Key points

History and evolution of guidelines

The evolution of practice guidelines in medicine has its origin in the early nineteenth century focusing largely on public health measures to control infectious disease epidemics, such as cholera and yellow fever. In the twentieth century, diseases such as tuberculosis and syphilis expanded the role of public health and standardized practices. After World War II, the scope of medicine in the United States and Europe expanded rapidly with the development of new drugs and technology. What started as public health mandates moved into the realm of diagnosis and treatment as new therapies for cancer and tuberculosis were developed, including radium and radiographs; these were recognized as potentially dangerous technologies that required protocols for safe use and delivery.

As screening and early detection of different diseases became more ubiquitous, guidelines began to take on the role of cost containment and quality control. Hospitals were targeted as organizations that could be made more efficient by standardizing practice. With so many different treatment options available, both governments and physician groups attempted to unify management as variation came under suspicion for being deviations from standard of care rather than individual judgment heretofore regarded as the “art of medicine.” Physician groups took on a greater role in guidelines creation in an attempt to maintain physician autonomy.

The American Medical Association played a major role in standardizing medical education, state licensing, and specialty certification in collaboration with specialty societies. The American College of Surgeons began creating uniform standards in surgery by evaluating cancer therapies, standardizing terminology, and publishing results. The American College of Surgeons’ first guidelines were published in 1931 addressing fracture care and organizing cancer services in hospitals. If guidelines development was slow in the early twentieth century, with 20 guidelines in print by 1945 and 35 more by 1974, publication blossomed in the 1980s and was spurred by organizations advocating cost containment and accountability. In 1989 the Agency for Healthcare Research and Quality was established to produce practice guidelines and currently functions as a guidelines clearinghouse.

In the specialty of Urology, the American Urological Association (AUA) created the Practice Guidelines Committee in 1989 to develop evidence-based guidelines that aim to promote the highest standards of urologic care. The first guideline was introduced in 1994 and addressed the topic of benign prostatic hyperplasia. As evidence-based medicine emerged as a guiding force in education and standardization of medical practice, guidelines development processes changed from expert review of literature and synthesis of recommendations to systematic literature reviews and meta-analysis. Many organizations, including the AUA and European Association of Urology (EAU), have adopted grading systems for the strength of evidence and used this to characterize recommendations.

From 2000 to 2005 the AUA made a set of strategic changes in their guidelines process. This new process optimized cost efficiency of the guidelines process, used the Institute of Medicine criteria, and decreased the creation time of new guidelines from a 5-year process to a 2- to 3-year window. In 2008 the current Level of Recommendation system was implemented to link guidelines statements directly to evidence strength. In 2009, in response to rapidly changing evidence that may render existing guidelines obsolete, the AUA created a new program called the Update Literature Review. Every 15 months a methodologist and 3 panel members, 2 from the original guideline and 1 new member, evaluate new literature to determine if a guideline requires updating. AUA guidelines are published on the Agency for Healthcare Research and Quality’s National Guidelines Clearinghouse as well as on the AUA website at auanet.org .

Similarly, the EAU process includes systematic literature review and meta-analysis by a multidisciplinary panel, and grading of evidence based on strength of trial design. Recommendations are based on review of data and panel consensus. Newly published literature is assessed annually to guide future updates.

The National Comprehensive Cancer Center Network guidelines process creates algorithms and decision pathways for management of malignancies based on critical evaluation of current evidence and consensus recommendations by a multidisciplinary panel of experts. Evidence is graded based on the extent, consistency, and quality of data as well as on the level of consensus among the panel and is expressed as categories 1, 2A, 2B, and 3. Uniform consensus requires a majority (85%) of the panel vote. Consensus requires 50% panel vote. The guidelines are continuously reviewed and updated as evidence changes ( www.nccn.org ).

History and evolution of guidelines

The evolution of practice guidelines in medicine has its origin in the early nineteenth century focusing largely on public health measures to control infectious disease epidemics, such as cholera and yellow fever. In the twentieth century, diseases such as tuberculosis and syphilis expanded the role of public health and standardized practices. After World War II, the scope of medicine in the United States and Europe expanded rapidly with the development of new drugs and technology. What started as public health mandates moved into the realm of diagnosis and treatment as new therapies for cancer and tuberculosis were developed, including radium and radiographs; these were recognized as potentially dangerous technologies that required protocols for safe use and delivery.

As screening and early detection of different diseases became more ubiquitous, guidelines began to take on the role of cost containment and quality control. Hospitals were targeted as organizations that could be made more efficient by standardizing practice. With so many different treatment options available, both governments and physician groups attempted to unify management as variation came under suspicion for being deviations from standard of care rather than individual judgment heretofore regarded as the “art of medicine.” Physician groups took on a greater role in guidelines creation in an attempt to maintain physician autonomy.

The American Medical Association played a major role in standardizing medical education, state licensing, and specialty certification in collaboration with specialty societies. The American College of Surgeons began creating uniform standards in surgery by evaluating cancer therapies, standardizing terminology, and publishing results. The American College of Surgeons’ first guidelines were published in 1931 addressing fracture care and organizing cancer services in hospitals. If guidelines development was slow in the early twentieth century, with 20 guidelines in print by 1945 and 35 more by 1974, publication blossomed in the 1980s and was spurred by organizations advocating cost containment and accountability. In 1989 the Agency for Healthcare Research and Quality was established to produce practice guidelines and currently functions as a guidelines clearinghouse.

In the specialty of Urology, the American Urological Association (AUA) created the Practice Guidelines Committee in 1989 to develop evidence-based guidelines that aim to promote the highest standards of urologic care. The first guideline was introduced in 1994 and addressed the topic of benign prostatic hyperplasia. As evidence-based medicine emerged as a guiding force in education and standardization of medical practice, guidelines development processes changed from expert review of literature and synthesis of recommendations to systematic literature reviews and meta-analysis. Many organizations, including the AUA and European Association of Urology (EAU), have adopted grading systems for the strength of evidence and used this to characterize recommendations.

From 2000 to 2005 the AUA made a set of strategic changes in their guidelines process. This new process optimized cost efficiency of the guidelines process, used the Institute of Medicine criteria, and decreased the creation time of new guidelines from a 5-year process to a 2- to 3-year window. In 2008 the current Level of Recommendation system was implemented to link guidelines statements directly to evidence strength. In 2009, in response to rapidly changing evidence that may render existing guidelines obsolete, the AUA created a new program called the Update Literature Review. Every 15 months a methodologist and 3 panel members, 2 from the original guideline and 1 new member, evaluate new literature to determine if a guideline requires updating. AUA guidelines are published on the Agency for Healthcare Research and Quality’s National Guidelines Clearinghouse as well as on the AUA website at auanet.org .

Similarly, the EAU process includes systematic literature review and meta-analysis by a multidisciplinary panel, and grading of evidence based on strength of trial design. Recommendations are based on review of data and panel consensus. Newly published literature is assessed annually to guide future updates.

The National Comprehensive Cancer Center Network guidelines process creates algorithms and decision pathways for management of malignancies based on critical evaluation of current evidence and consensus recommendations by a multidisciplinary panel of experts. Evidence is graded based on the extent, consistency, and quality of data as well as on the level of consensus among the panel and is expressed as categories 1, 2A, 2B, and 3. Uniform consensus requires a majority (85%) of the panel vote. Consensus requires 50% panel vote. The guidelines are continuously reviewed and updated as evidence changes ( www.nccn.org ).

Prostate cancer screening guidelines

In 1990, the debate over prostate cancer screening surrounded the pros and cons of digital rectal examination (DRE). Half of the cases were detected at a locally advanced stage and still there was debate as to whether there was a survival benefit. Later, the incorporation of prostate-specific antigen (PSA) testing into DRE screening was debated and found to increase overall detection dramatically as well as shift the stage of detection to clinically localized disease.

The AUA released its first Best Practice Statement on prostate cancer screening in 2000. At that time, available data showed that one-third of cancers were diagnosed at a locally advanced or metastatic stage and that “a very large proportion of cancers detected through PSA testing are likely to be clinically important, but that PSA testing is unlikely to detect many of the more prevalent small-volume histologic cancers.” Both PSA and DRE were recommended for prostate cancer screening, using a threshold of 4.0 ng/mL, a significant increase in PSA from one test to the next, or an abnormal DRE to prompt consideration of prostate biopsy. The authors recommended a risk-and-benefit discussion with patients and individualization of early detection efforts rather than uniform application of mass screening. Furthermore, testing was recommended to all men age 50 or older with a 10-year life expectancy, and to African American men and those with a family history of prostate cancer in a first-degree relative at an earlier age. This document also addressed the indications for staging tests such as bone scan, PSA kinetics after primary treatment, and PSA behavior in metastatic disease. Methodologically, the Best Practice Policy used literature review, expert opinion, consensus, and peer review.

As the PSA screening era progressed, earlier and more indolent cases were detected and PSA screening came under fire for overdetection and overtreatment of men with prostate cancer. Still, no screening benefit was proven definitively despite attempts at randomized trials to answer this question. In 2009 two trials of prostate cancer screening published interim results with different results in terms of the mortality benefit of screening. The European Randomized Study of Screening for Prostate Cancer (ERSPC) found a 20% reduction in disease-specific mortality in men screened, whereas the Prostate, Lung, Colorectal, and Ovarian (PLCO) trial found no difference. Both trials came under fire for confounding factors and methodological flaws, which could explain results and both were used by various groups to support their screening recommendations. The results of these trials prompted some groups to encourage prostate cancer screening, including the AUA and American Cancer Society, and others to recommend against it, such as the US Preventive Services Task Force.

The AUA Best Practice Statement was updated in 2009, a year that saw great changes in the level of evidence surrounding PSA screening in the United States and Europe. This publication was similar in methodology to the 2000 document and again used literature review, expert opinion, panel consensus, and peer review. It differed in addressing the interval stage migration of prostate cancer with most cases now being diagnosed at a clinically localized stage. Overdiagnosis and overtreatment of indolent disease were addressed and active surveillance was proposed for patients diagnosed in this category. The age for obtaining a first PSA test was decreased to 40 years in all men with at least a 10-year life expectancy. No threshold PSA was recommended to prompt biopsy and a constellation of factors including free and total PSA, ethnicity, family history, size, age, PSA velocity, and comorbidities were suggested for consideration before proceeding with further testing. Although the guidelines were drafted before the publication of the of the ERSPC and PLCO trials, the authors thought that screening was justified in healthy, well-informed men based on the results of the ERSPC trial.

More recently, the AUA Practice Guidelines Committee changed its methodology to a more formalized evidence-based approach, which uses independently contracted teams of methodologists to perform systematic reviews and meta-analysis of the literature as identified by the expert panel. A strength rating was assigned to the evidence supporting each recommendation ranging from A (high) to C (low). The 2013 Early Detection of Prostate Cancer Guideline differed from the prior 2 documents in both methodology and scope. Recommendations were largely based on modeling studies, meta-analysis, and systematic review of available data more heavily than on expert opinion and consensus, and the document focused on only the use of PSA to screen for prostate cancer rather than including posttreatment PSA kinetics or addressing staging studies.

In summary, the Guideline recommended against screening men younger than age 40 and found no data to support routine screening between 40 and 54 for average-risk men. Similar to the 2009 Best Practice Statements, this Guideline recommended individualization of screening decisions for younger men at higher risk due to race and/or family history. The panel recommended screening for men between 55 and 69 years based on the ERSPC trial but advocated shared decision-making due to the high rate of overdiagnosis and overtreatment. A screening interval of 2 years was suggested rather than annual screening to balance risks and benefits of overdiagnosis and false-positive results. As in the 2000 and 2009 Best Practice Statements, the 2013 Guideline recommends against screening men with less than a 10-year life expectancy but also makes a statement against screening men greater than age 70 due to lack of evidence from modeling and the meta-analysis. A caveat to this is that men in excellent health older than age 70 may benefit from screening.

The primary way to diagnose prostate cancer currently is by transrectal or transperineal prostate biopsy. The risks and benefits of prostate biopsy should be discussed with patients before proceeding. The emergence of fluoroquinolone-resistant Escherichia coli has resulted in an increased risk of sepsis from biopsy and is one important possible complication that must be addressed before biopsy. The AUA has published a white paper to provide some guidance regarding periprocedural prophylaxis. Along with the infectious risks, hematuria, hematochezia, hematospermia, dysuria and retention, and pain remain concerns that must be carefully considered and weighed against patient comorbidities.

The EAU Early Detection of Prostate Cancer guideline was also updated and released in 2013. The guideline supports PSA screening due to a decrease in prostate cancer–specific mortality, development of advanced disease, and metastasis. This guideline recommends a baseline PSA between ages 40 and 45 years. PSA screening intervals should be based on the baseline PSA level. All men with a life expectancy of at least 10 years should be offered prostate cancer screening.