Background
Prostate cancer is the second leading cause of cancer death in American men.1 Prostate cancer screening has led to significant decreases in the diagnosis of advanced disease and prostate cancer–specific mortality. However, the cost of the disease has included overdiagnosis of clinically insignificant cancers, and potential for overtreatment with associated unnecessary adverse effects and long-term quality-of-life effects.2 Clinical practice guidelines have been developed by health organizations and oncology societies to facilitate standardized and optimal care for patients. In prostate cancer, these guidelines have aimed to avoid overtreatment of cancers that are unlikely to affect a patient’s life expectancy or quality of life, while identifying those that require treatment and justify the risk of adverse effects. These guidelines, which are updated regularly, provide frameworks for diagnosis and treatment based on the highest quality and most recent evidence.
Compliance with guidelines has been considered a surrogate for quality cancer care and helps to identify gaps and areas for quality improvement.3 The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) provide recommendations based on the best evidence available and on expert consensus. These guidelines are updated annually and revised whenever necessary to reflect new data that may alter clinical practice standards. The NCCN Guidelines remain the most widely used cancer care guidelines in the world. The NCCN Guidelines for Prostate Cancer4 and for Prostate Cancer Early Detection5 provide recommendations for early detection, evaluation, and treatment that seek to avoid overdiagnosis and overtreatment.
Compliance with treatment guidelines has been shown to improve outcomes, decrease morbidity, and decrease the associated cost of care in breast and gastric cancers.6,7 Nevertheless, the effectiveness of guidelines largely depends on dissemination and compliance. Compliance with guidelines varies with cancer type and treatment setting; utilization has been reported to be lower in bladder, testis, and pancreatic cancers, and for lung cancer screening.8–11 In this context, we sought to investigate the impact of an NCCN-compliant multidisciplinary conference on treatment decisions in patients with localized prostate cancer.
Methods
A retrospective review of a prospectively populated quality assurance localized prostate cancer database was performed. All patients with localized prostate cancer who presented to Roswell Park Comprehensive Cancer Center for a second opinion between 2009 and 2019 were identified. All cases were presented to the NCCN Guideline–compliant Localized Prostate Cancer Conference (LPCC) that includes urologists, radiation oncologists, pathologists, and patient advocates.
Data for all patients were reviewed, including demographics, comorbidity-adjusted life expectancy, prostate-specific antigen (PSA) kinetics, PSA density, NCCN risk group, staging scans, and symptom scores (International Prostate Symptom Score [IPSS] and Sexual Health Inventory for Men [SHIM]). LPCC recommendations were based on the NCCN Guidelines. Recommendations included active surveillance/observation, radical prostatectomy, radiotherapy with or without androgen deprivation therapy (ADT), ADT alone, or further workup (eg, staging studies, targeted prostate biopsies, and/or genetic counseling for high-risk patients or those with strong family history). When more than 1 recommendation was given, the favored option by the consensus of the group was considered as the final recommendation. If multiple options were offered with no single favored recommendation, they were reported as either “all options” (if active surveillance, radical prostatectomy or radiotherapy were recommended) or “treatment” (if surgery or radiotherapy were recommended). Other factors that were considered as part of LPCC deliberations included life expectancy, comorbidities, adjusted life expectancy, lower urinary tract symptoms, and erectile function. Outside diagnostic prostate biopsies were reviewed by dedicated genitourinary pathologists for all patients. Discrepancies between outside pathology and the review by genitourinary pathologists were reviewed at LPCC and communicated to outside pathologists. Patients who were presented at LPCC but received treatment outside our hospital were contacted to determine the final treatment received. Concordance between recommendations made by community urologists versus LPCC and with the final treatment received was investigated.
Descriptive statistics were used to summarize the data. Categorical variables were compared using Fisher exact test and continuous variables by Wilcoxon rank sum test. Multivariable stepwise logistic regression with forward selection models were fit to evaluate variables associated with concordance between community recommendations, LPCC recommendations, and treatment received. Variables included age, body mass index (BMI), Charlson comorbidity index (CCI), race, prostate volume, Gleason grade, number of biopsy cores, number of positive cores, cT stage, NCCN risk group, PSA level, PSA density, LPCC era, and SHIM and IPSS scores at diagnosis. Cochran-Armitage trend test was used to evaluate trends in concordance over time. Statistical significance was defined as P≤.05. All tests were double-sided. SAS 9.4 (SAS Institute) was used for all analyses.
Results
Patient Characteristics
A total of 1,164 patients were included (supplemental eFigure 1, available with this article at JNCCN.org). Mean [SD] age was 64 [8] years, median PSA level was 5.7 ng/mL (interquartile range [IQR], 4.1–8.1), median PSA doubling time was 4.7 years (IQR, 3.2–7.0), and median PSA density was 0.16 ng/mL2 (IQR, 0.10–0.25). NCCN risk group distributions were 26% very low/low risk, 27% favorable intermediate risk, 25% unfavorable intermediate risk, and 22% high/very high risk. Upon pathology review, change in pathology occurred in 11%, which resulted in NCCN risk group reclassification in 9% of patients (supplemental eTables 1 and 2).
Treatment Recommendations
Concordance between community and LPCC recommendations occurred in 78% of patients. Concordance increased over time, from 65% in 2009 to 86% in 2019 (P<.01) (supplemental eFigure 2). The highest agreement was for radical prostatectomy (89%). Lowest agreements occurred for ADT monotherapy (21%) followed by radiotherapy (53%) (Figure 1).
Concordance between community and LPCC recommendations.
Abbreviations: ADT, androgen deprivation therapy; AS, active surveillance; LPCC, Localized Prostate Cancer Conference; RP, radical prostatectomy; RT, radiotherapy.
aADT was recommended to only 24 patients by community urologists. LPCC concordance was 21%; the remaining LPCC recommendations were RT (42%), AS (25%), RP (8%), and RP or RT (4%).
Citation: Journal of the National Comprehensive Cancer Network 21, 4; 10.6004/jnccn.2022.7090
Treatment Received
Concordance between community recommendations and treatment received occurred in 65% overall. Concordance increased from 59% in 2009 to 70% in 2019, but the difference over time did not reach statistical significance (P=.08) (supplemental eFigure 2). Agreement was highest for active surveillance (80%) and lowest for radiotherapy; among patients for whom radiotherapy was recommended as the preferred option by the community, 26% received radiotherapy, 39% elected active surveillance, and 32% received radical prostatectomy (Figure 2 and Table 1). On the other hand, concordance between LPCC recommendations and treatment received occurred in 92%. Concordance increased over time from 89% in 2009 to 94% in 2019, but did not reach statistical significance (P=.24) (supplemental eFigure 2). Agreement was 95% for active surveillance, 93% for radical prostatectomy, and 80% for radiotherapy (Figure 2 and Table 1). Stratified by NCCN risk groups, 83% of patients with very low-/low-risk disease and 50% with favorable intermediate-risk disease who were recommended radiotherapy in the community ultimately ended up receiving active surveillance instead (supplemental eFigure 3). This was observed to a much lesser extent for radical prostatectomy, where 40% of patients with very low-/low-risk disease and 24% with favorable intermediate-risk disease who were offered radical prostatectomy in the community ended up receiving active surveillance.
Concordance between community and LPCC recommendations and treatment received.
Abbreviations: ADT, androgen deprivation therapy; AS, active surveillance; LPCC, Localized Prostate Cancer Conference; RP, radical prostatectomy; RT, radiotherapy.
aADT was recommended to only 18 patients by community urologists (22% received ADT, 56% received RT, 11% received AS, and 11% received RP) and 9 patients by LPCC (89% received ADT and 11% received RT).
Citation: Journal of the National Comprehensive Cancer Network 21, 4; 10.6004/jnccn.2022.7090
Comparison of Community and LPCC Recommendations and Treatment Received
On multivariable analysis, more recent LPCC era (OR, 2.77; 95% CI, 1.45–5.30; P<.01), higher CCI (OR, 0.74; 95% CI, 0.59–0.93; P=.01), higher BMI (OR, 0.76; 95% CI, 0.61–0.95; P=.02), very low/low NCCN risk group (OR, 0.41; 95% CI, 0.23–0.74; P<.01), larger prostate volume (OR, 0.94; 95% CI, 0.89–0.99; P=.02), and higher SHIM score (OR, 1.20; 95% CI, 1.02–1.42; P=.03) were associated with concordance between community and LPCC recommendations and treatment received (Table 2).
Multivariable Analysis Modeling Variables Associated With Concordance Between Community and LPCC Recommendations and Treatment Received
Discussion
Ensuring quality cancer care is of utmost importance for both patients and healthcare systems. The Institute of Medicine highlighted the importance of developing guidelines for prevention, diagnosis, treatment, and palliation of cancer, and to monitor the quality of cancer care.12,13 Compliance with cancer guidelines for melanoma, pancreatic, and ovarian cancers has been associated with improved outcomes.14–16 The Centers for Medicare & Medicaid Services use “pay for performance” as a means for providing economic incentives for providing high-quality, guideline-compliant care.17,18 However, noncompliance remains a significant problem. Variables such as older age, single marital status, female gender, high tumor stage, and severe comorbidity were associated with guideline-noncompliant recommendations.14,19
In the current study, concordance between the recommendation provided by the community urologist and by the guideline-compliant multidisciplinary team (LPCC) occurred in 78% of patients, and this concordance seemed to increase over time, reaching 86% in 2019. Concordance between the community recommendation and the final treatment received occurred in 65% of patients compared with 92% for the LPCC recommendation. Many different factors can affect patients’ treatment decisions for prostate cancer, including recommendations from their treating physician(s), disease aggressiveness, whether monitoring is preferable to definitive treatment, cost, time required for treatment, potential adverse effects (eg, urinary, bowel, and sexual dysfunction), current symptoms (eg, lower urinary tract symptoms), and individual characteristics (eg, age, race/ethnic group, and highest educational level). The physician’s recommendation has been reported to have the most influence on a patient’s decision.20,21 A multidisciplinary group can help minimize bias from treatment modality preference and financial incentives and thereby facilitate shared decision-making.22,23
The highest discordance between community recommendations and treatment received was for radiotherapy, where only 26% of patients who were recommended radiotherapy by the community urologist received it. On the other hand, 80% of patients who were recommended radiotherapy by the LPCC received it. When stratified by NCCN risk groups, 83% of patients with very low-/low-risk disease and 50% with favorable intermediate-risk disease to whom radiotherapy was recommended in the community received active surveillance instead. Although still considered guideline-compliant, this supports our observation that many candidates for active surveillance are recommended radiotherapy in the community. This was observed to a much lesser extent for radical prostatectomy, where 40% of patients with very low-/low-risk disease and 24% with favorable intermediate-risk disease who were offered radical prostatectomy in the community ended up receiving active surveillance. An increasing number of urologists, especially in private practice, incorporated intensity-modulated radiotherapy (IMRT) into their practice by adding a radiation oncologist to the group.24–26 Another study compared the use of IMRT and other management options for prostate cancer treated by urologists at 11 NCCN Member Institutions versus 11 matched self-referring urology practices before and after ownership of IMRT. The rate of IMRT use by self-referring urologists increased from 9% to 42%, active surveillance decreased by 6%, and the use of prostatectomy and other procedures declined by <4%. On the other hand, there was no significant change in the practice patterns of urologists employed by NCCN Member Institutions, where approximately 8% underwent IMRT.22 Another possibility is that patients with relatively higher surgical complexity (such as those with previous pelvic or inguinal surgeries, or transurethral resection of the prostate) may be deemed less favorable surgical candidates and therefore offered radiotherapy more frequently in the community.27 In contrast, they may not be considered as such in high-volume designated cancer centers and are still offered radical prostatectomy.
In the current study, pathology for all patients was reviewed by dedicated genitourinary pathologists. Discrepancies were noted in only 11% of patients and resulted in disease reclassification in 9%. The Gleason scoring system is crucial for risk stratification that is central to prognosis assessment and overall management. However, Gleason score assignment may be affected by subjectivity and interobserver variation, which depend on the experience and degree of specialization of the pathologist.28 Interobserver agreement varies from 10% to 72%.28–31 Centralized review may change the Gleason score, with subsequent change in risk stratification and important implications on treatment decisions.32 One study reported changes in Gleason score in 28% of cases upon second review.31
We investigated the variables associated with concordance between community and LPCC recommendations and treatment received. Patients with prostate cancer in the very low/low NCCN risk group, in whom active surveillance is usually the preferred option, were less likely to demonstrate concordance. Many of these patients were offered radiotherapy in the community. In 2021, the NCCN Guidelines changed the recommendation regarding active surveillance for low-risk prostate cancer, no longer listing active surveillance as the “preferred” management option for patients with low-risk prostate cancer and a life expectancy of ≥10 years, which raised concerns about overtreatment among the urologic community. In 2022, the NCCN Prostate Cancer Panel extensively revised the “Principles of Active Surveillance and Observation” to provide detailed guidance on important aspects of this management approach and changed the recommendation for active surveillance in patients with low-risk prostate cancer to “preferred for most patients.”4 The panel also acknowledged the heterogeneity across the low-risk disease group and that some factors may be associated with an increased probability of near-term risk of disease progression, including high PSA density, high number of positive cores (≥3), known BRCA2 germline mutations, and others. Combining multiparametric MRI and other markers may help with risk stratification, but their value remains uncertain. Treatment with radical prostatectomy or radiotherapy are still options that can be undertaken after careful counseling and shared decision-making.
This study is not without limitations. First, the retrospective study design has its inherent limitations. Second, patients who were treated outside of our institution were contacted to determine the treatment received. This may have brought some pain and distress for patients. Some of the patients or the next of kin refused to participate in the study, and therefore their data were excluded. Third, no data were collected on regret about treatment decision. Fourth, when more than 1 option was recommended by the guidelines, the LPCC panel incorporated all relevant data (eg, positive family history, presence of lower urinary tract symptoms) to determine a “preferred” option for the patient. Therefore, discordance in recommendation between the community and the LPCC does not necessarily imply that the community recommendation was not compliant with NCCN Guidelines. Additionally, concordance with one recommendation over the other may reflect where patients received their final treatment. This may also have introduced selection bias as well. Finally, it is not known whether the community recommendations were made by a formal multidisciplinary process or by referral to another provider within the same group.
Conclusions
Community recommendations differed from the multidisciplinary NCCN-compliant recommendations in 22% of patients, primarily for radiotherapy. Multidisciplinary recommendations matched the treatment received in 92% of patients compared with 65% for community recommendations.
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