Incidence and Cost of Radical Prostatectomy and Radiotherapy for NCCN Low-risk Prostate Cancer in Utah

Prostate cancer incidence has decreased significantly since the early 1990s, associated with decreased prostate cancer screening.^1,2 Population-based prostate cancer screening is currently not recommended due to concerns about overtreatment of nonlethal prostate cancer.² This was demonstrated by two large clinical trials, The Prostate, Lung, Colorectal, and Ovarian cancer screening trial (PLCO) and the European Randomized Study of Screening for Prostate Cancer (ERSPC).  Neither showed any improvement in overall survival with prostate-specific antigen (PSA) screening.^3,4 These studies have increased awareness and subsequent utilization of active surveillance for low-risk prostate cancer, supported by expert consensus guidelines like those of the National Comprehensive Cancer Network (NCCN).^5,6 

Guidelines discourage routine surgical resection or radiotherapy for men with low-risk prostate cancer and can be considered overtreatment. In addition to increased side effects, overtreatment of low-risk prostate cancer is associated with financial toxicity.⁷ In Utah, the two largest health care systems are Intermountain Healthcare (IHC) and University of Utah Health. To evaluate the incidence of overtreatment in Utah compared to national figures, we analyzed the number of men who underwent radical prostatectomy or radiotherapy for low-risk prostate cancer at each institution. We modeled the costs associated with the presumptive overtreatment of men with low-risk disease treated in 2017-2019.

Methods

Data from the Huntsman Cancer Institute (HCI) at the University of Utah and IHC cancer databases from 2017 to 2019 were retrospectively analyzed. Authors extracted data using a standardized form at both institutions. Any discrepancies were reviewed by the first or last author (D.G. or J.T.). Definitive therapy was defined as radical prostatectomy, external beam radiotherapy, or brachytherapy. Men with available pathologic, laboratory, and clinical data who had undergone definitive therapy were stratified by having using the NCCN risk stratification definitions. Patients who could not be risk-stratified due to incomplete or missing data were censored from analysis. Definitive therapy was determined to be appropriate for men with PSA ≥10, clinical stage T2b or greater, ISUP grade group ≥2, and/or ≥50% positive biopsy cores preceding primary treatment. Rates of definitive therapy by year and institution were analyzed. The cost of prostatectomy compared with antigen screening was estimated to be $14,453 from recent work by Trogdon and colleagues.⁷

Results 

Between 2017 and 2019, 1,155 men in Utah underwent radical prostatectomy at the institutions evaluated. Sixty-nine of 1,155 radical prostatectomies (6%) were performed for men with NCCN low-risk prostate cancer (Table 1). At HCI, 1.9%, 6.5%, and 7.7% of radical prostatectomies were for low-risk prostate cancer in 2017, 2018, and 2019 respectively. At IHC, 7.7%, 6.6%, and 5.4% of prostatectomies were for NCCN low-risk prostate cancer. The Financial cost of treating these low-risk men with radical prostatectomies is estimated to be $997,000 ($506,000 at HCI and $491,000 at IHC) over the 3 years studied. Regarding radiotherapy, 8 of 158 (5.1%) patients who were treated with external beam radiotherapy at Huntsman Cancer Institute had NCCN low-risk disease when compared with 7 of 182 (3.8%) at IHC. The costs of external beam radiotherapy to these patients was estimated to be $439,000.⁸

Discussion 

Active surveillance is a safe long-term approach for low-risk prostate cancer, associated with very low cancer-specific mortality.^9,10 Routine radical prostatectomy and external beam radiotherapy for low-risk prostate cancer is currently considered overtreatment and is associated with financial and symptomatic toxicity.1¹ Recent literature reports that while active surveillance is increasing, only 42.1% opted for this strategy.⁵ By age, 35% of men aged ≤55 years and 44% of men aged ≥56 years opted for active surveillance as of 2015.¹² Despite NCCN low-risk prostate cancer accounting for 30.5% of diagnoses between 2010 and 2015, only 12.7% of men were treated with a conservative approach.⁵ In contrast, low-risk prostate cancer accounted for 6% of radical prostatectomies and 4.4% of patients treated with external beam radiation therapy in Utah from 2017-2019. While there are likely some regional variations in treatment patterns, the authors suspect that most of this discrepancy can be explained by the widespread adoption of active surveillance for men with low-risk disease at HCI and IHC. These shifts in management patterns may alter the toxicity profile of population-based prostate cancer screening. For example, when compared with radical prostatectomy, active surveillance is associated with lower rates of erectile dysfunction (45% vs. 80%) and urinary leakage (21% vs. 49%) but more frequent toxicities of tumor progression such as urinary obstruction (44% vs. 28%).¹³ In addition, active surveillance has not been shown to improve patient reported quality of life outcomes.^13,14 Further, As risk stratification improves and overtreatment declines, the harms and benefits of a population-based prostate cancer screening program may need to be reevaluated.

Underdiagnosis of higher grade, clinically significant prostate cancer is frequently cited as a limitation to active surveillance. Data suggest >30% of men will be diagnosed with higher Gleason grade cancer on a subsequent biopsy.^15,16 However, multiple recent strategies can improve diagnostic accuracy. Incorporating fusion magnetic resonance imaging (MRI) with real time ultrasound fusion prostate biopsy has been shown to be a cost-effective approach to reduce pathologic upstaging at the time of prostatectomy.^17,18 Commercially available novel biomarkers can also improve risk stratification. Four kallikrein panel algorithm (4Kpanel) was successful at predicting presence of clinically significant cancer and reclassifying biopsies with Gleason 6 disease to Gleason ≥7.^19,20 Gene expression assays such as Oncotype DX, Prolaris, and Decipher also have been increasingly utilized. Retrospective data suggests that greater utilization of these genomic classifiers may increase physician recommendations for active surveillance.^21-23 However, these novel assays and clinical features may also lead to indications for local treatment of NCCN low-risk prostate cancer.

Using the Decipher test, >10% of men with NCCN low-risk prostate cancer were reclassified into a higher risk clinical-genomic risk group associated with greater risk of metastatic disease and potentially greater benefit from local therapy. Symptoms of tumor progression such as urinary obstruction can be an indication for surgical resection regardless of oncologic risk. In addition, while active surveillance is associated with maintained quality of life and favorable levels of anxiety and depression, certain patients experience a decline in their mental health after opting for conservative management.^24,25 In particular, men with a neurotic personality may be particularly at risk of developing clinically significant anxiety.²⁶ These features and others may lead a physician or patient to prefer local therapies such as radical prostatectomy or external beam radiotherapy over active surveillance. Therefore, not all treatment for NCCN low-risk prostate cancer represents overtreatment. A significant decline in the rates of local therapy for NCCN low-risk disease dose suggest that overtreatment is decreasing with greater understanding of oncologic outcomes. To improve the rates of overtreatment at IHC, a systemwide education program has been implemented.  A research coordinator evaluates the schedules of urologists and radiation oncologists to identify men with low-risk prostate cancer who are considering definitive treatment. Patients are sent a free, interactive patient-friendly video which discusses the role of active surveillance, radical prostatectomy, and radiotherapy for low-risk prostate cancer. Future analysis is planned to evaluate the effectiveness of this educational program. Clinicians at both institutions also are incorporating novel genomic classifiers such as Decipher and Prolaris to identify patients with intermediate risk disease who may benefit from active surveillance.

Strengths of this study include the multi-institution collaboration of both an academic and community-based oncology practice. Combined, University of Utah Health and IHC treat most men with prostate cancer across Utah. In addition, the team was multidisciplinary with medical oncology, radiation oncology, and urologic oncology researchers. Future collaborations are ongoing to increase patient education and reduce overtreatment of prostate cancer. Limitations of this study include the retrospective nature. Also, some data from 2019 had not yet been entered into the IHC cancer registry due to technical limitations. The data are not comprehensive as some patients received workup or treatment outside of the two healthcare systems. 

Conclusion

Approximately 6% of radical prostatectomies and 4.4% of external beam radiotherapy performed in Utah is for men with NCCN low-risk prostate cancer. While these rates are lower than the national average, we estimate nearly $1.5 million in medical costs and toxicities could be deferred had these patients opted for active surveillance. Work is ongoing to characterize clinical toxicity of treatment in these men, and a multi-institutional collaborative education outreach program to reduce overtreatment is in development.

Authors: David Gill, MD¹; Jessica Baumgartner²; Jesse Gygi¹; McKenzie Bell¹; Libby Petersen¹; Bryan Crawford¹; Zoya Sandhu³; Brandon Barney, MD¹; Jonathan Tward, MD²

Affiliations: ¹Intermountain Medical Center. 5121 S Cottonwood St, Murray, UT, USA, 84107 ²University of Utah, Huntsman Cancer Institute, Department of Radiation Oncology. 2000 Cir of Hope Dr #1950, Salt Lake City, UT, USA 84112 ³Rocky Vista University College of Osteopathic Medicine.  255 E Center St, Ivins, UT, USA, 84738

Disclosures: The authors have no disclosures to report.

Address correspondence to:
David Gill, MD Intermountain Medical Center, System Lead of Genitourinary Oncology.
5121 S Cottonwood St, Murray, UT, USA, 84107. 
Email: david.gill@imail.org