Guideline for the Management of Clinically Localized Prostate Cancer: 2007 Update (2007)

You have accessJournal of UrologyAdult urology1 Jun 2007Guideline for the Management of Clinically Localized Prostate Cancer: 2007 Updateis accompanied byQuantifying the Impact of Prostate Volumes, Number of Biopsy Cores and 5α-Reductase Inhibitor Therapy on the Probability of Prostate Cancer Detection Using Mathematical Modeling Ian Thompson, James Brantley Thrasher, Gunnar Aus, Arthur L. Burnett, Edith D. Canby-Hagino, Michael S. Cookson, Anthony V. D’Amico, Roger R. Dmochowski, David T. Eton, Jeffrey D. Forman, S. Larry Goldenberg, Javier Hernandez, Celestia S. Higano, Stephen R. Kraus, Judd W. Moul, Catherine M. Tangen, and Prostate Cancer Clinical Guideline Update Panel Ian ThompsonIan Thompson Financial interest and/or other relationship with Mission Pharmacal, AstraZeneca and National Institutes of Health. More articles by this author , James Brantley ThrasherJames Brantley Thrasher Financial interest and/or other relationship with Medidiom and Abbott. More articles by this author , Gunnar AusGunnar Aus Financial interest and/or other relationship with Bok Medical. More articles by this author , Arthur L. BurnettArthur L. Burnett Financial interest and/or other relationship with Pfizer, Lilly ICOS and Guilford/MOI Pharma. More articles by this author , Edith D. Canby-HaginoEdith D. Canby-Hagino More articles by this author , Michael S. CooksonMichael S. Cookson Financial interest and/or other relationship with Sanofi-Aventis, GlaxoSmithKline, Envisioneering Medical Technologies, Aeterna Zentaris Solvay, Photocure, National Institutes of Health and GTX. More articles by this author , Anthony V. D’AmicoAnthony V. D’Amico More articles by this author , Roger R. DmochowskiRoger R. Dmochowski Financial interest and/or other relationship with Indevus, Watson Pharmaceuticals and Bard. More articles by this author , David T. EtonDavid T. Eton More articles by this author , Jeffrey D. FormanJeffrey D. Forman More articles by this author , S. Larry GoldenbergS. Larry Goldenberg More articles by this author , Javier HernandezJavier Hernandez More articles by this author , Celestia S. HiganoCelestia S. Higano More articles by this author , Stephen R. KrausStephen R. Kraus Financial interest and/or other relationship with National Institute for Diabetes and Digestive and Kidney Diseases, Pfizer, Atellas, Novartis and Ortho McNeil. More articles by this author , Judd W. MoulJudd W. Moul Financial interest and/or other relationship with AstraZeneca, Pfizer, Sanofi-Aventis and GlaxoSmithKline. More articles by this author , Catherine M. TangenCatherine M. Tangen More articles by this author , and Prostate Cancer Clinical Guideline Update Panel More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2007.03.003AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail Introduction In December 1995, the AUA published the Report on the Management of Clinically Localized Prostate Cancer.1 The document was the culmination of six years of work by 17 clinicians and scientists and required the evaluation of 12,501 scientific publications with the detailed extraction of information from 165 papers that met the rigorous criteria of the panel of experts (Appendix 1 on-line). The Panel noted that a lack of evidence precluded specific recommendations for optimal treatment of an individual patient, which patients should be offered all treatment options, and that patient preferences should guide decision making. Since 1995, approximately 2,600,000 men2 in the United States have been diagnosed with prostate cancer, and nearly 375,000 men3,4 have lost their lives to this disease. In addition, the National Cancer Institute4 has spent $2.1 billion on prostate cancer research and as of November 2005, approximately 28,111 scientific papers concerning prostate cancer have been published in peer-reviewed medical journals (OVID Search, December 31, 1995 to October 23, 2005; key word: prostatic neoplasms). At the same time, mortality rates from prostate cancer have been declining: 34,475 men died in 1995 compared with an estimated 30,350 in 2005.4 Several pivotal RCTs related to prostate cancer treatment have been completed, including a chemoprevention study,5 along with studies demonstrating prolongation of life in men with hormone-refractory metastatic disease6,7 and improved outcomes in men with nonmetastatic disease.8–35 With the use of new and combined treatments, the frequency and variety of complications have differed from those previously reported. Advances have been made in prostate cancer imaging, biopsy methodology, in understanding causative factors and disease, in treatment-related QOL and in predicting the behavior of individual tumors using risk strata. Despite these advances, no consensus has emerged regarding the optimal treatment for the most common patient with prostate cancer: the man with clinically localized stage T1 to T2 disease with no regional lymph node or distant metastasis (T1 to T2N0-NxM0). Of the 234,460 men in the United States diagnosed with prostate cancer annually, 91% have localized disease.36 For these men and their families, the bewildering array of information from scientific and lay sources offers no clear-cut recommendations. Understanding this challenge for patients with newly diagnosed localized prostate cancer and the explosion in research and publications, the AUA re-impaneled the Prostate Cancer Clinical Guideline Panel (Appendix 2 on-line) for the purpose of reexamining and updating its analysis of treatment options. We herein report the results of a 5½-year effort to update the 1995 Guideline. The online version of this Guideline, which can be accessed at http://www.auanet.org/guidelines/, contains appendixes that include additional documents used in the conduct of the analysis and the graphics detailing the Panel’s findings. Context A contemporary man with localized prostate cancer is substantially different from the man with prostate cancer of 20 years ago. With the advent of PSA screening beginning in the late 1980s and the dramatic increase in public awareness of the disease, the average new prostate cancer patient has generally undergone multiple prior PSA tests and may even have experienced one or more prior negative prostate biopsies. When the cancer is detected, it is in a substantially earlier stage, often nonpalpable clinical stage T1c with, perhaps, one to several positive biopsy cores. The typical patient usually is very familiar with his PSA history and has a history of multiple visits to either his primary care provider or urologist. The most common patient will likely have Gleason score 6 or 7 disease, reflecting the most common current grading category and the fact that contemporary uropathologists assign this score more often than in the past when this group of tumors was frequently diagnosed one or two scores lower.37 The average patient of today also will more commonly have serum PSA levels in the 4 to 10 ng/mL range, and often in the 2.5 to 4.0 ng/mL range. In many cases, the patient’s PSA history will include sufficient data to allow a prediagnosis PSA velocity or doubling time to be calculated. Generally, the treating physicians will personalize the patient’s risk based on serum PSA level, highest/worst Gleason score, clinical stage, and burden of disease (either number or percent of biopsy cores with cancer). Following diagnosis, today’s patient will oftentimes be better informed and consequently request a second opinion by other physicians including other urologists or such specialists as radiation and medical oncologists. Many centers offer multidisciplinary clinics where the patient can consult with urologists, and with radiation and medical oncologists at one location. After considering the options and gathering several opinions, a patient and his family will choose among active surveillance, interstitial prostate brachytherapy, EBRT, and RP with treatment generally commencing two to three months after diagnosis. Aside from this complex decision, where the evidence basis for action has been suboptimal, patients now also are faced with subtle but important technical decisions such as choosing the type of surgery (eg open vs laparoscopic/robotic prostatectomy), the type of radiotherapy (eg conformal vs intensity modulated), the type of brachytherapy isotope, or whether a combination (eg brachytherapy and EBRT) of therapies should be used. Minimal data currently are available for the following interventions: high-intensity focused ultrasound, cryotherapy, high-dose rate interstitial prostate brachytherapy, and primary hormonal therapy. Conclusions regarding outcomes of these treatments cannot be made. It is in this very changed environment that we present the 2007 AUA Prostate Cancer Clinical Guideline Panel report. Definitions and Terminology The reader desiring a greater degree of information regarding the terminology used herein is directed to Appendix 3 on-line, which provides a glossary of terms important to a full understanding of the management options of localized prostate cancer. Screening Tests Clinically localized prostate cancer generally causes no symptoms. Slowing of the urinary stream, arising at night to void, and increased urinary frequency are common symptoms associated with aging but often are unrelated to the presence of prostate cancer. It is for this reason that early detection tests have been developed to identify prostate cancer while it remains confined to the prostate. The two most commonly used tests are a serum PSA level and a DRE.38,39 PSA Prostate specific antigen is a protein produced by cells within the prostate, and in men PSA can be measured in the blood. While higher blood PSA levels often are noted in men with prostate cancer, PSA elevation is not specific for prostate cancer. At present, a higher PSA test value is the most common reason why prostate cancer is detected in the United States. DRE A DRE is an examination by a physician using a gloved finger placed into the rectum to feel the surface of the prostate. The region of the prostate adjacent to the rectal wall is where tumors commonly develop; hard regions or asymmetry may indicate the presence of prostate cancer. Prostate Biopsy Although a higher PSA value or abnormal DRE may raise the suspicion of prostate cancer, detection requires confirmation with a prostate biopsy. At the time of biopsy, several small cores of tissue are removed from the prostate and are then examined by a pathologist to determine if cancer is present. Tumor Characteristics Tumor grade Tumor aggressiveness can be determined by the pathologist’s examination of the microscopic pattern of the cancer cells. The most commonly used tumor grading system is the Gleason grading.40,41 This system assigns a grade for each prostate cancer from 1 (least aggressive) to 5 (most aggressive) based on the degree of architectural differentiation of the tumor. Tumors often show multiple different grade “patterns” within the prostate or even a single core biopsy. To account for this, the Gleason score is obtained by assigning a primary grade to the most predominant grade present and a secondary grade to the second most predominant grade. An exception to this is in the case where the highest (most aggressive) pattern present in a biopsy is not either the most predominant or second most predominant pattern; in this situation, the Gleason score is obtained by combining the most predominant pattern grade with the highest grade. The Gleason score is then displayed as, for example, 3 + 4 where 3 would be the most common pattern of tumor and 4 the second most common pattern (or highest pattern) of tumor seen in the core. Given that the individual Gleason value can range from 1 to 5, the added values (Gleason scores or “sums”) can range from 1 + 1 to 5 + 5 or from 2 to 10. Generally, Gleason scores of 2 to 4 are uncommon; as a result, the majority of detected tumors range from 5 to 10. Occasionally, if a small component of a tumor on prostatectomy is of a pattern that is higher than the two most predominant patterns, then the minor component is added as a tertiary grade to the report (eg 60% pattern 3, 35% pattern 4, and 5% pattern 5 should be reported as 3 + 4 with tertiary grade 5). High-grade cancer With each increase in tumor score (eg from Gleason 5 to 6), there is an increase in tumor aggressiveness. High-grade cancer commonly refers to the most aggressive of tumors, generally Gleason scores of 8 to 10 (the most aggressive group), but also can include Gleason 7 tumors. Tumor stage Tumor stage refers to the degree to which the tumor has involved the prostate gland or has spread. As with other tumors, prostate cancers that involve only a small portion of the prostate are more successfully treated than those that have extended throughout the gland. Similarly, tumors that remain confined to the prostate are also more successfully treated than those that have extended beyond the confines of the gland. Finally, tumors that have spread to sites remote to the prostate (eg metastatic disease in lymph nodes or bone) have the poorest outcomes. The AJCC has established a system of tumor staging (Appendix 4 on-line).42 For the purposes of this guideline, the Panel chose to only examine treatment options for the most common group of patients diagnosed today: the patient whose tumor is confined to the prostate. Using the AJCC nomenclature, these tumors are clinical stage T1 (normal DRE) or T2 (abnormal DRE but no evidence of disease beyond the confines of the prostate), N0 to Nx (no evidence of spread to regional lymph nodes or regional lymph nodes were not assessed), and M0 (no evidence of metastatic spread). Initial Evaluation and Discussion of Treatment Options with the Patient Standard. An assessment of the patient’s life expectancy, overall health status, and tumor characteristics should be undertaken before any treatment decisions can be made. [Based on review of the data and Panel consensus.] Life Expectancy and Health Status Life expectancy, rather than patient age, is a major factor to consider in treatment selection. Thus, the Panel did not specify a chronological age cutoff point for the patient to whom this Guideline applies. When a man’s life expectancy is relatively long, localized prostate cancer can be a cause of morbidity and mortality. At an advanced patient age or when life expectancy is relatively short, competing hazards for mortality reduce the chance that a man will experience disease progression or die from prostate cancer (Appendix 5 on-line).10,43 The patient’s overall health status is the sum of all conditions and includes both patient and family history as well as the present state of the patient’s well-being and the degree of any coexistent disease. There are two reasons to evaluate overall health status prior to deciding on an intervention: (1) overall health status influences life expectancy, and (2) overall health status may affect patient response to adverse events resulting from particular interventions. In the management of prostate cancer, urinary, sexual, and bowel functions are important to consider when choosing a therapy. Tumor Characteristics Tumor characteristics, including PSA level and such changes as velocity and doubling time,44,45 Gleason score, and tumor stage are predictive of cancer outcomes. Using PSA, Gleason score, and tumor stage, risk strata have been defined that are significantly associated with PSA recurrence and cancer specific mortality.46 Therefore, these risk strata have been used as the basis for the current data analysis and treatment option specifications. Because of the differences in outcome by risk group for a given treatment, the Panel opted to develop treatment recommendations based on these risk strata. The size (volume) of the prostate gland may impact the treatment choice in some situations and, thus, requires consideration prior to instituting therapy. Risk Strata Risk stratification schemes have been developed based on the PSA level, biopsy Gleason score, and 2002 AJCC clinical T-category that are associated with the risk of PSA failure and prostate cancer specific mortality following RP, EBRT, or interstitial prostate brachytherapy.47 While variations on this system exist, for the purpose of this report the following scheme was used: • Low risk: PSA ≤10 ng/mL and a Gleason score of 6 or less and clinical stage T1c or T2a • Intermediate risk: PSA >10 to 20 ng/mL or a Gleason score of 7 or clinical stage T2b but not qualifying for high risk • High risk: PSA >20 ng/mL or a Gleason score of 8 to 10 or clinical stage T2c Treatment Options Watchful waiting and active surveillance The great disparity between cancer incidence and mortality indicates that many men may not benefit from definitive treatment of localized prostate cancer. Autopsy studies have shown that 60% to 70% of older men have some areas of cancer within the prostate.48,49 This can be compared with the 15% to 20% of men diagnosed with prostate cancer during their lifetime and with the 3% lifetime risk of death from prostate cancer.36 Men who choose not to undergo immediate therapy may opt for continued followup under a program of WW or active surveillance. Watchful waiting, as studied in RCTs,10,19,50 is based on the premise that some patients will not benefit from definitive treatment of the primary prostate cancer. The decision is made at the outset to forgo definitive treatment and to instead provide palliative treatment for local or metastatic progression if and when it occurs. Options for local palliation could include transurethral resection of the prostate or other procedures for the management of urinary tract obstruction, and hormonal therapy or radiotherapy for palliation of metastatic lesions. In contrast to WW, a program of active surveillance is based on the premise that some, but not all, patients may benefit from treatment of their primary prostate cancer. A program of active surveillance has two goals: (1) to provide definitive treatment for men with localized cancers that are likely to progress and (2) to reduce the risk of treatment-related complications for men with cancers that are not likely to progress. An ideal regimen for active surveillance has not been defined but could include periodic physical examination and PSA testing or periodic repeat prostate biopsies to assess for sampling error of the initial biopsy as well as for subsequent progression of tumor grade and/or volume. Active surveillance currently is under study in non-randomized trials in Canada, the United Kingdom, and the United States.51–53 A multicenter randomized trial of active surveillance vs immediate intervention was to have opened in the United States in 2006. Which patients are suitable candidates for active surveillance? Patients with lower risk tumors (low Gleason score, PSA level, and clinical stage) could be candidates for this treatment strategy. Several studies have shown that patients with lower grade, localized prostate cancer have a low risk for clinical progression within the first 10 to 15 years after the diagnosis.37,51,54–56 Thus, this treatment strategy may be best suited for men with a shorter life expectancy. Generally, patients with high-grade tumors have a relatively poor prognosis and are not suitable for active surveillance but, as will be noted in this report, often have poor outcomes with any therapy. Under special conditions, some patients with a longer life expectancy may opt for active surveillance as their primary management. This may include patients with very small areas of cancer in their biopsy or patients who, at the time of diagnosis, are reluctant to accept the side effects of potentially curative therapies. If the tumor shows evidence of progression (eg increased grade, volume, or stage) while the patient still has a reasonable life expectancy, curative treatments (eg surgery or radiation) can be initiated.53 This can be a difficult clinical decision since signs of progression must be identified before the cancer evolves to a stage (or grade) where therapy is no longer curative. Currently, providing evidence-based recommendations for when to intervene in patients with a long life expectancy are not possible since markers of disease progression are poorly validated. Most reports describe a clinical strategy that includes regular PSA level measurement and DRE with a periodic repeat prostate biopsy along with an option of more active therapy if biochemical (increasing PSA) or tumor grade or progression In this Guideline the Panel used the to to a program initial treatment for the patient with localized cancer. As noted this program and its may be different based on patient and tumor characteristics and is from WW in which a degree of may be used and in which treatment is generally if or symptoms prostate brachytherapy interstitial prostate brachytherapy as a treatment has been since the patients were to the for an open at which time of After the of this were identified by at the Cancer and, in the late a was developed as a definitive treatment for localized prostate Patients with clinically localized prostate cancer are candidates for interstitial prostate brachytherapy, but with to which risk are offered this will use this treatment option for disease only while will both and to a study is to assess prostate and to determine the number of and the isotope, and the for the The are a under of or or with for each Treatment include different in combination with hormonal therapy and/or of the most important factors in predicting the of an is An is defined as one in which or more of the prostate gland at of the radiotherapy radiotherapy has been for the treatment of prostate cancer since the with the radiation at that time Since has been In the late with the first improved the to the of treatment improved the of treatment more of the prostate, and lymph this better of the adjacent to such as the and small The with for the early work in radiation As a of these changes in the 1980s and radiation were increased from the then typical of to to In the the advent of intensity radiotherapy and radiotherapy either with or the of markers treatment The resulting and provide in local tumor and in late For men considering EBRT, the evaluation commonly at a serum PSA level, and biopsy with Gleason the number of positive the number of cores and the presence or of or tertiary grade. staging and is for patients with a Gleason score or a PSA level >20 ng/mL prior to and medical for not present an for a patient radiotherapy is as a curative treatment for prostate cancer in men who not have a history of bowel disease such as disease, or a history of prior The results of RCTs have the use of and or hormonal therapy. As a result, hormonal therapy often is for men with Gleason score 7 cancer or higher or a PSA level in of 10 ng/mL in with can be to to using a conformal radiation and at with a of no more than 10 at the prostatic rectal include a for treatment and either a intensity or radiotherapy using a or For the RCTs a benefit of For patients in the RCTs have shown either hormonal therapy and or to should be For patients with advanced or high-grade disease (Gleason score RCTs have shown two to three years of hormonal therapy to at for years and is common for the assessment of the prostatectomy prostatectomy is a in which the prostate gland and the of the are prostatectomy may be using a or or by using a or on tumor characteristics and the patient’s either or RP is commonly can be with RP and is generally for patients with higher risk of Generally, patients RP will be for one to three after Patients with medical or complications may a longer of Patients are from the with an for one to two to the Because the prostate gland is removed with RP, the major benefit of this is a cancer in patients in whom the prostate cancer is In where the prostate cancer is of a high grade, when the tumor has spread of the prostate or when the tumor is not the prostate may not that all the cancer is the patient at risk for hormonal therapy may be with the of providing of prostate cancer for patients in whom definitive treatment with surgery or radiation is not possible or The of should be from the use of RP or radiation or RP or radiation hormonal therapy. from the a