland;Wake Forest School of Medicine, Winston-Salem, North Carolina; and Harvard School of Public Health and Dana-Farber Cancer Institute, Boston, Massachusetts.Search for more papers by this author, Nananda F. Col, MD, MPP, MPHFrom University of California, Los Angeles, Schools of Medicine and Public Health and Jonsson Comprehensive Cancer Center, Los Angeles, California; Oregon Health & Science University, Portland, Oregon; University of Washington and University of Washington School of Medicine, Seattle, Washington; University of New England, Biddeford, Maine; Shared Decision Making Resources, Georgetown, Maine; University of Georgia, Athens, Georgia;Lombardi Comprehensive Cancer Center and Georgetown University Hospital, Washington, DC; Intermountain Healthcare, University of Utah School of Medicine, and Amirsys, Salt Lake City, Utah; Albany Medical College and Urological Institute of Northeastern New York, Albany, New York; The University of Iowa, Iowa City, Iowa; United Healthcare, Minneapolis, Minnesota; The Johns Hopkins University School of Medicine and The Sidney Kimmel Comprehensive Cancer Center, Lutherville, Maryland;Wake Forest School of Medicine, Winston-Salem, North Carolina; and Harvard School of Public Health and Dana-Farber Cancer Institute, Boston, Massachusetts.Search for more papers by this author, Phaedra S. Corso, PhD, MPAFrom University of California, Los Angeles, Schools of Medicine and Public Health and Jonsson Comprehensive Cancer Center, Los Angeles, California; Oregon Health & Science University, Portland, Oregon; University of Washington and University of Washington School of Medicine, Seattle, Washington; University of New England, Biddeford, Maine; Shared Decision Making Resources, Georgetown, Maine; University of Georgia, Athens, Georgia;Lombardi Comprehensive Cancer Center and Georgetown University Hospital, Washington, DC; Intermountain Healthcare, University of Utah School of Medicine, and Amirsys, Salt Lake City, Utah; Albany Medical College and Urological Institute of Northeastern New York, Albany, New York; The University of Iowa, Iowa City, Iowa; United Healthcare, Minneapolis, Minnesota; The Johns Hopkins University School of Medicine and The Sidney Kimmel Comprehensive Cancer Center, Lutherville, Maryland;Wake Forest School of Medicine, Winston-Salem, North Carolina; and Harvard School of Public Health and Dana-Farber Cancer Institute, Boston, Massachusetts.Search for more papers by this author, Everett DodsonFrom University of California, Los Angeles, Schools of Medicine and Public Health and Jonsson Comprehensive Cancer Center, Los Angeles, California; Oregon Health & Science University, Portland, Oregon; University of Washington and University of Washington School of Medicine, Seattle, Washington; University of New England, Biddeford, Maine; Shared Decision Making Resources, Georgetown, Maine; University of Georgia, Athens, Georgia;Lombardi Comprehensive Cancer Center and Georgetown University Hospital, Washington, DC; Intermountain Healthcare, University of Utah School of Medicine, and Amirsys, Salt Lake City, Utah; Albany Medical College and Urological Institute of Northeastern New York, Albany, New York; The University of Iowa, Iowa City, Iowa; United Healthcare, Minneapolis, Minnesota; The Johns Hopkins University School of Medicine and The Sidney Kimmel Comprehensive Cancer Center, Lutherville, Maryland;Wake Forest School of Medicine, Winston-Salem, North Carolina; and Harvard School of Public Health and Dana-Farber Cancer Institute, Boston, Massachusetts.Search for more papers by this author, M. Elizabeth Hammond, MDFrom University of California, Los Angeles, Schools of Medicine and Public Health and Jonsson Comprehensive Cancer Center, Los Angeles, California; Oregon Health & Science University, Portland, Oregon; University of Washington and University of Washington School of Medicine, Seattle, Washington; University of New England, Biddeford, Maine; Shared Decision Making Resources, Georgetown, Maine; University of Georgia, Athens, Georgia;Lombardi Comprehensive Cancer Center and Georgetown University Hospital, Washington, DC; Intermountain Healthcare, University of Utah School of Medicine, and Amirsys, Salt Lake City, Utah; Albany Medical College and Urological Institute of Northeastern New York, Albany, New York; The University of Iowa, Iowa City, Iowa; United Healthcare, Minneapolis, Minnesota; The Johns Hopkins University School of Medicine and The Sidney Kimmel Comprehensive Cancer Center, Lutherville, Maryland;Wake Forest School of Medicine, Winston-Salem, North Carolina; and Harvard School of Public Health and Dana-Farber Cancer Institute, Boston, Massachusetts.Search for more papers by this author, Barry A. Kogan, MDFrom University of California, Los Angeles, Schools of Medicine and Public Health and Jonsson Comprehensive Cancer Center, Los Angeles, California; Oregon Health & Science University, Portland, Oregon; University of Washington and University of Washington School of Medicine, Seattle, Washington; University of New England, Biddeford, Maine; Shared Decision Making Resources, Georgetown, Maine; University of Georgia, Athens, Georgia;Lombardi Comprehensive Cancer Center and Georgetown University Hospital, Washington, DC; Intermountain Healthcare, University of Utah School of Medicine, and Amirsys, Salt Lake City, Utah; Albany Medical College and Urological Institute of Northeastern New York, Albany, New York; The University of Iowa, Iowa City, Iowa; United Healthcare, Minneapolis, Minnesota; The Johns Hopkins University School of Medicine and The Sidney Kimmel Comprehensive Cancer Center, Lutherville, Maryland;Wake Forest School of Medicine, Winston-Salem, North Carolina; and Harvard School of Public Health and Dana-Farber Cancer Institute, Boston, Massachusetts.Search for more papers by this author, Charles F. Lynch, MD, PhD, MSFrom University of California, Los Angeles, Schools of Medicine and Public Health and Jonsson Comprehensive Cancer Center, Los Angeles, California; Oregon Health & Science University, Portland, Oregon; University of Washington and University of Washington School of Medicine, Seattle, Washington; University of New England, Biddeford, Maine; Shared Decision Making Resources, Georgetown, Maine; University of Georgia, Athens, Georgia;Lombardi Comprehensive Cancer Center and Georgetown University Hospital, Washington, DC; Intermountain Healthcare, University of Utah School of Medicine, and Amirsys, Salt Lake City, Utah; Albany Medical College and Urological Institute of Northeastern New York, Albany, New York; The University of Iowa, Iowa City, Iowa; United Healthcare, Minneapolis, Minnesota; The Johns Hopkins University School of Medicine and The Sidney Kimmel Comprehensive Cancer Center, Lutherville, Maryland;Wake Forest School of Medicine, Winston-Salem, North Carolina; and Harvard School of Public Health and Dana-Farber Cancer Institute, Boston, Massachusetts.Search for more papers by this author, Lee Newcomer, MD, MHAFrom University of California, Los Angeles, Schools of Medicine and Public Health and Jonsson Comprehensive Cancer Center, Los Angeles, California; Oregon Health & Science University, Portland, Oregon; University of Washington and University of Washington School of Medicine, Seattle, Washington; University of New England, Biddeford, Maine; Shared Decision Making Resources, Georgetown, Maine; University of Georgia, Athens, Georgia;Lombardi Comprehensive Cancer Center and Georgetown University Hospital, Washington, DC; Intermountain Healthcare, University of Utah School of Medicine, and Amirsys, Salt Lake City, Utah; Albany Medical College and Urological Institute of Northeastern New York, Albany, New York; The University of Iowa, Iowa City, Iowa; United Healthcare, Minneapolis, Minnesota; The Johns Hopkins University School of Medicine and The Sidney Kimmel Comprehensive Cancer Center, Lutherville, Maryland;Wake Forest School of Medicine, Winston-Salem, North Carolina; and Harvard School of Public Health and Dana-Farber Cancer Institute, Boston, Massachusetts.Search for more papers by this author, Eric J. Seifter, MDFrom University of California, Los Angeles, Schools of Medicine and Public Health and Jonsson Comprehensive Cancer Center, Los Angeles, California; Oregon Health & Science University, Portland, Oregon; University of Washington and University of Washington School of Medicine, Seattle, Washington; University of New England, Biddeford, Maine; Shared Decision Making Resources, Georgetown, Maine; University of Georgia, Athens, Georgia;Lombardi Comprehensive Cancer Center and Georgetown University Hospital, Washington, DC; Intermountain Healthcare, University of Utah School of Medicine, and Amirsys, Salt Lake City, Utah; Albany Medical College and Urological Institute of Northeastern New York, Albany, New York; The University of Iowa, Iowa City, Iowa; United Healthcare, Minneapolis, Minnesota; The Johns Hopkins University School of Medicine and The Sidney Kimmel Comprehensive Cancer Center, Lutherville, Maryland;Wake Forest School of Medicine, Winston-Salem, North Carolina; and Harvard School of Public Health and Dana-Farber Cancer Institute, Boston, Massachusetts.Search for more papers by this author, Janet A. Tooze, PhD, MPHFrom University of California, Los Angeles, Schools of Medicine and Public Health and Jonsson Comprehensive Cancer Center, Los Angeles, California; Oregon Health & Science University, Portland, Oregon; University of Washington and University of Washington School of Medicine, Seattle, Washington; University of New England, Biddeford, Maine; Shared Decision Making Resources, Georgetown, Maine; University of Georgia, Athens, Georgia;Lombardi Comprehensive Cancer Center and Georgetown University Hospital, Washington, DC; Intermountain Healthcare, University of Utah School of Medicine, and Amirsys, Salt Lake City, Utah; Albany Medical College and Urological Institute of Northeastern New York, Albany, New York; The University of Iowa, Iowa City, Iowa; United Healthcare, Minneapolis, Minnesota; The Johns Hopkins University School of Medicine and The Sidney Kimmel Comprehensive Cancer Center, Lutherville, Maryland;Wake Forest School of Medicine, Winston-Salem, North Carolina; and Harvard School of Public Health and Dana-Farber Cancer Institute, Boston, Massachusetts.Search for more papers by this author, Kasisomayajula Viswanath, PhDFrom University of California, Los Angeles, Schools of Medicine and Public Health and Jonsson Comprehensive Cancer Center, Los Angeles, California; Oregon Health & Science University, Portland, Oregon; University of Washington and University of Washington School of Medicine, Seattle, Washington; University of New England, Biddeford, Maine; Shared Decision Making Resources, Georgetown, Maine; University of Georgia, Athens, Georgia;Lombardi Comprehensive Cancer Center and Georgetown University Hospital, Washington, DC; Intermountain Healthcare, University of Utah School of Medicine, and Amirsys, Salt Lake City, Utah; Albany Medical College and Urological Institute of Northeastern New York, Albany, New York; The University of Iowa, Iowa City, Iowa; United Healthcare, Minneapolis, Minnesota; The Johns Hopkins University School of Medicine and The Sidney Kimmel Comprehensive Cancer Center, Lutherville, Maryland;Wake Forest School of Medicine, Winston-Salem, North Carolina; and Harvard School of Public Health and Dana-Farber Cancer Institute, Boston, Massachusetts.Search for more papers by this author, and Hunter Wessells, MD*From University of California, Los Angeles, Schools of Medicine and Public Health and Jonsson Comprehensive Cancer Center, Los Angeles, California; Oregon Health & Science University, Portland, Oregon; University of Washington and University of Washington School of Medicine, Seattle, Washington; University of New England, Biddeford, Maine; Shared Decision Making Resources, Georgetown, Maine; University of Georgia, Athens, Georgia;Lombardi Comprehensive Cancer Center and Georgetown University Hospital, Washington, DC; Intermountain Healthcare, University of Utah School of Medicine, and Amirsys, Salt Lake City, Utah; Albany Medical College and Urological Institute of Northeastern New York, Albany, New York; The University of Iowa, Iowa City, Iowa; United Healthcare, Minneapolis, Minnesota; The Johns Hopkins University School of Medicine and The Sidney Kimmel Comprehensive Cancer Center, Lutherville, Maryland;Wake Forest School of Medicine, Winston-Salem, North Carolina; and Harvard School of Public Health and Dana-Farber Cancer Institute, Boston, Massachusetts.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-156-8-201204170-00010 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail National Institutes of Health (NIH) Consensus and State-of-the-Science Statements are prepared by independent panels of health professionals and public representatives on the basis of 1) the results of a systematic literature review prepared under contract with the Agency for Healthcare Research and Quality, 2) presentations by investigators working in areas relevant to the conference questions during a 2-day public session, 3) questions and statements from conference attendees during open discussion periods that are part of the public session, and 4) closed deliberations by the panel during the remainder of the second day and morning of the third. This statement is an independent report of the panel and is not a policy statement of NIH or the U.S. government.The statement reflects the panel's assessment of medical knowledge available at the time the statement was written. Thus, it provides a “snapshot in time” of the state of knowledge on the conference topic. When reading the statement, keep in mind that new knowledge is inevitably accumulating through medical research. The following statement is an abridged version of the panel's report, which is available in full at consensus.nih.gov/2011/prostatefinalstatement.htmIn 2011, more than 240 000 men are projected to receive a diagnosis of prostate cancer and 33 000 are projected to die of this condition. More than 2.5 million men in the United States are long-term survivors of prostate cancer. Men with a strong family history of prostate cancer and African American men are at increased risk for prostate cancer. Most cases of prostate cancer are localized at diagnosis and detected as a result of screening with prostate-specific antigen (PSA) testing. Most of these screen-detected cases of cancer are low risk and are unlikely to cause death. The natural history of prostate cancer has changed dramatically in the past 3 decades because of PSA screening.Although most cases of prostate cancer are slow-growing and unlikely to spread, most men receive immediate treatment with surgery or radiation. These therapeutic strategies are associated with short- and long-term complications, including impotence and urinary incontinence. Only a few men choose observational strategies, thereby delaying the initiation of curative therapy or avoiding it completely. Given the high prevalence of low-risk prostate cancer, the roles of active surveillance and other observational strategies as alternatives to immediate treatment need to be clarified.The National Cancer Institute, the Centers for Disease Control and Prevention, and the NIH Office of Medical Applications of Research convened a State-of-the-Science Conference on 5 to 7 December 2011 to assess the available scientific evidence about active surveillance for men with localized prostate cancer. The conference, which addressed 5 key questions, was informed by a formal evidence report commissioned through the Agency for Healthcare Research and Quality, data presented by speakers, and input from attendees.Question 1How have the patient population and the natural history of prostate cancer diagnosed in the United States changed in the past 30 years?Before the adoption of PSA screening, most cases of prostate cancer were detected because of symptoms of advanced cancer or a nodule found on digital rectal examination. These symptomatic tumors were usually high-grade and advanced and were often fatal. Other tumors were found incidentally at the time of surgery for benign enlargement of the prostate. These were often low-grade and localized.After the introduction of PSA screening in 1987, there was a spike in the rate of prostate cancer cases detected, followed by a persistent elevation over the pre–PSA testing era but no increase in prostate cancer deaths. Other 20-year follow-up studies indicate that only 5% of these men die of prostate cancer.All of these trends led to the need to modify the approach to diagnosis and treatment of prostate cancer. Today, most cases of prostate cancer are diagnosed by examining multiple core-needle biopsy specimens, which are graded by using a prognostic system called Gleason scoring. In this system, the arrangement of tumor cells is given a pattern designation ranging from 1 (lowest) to 5 (highest) on the basis of their relationship to normal prostate gland cells. Each tumor is assigned 2 pattern grades: the most frequently seen grade and the highest grade in the nondominant area. The pattern numbers are then added to provide a pathologic diagnosis called the Gleason score. For example, if the most common tumor pattern was grade 3 and the next most common was grade 4, the Gleason score would be 3 + 4 = 7. Gleason scores are considered the most powerful indication of the patient's expected outcome and are commonly used to define treatment strategies. A Gleason score of 3 + 3 = 6 is the lowest score usually given in core-needle biopsy specimens. Although Gleason scoring is the most important diagnostic tool, the method is subject to interobserver variation and difficulties with sampling because biopsy samples constitute less than 0.5% of prostate tissue even when multiple cores are obtained.Since the initiation of PSA screening, more cases of low-risk prostate cancer have been detected, and by 2002, more than 63% of all cases of prostate cancer detected in 1 large series were Gleason 3 + 3 = 6. The percentage of cases labeled as having a Gleason score of 6 has probably increased since that time. Gleason score changes parallel the increased number of patients with prostate cancer who have PSA values less than 10 µg/L.Decisions about prostate cancer treatment depend on accurate pathologic diagnosis. We need to ensure the level of agreement of Gleason scoring among physicians who examine prostate tissue so that scoring results are consistent. Additional research is needed to evaluate prostate cancer biomarkers that are different from PSA and are predictive of cancer behavior.Question 2How are active surveillance and other observational strategies defined?Two observational strategies exist: active surveillance and watchful waiting. These terms have evolved over time and have not been consistently applied. Active surveillance is a disease-management strategy that delays curative treatment until it is warranted on the basis of defined indicators of disease progression. In contrast, watchful waiting is a strategy that forgoes curative treatment and initiates intervention only when symptoms occur.The 3 components of a given observational management strategy are eligibility criteria, follow-up protocols to monitor disease progression, and indicators for treatment. The evidence report identified 16 studies that meet the definition of active surveillance and another 13 that followed patients who did not receive treatment and were followed for symptom progression (watchful waiting).The most widely accepted criterion for active surveillance eligibility is the presence of low-risk, clinically localized prostate cancer. Characteristics commonly used to identify such low-risk tumors include tumor stage (T1c, PSA detected; T2a, small palpable nodule), PSA value (<10 µg/L), Gleason score (≤6), and extent of disease on biopsy. Patient characteristics have been used inconsistently to determine eligibility and include age and overall health status, which reflect life expectancy.Watchful waiting, which predated active surveillance as an observational strategy, was based on the recognition that death from other causes exceeded death from prostate cancer in men with shorter life expectancies. Thus, watchful waiting studies used less-rigid eligibility criteria, accommodating men who were older, had more chronic illnesses, or preferred less invasive treatment. These criteria, although similar to those used in active surveillance, allow for inclusion of men with higher PSA values and higher clinical stage tumors in the absence of metastatic disease.The purpose of the active surveillance follow-up protocol is to detect disease progression. In previous studies, follow-up assessments included PSA level, digital rectal examination, and repeated biopsy. Measurement of PSA level and digital rectal examination were performed every 3 to every 12 months, but no consensus exists as to the optimal schedule. Repeated biopsy is included in all U.S. studies of active surveillance to detect disease progression and misclassification of the original biopsy specimen. The frequency varies from 1 to 4 biopsy procedures during the initial 4-year period, with surveillance continuing indefinitely.The intention of follow-up strategies differs between active surveillance and watchful waiting. In watchful waiting, intervention is reserved for relief of symptomatic disease progression. Therefore, follow-up of prostate cancer in patients managed with watchful waiting is minimal.Indicators of disease progression that may lead to the recommendation for curative treatment under active surveillance include increased Gleason score on repeated biopsy (for example, a Gleason score ≥7), shorter time for doubling of PSA level (for example, a doubling time <3 years may indicate the need for repeated biopsy), or increased extent of disease (more of the biopsied tissues involved with cancer) on biopsy. Men receiving active surveillance may opt to undergo curative treatment at any time; no studies formally define or measure patient factors or preferences leading to abandoning active surveillance for curative treatment.In contrast, the development of symptoms (such as urinary obstruction, pain, or bony fractures) is the primary indication for treatment under watchful waiting. Some patients do opt for treatment on the basis of individual preferences; however, these choices are not well-studied.More research is needed about the 2 broad categories of observational follow-up, active surveillance and watchful waiting, particularly because each has variable protocols. As the methods are further developed and refined, new terminology may be needed to distinguish consensus-based methods from historical practices and to offer patients the appropriate strategy for their prostate cancer.Tumor characteristics derived from the prostate biopsy have been the mainstay to determine eligibility for active surveillance of men with tumors at low and very low risk. The minimum number of biopsy cores required for representative sampling of the prostate and the value of normalizing PSA values to prostate volume need clarification. Alternatives to Gleason scoring are needed to best identify candidates for active surveillance, to avoid sampling error, and to reduce misclassification of tumors.Patient characteristics should be measured with standardized self-reporting instruments and be integrated into decisions about eligibility. Such characteristics include attitudes and preferences with regard to general and disease-specific quality of life, life expectancy, and anxiety about cancer diagnosis.Follow-up under active surveillance varies and is not currently evidence-based. The types of monitoring and their optimal frequency need to be defined. It is important to consider whether follow-up should vary on the basis of tumor and patient characteristics. Alternatives to repeated biopsy should be investigated to reduce morbidity and encourage adherence to active surveillance. However, such new technologies must balance cost and burden to the patient. Follow-up also should monitor ongoing patient concerns with risk for complications, anxiety, and worry about progression.Predicting whether a particular person's cancer will progress is difficult. The only clear current indicator of disease progression is an increase in Gleason score. The value of PSA level doubling time is uncertain. New indicators of disease progression are needed, such as imaging techniques to identify clinically important tumors, molecular classification of types of cancer, and genetic classification of a patient's risk for progression.Question 3What factors affect the offer of, acceptance of, and adherence to active surveillance?Active surveillance is underused as a treatment strategy in men with low-risk prostate cancer, for reasons that are not fully understood. Studies addressing the offer of, acceptance of, and adherence to active surveillance have important limitations. Many studies are small, are unlikely to be representative, and evaluate a limited number of societal and individual factors. These limitations make it difficult to draw clear inferences, but the available data suggest the following.Offer of Active SurveillanceObservational strategies are not consistently discussed as a treatment option for localized prostate cancer. When active surveillance is included as a treatment option, it may be presented in a negative way (for example, by characterizing an observational approach as “doing nothing”). Unfavorable presentations of active surveillance may reflect physician opinion but also may be an unintended consequence of a specialist's perspective and training. Clinical factors also influence the offer of observational treatment. Physicians are more likely to recommend an observational strategy for men with low-risk di