Active surveillance of lower-risk prostate cancer: a challenge in implementation science
Dr. Catalona conceived the Prostate Cancer Active Surveillance Project (PCASP) in 2016, shortly after the American Urological
Association (AUA) launched its AQUA Registry to assist urologists in complying with the federal government’s requirement for physicians to report their outcomes to receive reimbursement for their services by Medicare and Medicaid. Dr. Catalona believed that if urologists selected to report their results on the uptake and quality of active surveillance (AS) in patients with low-risk prostate cancer, health-services researchers could use the same data stored in the AQUA registry to develop better methods for determining which patients should undergo immediate treatment versus those who could safely adopt AS. He envisioned PCASP as a public-private partnership to enhance “precision care” for prostate cancer patients, possibly at a lower cost to the healthcare system. PCASP has developed into a collaboration that includes many top academic and community practitioners collaborating in the active surveillance arena.
Studies show that it usually takes about 17 years to incorporate new medical advancements into routine medical practice. Examples of this include the smallpox vaccination, penicillin, and insulin. The concept of AS for low-risk prostate cancer first appeared in the literature in England in 1990, and subsequently spread to Canada, the U.S., and around the world. The goal of AS is to avoid the side effects of unnecessarily treating prostate cancer with surgery, radiotherapy, and other methods. The early eligibility criteria for adopting AS were quite stringent; however, in recent years, the indications and intensity of AS have been relaxed. They are considerably dependent upon which doctor you go to or in which region you live. In the U.S., only 50-60% of eligible patients receive AS, as compared with 80% in Sweden. Thus, there remain serious questions about which patients are appropriate and how best to monitor them.
In practice, identifying appropriate candidates for AS is determined by a diagnostic needle biopsy taking samples from diffe
rent regions of the prostate. In about 80% of patients, prostate cancer is multi-focal, i.e., there may be multiple areas of tumors within the prostate that are not always connected. During prostate biopsy procedures, the physician obtains “mapping” biopsies. If the biopsy showscancer, the next considerations are the extent of cancer in the biopsy samples and the aggressiveness of its appearance under the microscope, i.e., the so-called Gleason pattern. In the past, pathologists assigned one Gleason pattern to the most predominant pattern in the tumor and a second Gleason pattern to the second most predominant pattern – for example, “Gleason grades 3 + 4.” The two grade numbers were added together to determine a Gleason score, ranging from 2 to 10. However, Gleason’s original classification, pathologists rarely assign scores 2 to 5; rather, the Gleason scores usually assigned range from 6 to 10, with 6 being the lowest grade. A Gleason score of 6 is considered low grade, a score of 7 is considered intermediate (3+4 is low intermediate, and 4+3 is high intermediate), and a score of 8 to 10 is high-grade prostate cancer.
In 2019, the International Society of Urologic Pathology (ISUP) modified the prostate cancer grading system for diagnosing and managing patients. This modification classifies tumors as 1 out of 5 rather than 6 out of 10. Grade group 1 (GG1 – Gleason pattern 3+3) is called low risk; GG2 (3+4) is called low-intermediate risk; GG3 (4+3) is called high- intermediate risk; and GG4 (4+4) and GG5 (Gleason score of 9 or 10) are called high-risk disease. Patients feel more comfortable choosing AS for the lowest GG1 group.
Because most prostate cancers are multifocal, heterogeneous, and do not all carry the same risk (some progress at different rates), patients legitimately worry because they know complete knowledge about the biological potential of their tumor is lacking. Biopsy cores containing GG1 cancer may harbor genomic features associated with tumors that are likely to increase in grade or already have clinically aggressive behavior, or the biopsy procedure may have failed to sample more aggressive disease elsewhere in the prostate. Studies claiming GG1 cancers can never metastasize or kill come from radical prostatectomy series in which the early removal of the entire prostate gland cured the patients. Long-term follow-up is required to assess the clinical significance of low-grade prostate cancers. To accurately assess the biology of GG1 disease, outcomes with more than 20-year follow-ups of patients never receiving treatment would be required– an impracticable study that is unlikely ever to be undertaken.
Patient education and reassurance is a key element of AS. The patient must feel confident in his prostate cancer management plan. He must comply with the surveillance program, stay engaged, and participate in decision-making regarding his treatment over time. In this regard, a follow-up biopsy (called a confirmatory biopsy) at around 12 months after the initial diagnostic biopsy is another important element. There is some debate about the need for a confirmatory biopsy. Some physicians propose forgoing the second biopsy if MRI scans or genomic testing results suggest that the cancer is not progressing. This is a controversial issue, and some experienced researchers strongly stress the importance of the confirmatory biopsy because in 20% or more of the cases, the confirmatory biopsy will show a higher GG group, more extensive tumor, or both. Therefore, AS includes close monitoring over time, with serial PSA measurements, prostate examinations, periodic biopsies and imaging studies. Clinical researchers are working to improve the quality and outcomes of AS. With 80% of urology care being provided outside academic centers, it is important to develop strategies to implement best- practice guidelines in community and academic practices.
For more information about PCASP see the next article and also: Spring QUEST 2023, pages 8-9, Spring QUEST 2021, pages 8-9 and Summer/Fall 2019, pages 1-2.