Trends in Active Surveillance for Men With Intermediate-Risk Prostate Cancer

Key Points Question What clinical factors and sociodemographic patient characteristics are associated with utilization of active surveillance for the primary management of intermediate-risk prostate cancer? Findings In this cohort study using data from 289 584 patients identified in the National Cancer Database, the utilization of active surveillance as initial management strategy for patients newly diagnosed with intermediate-risk prostate cancer has increased over time. On multivariable analysis, the use of active surveillance was associated with increased age, lower Gleason score, early T stage, treatment at an academic center, higher level of education, government provided insurance type, closer proximity to treatment facility, regional facility location, and lower income. Meaning Our findings suggest active surveillance utilization is increasing over time with key clinical and sociodemographic factors associated with this management strategy.


Introduction
In 2023, prostate cancer remains a significant health burden, with an estimated 288 300 new cases and 34 700 deaths in the US. 1 For men with a new diagnosis, optimal treatment management depends on a variety of factors related to patients' age, prostate-specific antigen (PSA) levels, tumor stage, and pathology from standardized multicore biopsy.Risk stratification systems, including those published in Nation Comprehensive Cancer Network (NCCN) guidelines, stratify patients based on these patient oncologic characteristics, with management options tailored to a patient's estimated life expectancy. 2Current NCCN recommendations allow for active surveillance or definitive management with surgery or radiation for patients with favorable intermediate risk prostate cancer, with similar recommendations-sans active surveillance and with or without androgen deprivation therapy (ADT) intensification-for those with unfavorable risk disease.Data from several prospective trials including PIVOT and UK ProtecT demonstrate comparably low prostate cancer-specific mortality for patients with low risk disease, or those diagnosed by PSA screening, randomized to active treatment with prostatectomy, radiation therapy, or observation at initial prostate cancer diagnosis. 3,4Active surveillance is the preferred strategy for men with low-risk prostate cancer, and use of this strategy has increased over time. 5With the inclusion of an additional 4 years of data, this study is an update of our prior research reexamining national trends in implementation of active surveillance as an initial treatment strategy in men with intermediate-risk prostate cancer. 6

Data Source
The National Cancer Database (NCDB) is a joint project of the Commission on Cancer (CoC) of the American College of Surgeons and the American Cancer Society.The NCDB tabulates longitudinal data from more than 70% of all new cancer diagnoses on an annual basis, encompassing more than 1500 hospitals across all 50 states.From 2010 to 2020, men undergoing active surveillance were reported to the NCDB and coded within the variable RX_SUMM_TREATMENT_STATUS.The collected data include cancer characteristics, primary and adjuvant management, and long-term outcomes, as well as self-reported patient demographic information such as age, sex, race, educational level, income, insurance status, Charlson-Deyo comorbidity score, facility type, distance from facility, and facility geographic region.As this study used deidentified data from the NCDB, the requirement for formal institutional review and the need for informed patient consent were waived, consistent with the policies of Weill Cornell Medicine.The CoC's NCDB and the hospitals participating in the NCDB are the source of the deidentified data used herein; they have not verified and are not responsible for the statistical validity of the data analysis or the conclusions derived by the authors.This report follows the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline for cohort studies.

Active Surveillance Patient Selection
Only men coded for active surveillance (ie, RX_SUMM_TREATMENT_STATUS) were considered to have undergone active surveillance.Men who did not receive any primary therapy (radiation or surgery) were not considered to have undergone active surveillance.Duration of active surveillance or details of any subsequent treatment were not available for analysis.

Statistical Analysis
Descriptive statistics for factors of interest were reported as frequency.The Cochran-Armitage test was used to identify significant trends in active surveillance or intervention (prostatectomy or radiotherapy).Multivariable logistic regression was performed to examine demographic, clinical, and socioeconomic factors associated with active surveillance or intervention.The logistic regression was adequate to discriminate whether the patient got active surveillance (area under the curve = 0.815).
Analysis was performed on the entire cohort as well as for favorable and unfavorable intermediate risk subgroups.All tests were 2-sided and considered significant at a level of P < .05.All analyses were performed using SAS software, version 9.4 (SAS Institute).Analysis was performed in September 2023.

Discussion
Using a national hospital-based, oncology-focused database cohort of patients newly diagnosed with prostate cancer, we show active surveillance utilization is increasing over time in those with intermediate risk disease, consistent with our prior analysis. 6 The 2023 15-year follow-up publication from the UK ProtecT study shows comparable, noninferior prostate cancer-specific mortality between patients randomized to prostatectomy, definitive radiation or observation suggesting the safety and practicality of active surveillance for patients with newly diagnosed, organ-confined prostate cancer. 4Even though 61% of men originally assigned to active surveillance had moved to radical treatment and the fact that there were higher rates of metastasis in the observation arm, these factors did not portend a statistically worse overall outcome between the arms examined in the study.Furthermore, there are a portion of patients  Advances in imaging including the integral role of multiparametric magnetic resonance imaging (MRI) has allowed for more accurate targeting of potentially significant prostate cancer and monitoring of patients on active surveillance. 9There are recent studies suggesting prostate-specific membrane antigen PET/CT combined with mpMRI allows for improved negative predictive value and sensitivity for clinically significant prostate cancer in an MRI-triaged population thus potentially reducing need for prostate biopsies for some patients.

Limitations
Limitations of this study include those associated with its retrospective nature and analysis of a dataset that includes information from a national hospital-based registry.As such, this is not a population-based cohort and there is a possibility that the numbers reported based on this dataset do not accurately or precisely reflect the entirety of patients with newly diagnosed prostate cancer in the US.Furthermore, the database collects only the initial treatment course of the patients and does not account for subsequent treatment decisions or information.For instance, a patient recommended to undergo active surveillance and coded as such may ultimately proceed with alternative treatment at their discretion, which would not be included or represented in the data available for analysis.

Conclusions
In this cohort study of patients with intermediate-risk prostate cancer diagnosed from 2010 to 2020, we provided an updated analysis highlighting the increasing implementation of active surveillance as an initial treatment approach.Furthermore, our subset analysis shows this is particularly evident for those considered to be favorable intermediate risk.Prospective data with improved risk stratification incorporating genomics as well as novel surveillance strategies may continue to better delineate ideal or optimal candidates for this treatment approach thereby doing less harm while continuing to treat a deadly disease.

Findings
In this cohort study using data from 289 584 patients identified in the National Cancer Database, the utilization of active surveillance as initial management strategy for patients newly diagnosed with intermediate-risk prostate cancer has increased over time.On multivariable analysis, the use of active surveillance was associated with increased age, lower Gleason score, early T stage, treatment at an academic center, higher level of education, government provided insurance type, closer proximity to treatment facility, regional facility location, and lower income.Meaning Our findings suggest active surveillance utilization is increasing over time with key clinical and sociodemographic factors associated with this management strategy.

Figure .
Figure.Trends in Active Surveillance (AS) Utilization as Initial Treatment Strategy for Patients With Intermediate-Risk Prostate CancerIntermediate risk patients with prostate cancer A 2rends in Active Surveillance for Men With Intermediate-Risk Prostate Cancer Men with intermediate-risk prostate cancer coded for active surveillance, surgery, or radiotherapy as the initial treatment strategy from 2010 to 2020 were included in this study (eFigure in Supplement 1).All risk groups referenced in this study are based on NCCN guidelines accessed during analysis.2Menclassified as low risk or high risk for prostate cancer were excluded from analysis.

Table 1 .
Patient Demographics (continued) a Other includes American Indian, Aleutian or Eskimo, Our results suggest that approximately 8.6% of patients with intermediate-risk prostate cancer elected for active surveillance as their primary management strategy in 2020, with a preponderance of those with favorable intermediate risk comprising this group.This rate has increased significantly compared with 2.0% of men in 2010, but remains lower than rates recorded in other countries.According to the National Prostate Cancer Register of Sweden (NPCR), in 2022, 17% of intermediate-risk cases underwent active surveillance.Our updated analysis highlights several predictable and previously reported cancer and patient specific factors associated with patients undergoing active surveillance.These factors include increased patient age, grade group 1 or 2 pathology, and earlier T stage.Our data highlights that most patients undergoing active surveillance have a low Charlson-Deyo comorbidity score and that the decision regarding definitive treatment or active surveillance is not driven by poor performance status.Our analysis also highlights independent socioeconomic and demographic factors such as government insurance or lack of insurance, treatment at academic institutions, treatment at facilities located in New England, lower income, non-White race, patient proximity to treatment location, and patient residence in rural areas or areas with lower high school completion percentage as independent factors that affect the odds of patients receiving active surveillance.How these demographic and socioeconomic factors may affect active surveillance implementation, patient selection, and treatment discussions between clinicians and patients is worth consideration, although out of scope of this article.

Table 2 .
7ultivariable AnalysisDownloaded from jamanetwork.combyguest on 09/20/2024 randomized to the observation arm who are still alive and have yet to receive any treatment for their cancer and have thus far avoided morbidity associated with definitive treatment.However, several of the patients randomized to the observation arm died from their cancer, necessitating caution with blanket recommendations for surveillance for all comers.Additional data points beyond PSA, Gleason score or pathology, physical examination, and age might be necessary to better characterize and predict which patients would benefit from definitive treatment and what level of treatment intensification or deintensification may lead to superior outcomes.How underlying genomic risk may play a role is yet to be solidified for patients considering active surveillance, although studies suggest implementation of available genomic tests may better risk stratify patients and inform decision making.7Thereare 2 large randomized NRG clinical trials 10Whether prostate-specific membrane antigen PET/CT can be implemented for monitoring patients on active surveillance is of interest,