Overtreatment Of Low-risk Prostate Cancer Research Articles

Time Trends and Variation in the Use of Active Surveillance for Management of Low-risk Prostate Cancer in the US

Active surveillance (AS) is endorsed by clinical guidelines as the preferred management strategy for low-risk prostate cancer, but its use in contemporary clinical practice remains incompletely defined. To characterize trends over time and practice- and practitioner-level variation in the use of AS in a large, national disease registry. This retrospective analysis of a prospective cohort study included men with low-risk prostate cancer, defined as prostate-specific antigen (PSA) less than 10 ng/mL, Gleason grade group 1, and clinical stage T1c or T2a, newly diagnosed between January 1, 2014, and June 1, 2021. Patients were identified in the American Urological Association (AUA) Quality (AQUA) Registry, a large quality reporting registry including data from 1945 urology practitioners at 349 practices across 48 US states and territories, comprising more than 8.5 million unique patients. Data are collected automatically from electronic health record systems at participating practices. Exposures of interest included patient age, race, and PSA level, as well as urology practice and individual urology practitioners. The outcome of interest was the use of AS as primary treatment. Treatment was determined through analysis of electronic health record structured and unstructured clinical data and determination of surveillance based on follow-up testing with at least 1 PSA level remaining greater than 1.0 ng/mL. A total of 20 809 patients in AQUA were diagnosed with low-risk prostate cancer and had known primary treatment. The median age was 65 (IQR, 59-70) years; 31 (0.1%) were American Indian or Alaska Native; 148 (0.7%) were Asian or Pacific Islander; 1855 (8.9%) were Black; 8351 (40.1%) were White; 169 (0.8%) were of other race or ethnicity; and 10 255 (49.3%) were missing information on race or ethnicity. Rates of AS increased sharply and consistently from 26.5% in 2014 to 59.6% in 2021. However, use of AS varied from 4.0% to 78.0% at the urology practice level and from 0% to 100% at the practitioner level. On multivariable analysis, year of diagnosis was the variable most strongly associated with AS; age, race, and PSA value at diagnosis were all also associated with odds of surveillance. This cohort study of AS rates in the AQUA Registry found that national, community-based rates of AS have increased but remain suboptimal, and wide variation persists across practices and practitioners. Continued progress on this critical quality indicator is essential to minimize overtreatment of low-risk prostate cancer and by extension to improve the benefit-to-harm ratio of national prostate cancer early detection efforts.

Indication for Active Surveillance in the Era of MRI-Targeted Prostate Biopsies

Introduction: Active surveillance (AS) strategies were established to avoid overtreatment of low-risk prostate cancer (PCa) patients. Low tumor volume represents one indication criteria; however, applying this criterion after MRI-targeted prostate biopsies may lead to overestimation of tumor volume; wherefore, patients suitable for AS would be exposed to the risk of overtreatment. Methods: This retrospective analysis included 318 patients in which PCa was detected by MRI-TRUS fusion prostate biopsy. Classic and extended indication for AS included Gleason 6 and Gleason 3 + 4 cancer, respectively. We assessed the effect of targeted biopsies and temporary rating strategies on eligibility for AS and developed new “composite” algorithms to more accurately assess eligibility for AS. Results: Forty-four (13.8%) and 60 (18.9%) of the 318 patients qualified for AS according to “classic” and “extended” criteria, respectively. Application of the “composite 1” definition led to AS eligibility of 52 of 248 patients (20.97%) in the classic and of 77 of 248 patients (31.05%) in the “extended” group. Conclusions: We could demonstrate that classic algorithms led to ineligibility of patients for AS. We propose a new rating algorithm to improve tumor assessment for a more accurate indication for AS.

Cause of Mortality after Radical Prostatectomy and the Impact of Comorbidity in Men with Prostate Cancer: A Multi-institutional Study in Korea.

PurposeThis study aimed to examine the causes of death in Korean patients who underwent radical prostatectomy for prostate cancer and investigate the relationship between comorbidity and mortality.Materials and MethodsWe conducted a retrospective multicenter cohort study including 4,064 consecutive patients who had prostate cancer and underwent radical prostatectomy between January 1998 and June 2013. The primary endpoint of this study was all-cause mortality, and the secondary endpoints were cancer-specific mortality (CSM) and other-cause mortality (OCM). Charlson comorbidity index (CCI) was calculated to assess the comorbidities of each patient.ResultsOf 4,064 patients, 446 (11.0%) died during follow-up. The cause of death was prostate cancer in 132 patients (29.6%), other cancers in 121 patients (27.1%), and vascular disease in 57 patients (12.8%) in our cohort. The overall 10-year CSM rate was lower than the OCM rate (4.6% vs. 10.5%). The 10-year CSM rate was lower than the OCM rate in low- to intermediate-risk group patients (1.2% vs. 10.6%), whereas they were similar in high-risk group patients (11.8% vs. 10.1%). In the multivariable analysis, CCI was independently associated with all-cause mortality after radical prostatectomy, regardless of age and pathologic features.ConclusionDeath from prostate cancer was rare in Korean men who underwent radical prostatectomy. Clinicians should be aware of the possibility of overtreatment of low-risk prostate cancer in men with significant comorbidity. Our findings may help to facilitate counseling and plan management in this patient group.

Contemporary trends in treatment for low-risk prostate cancer.

5082 Background: Active surveillance (AS) is the preferred management of low risk (LR) prostate cancer (PCa) to decrease morbidity associated with overtreatment. We hypothesized management trends would show AS increasing and initial definitive treatment decreasing for men with LR PCa. This study describes contemporary trends in initial treatment for LR PCa using the National Cancer Database (NCDB), which includes ~50% of new PCa diagnoses in the United States per year. Methods: NCDB was queried for all patients with LR localized PCa (2010-2015), defined as non-metastatic PCa with PSA<10 ng/mL, Gleason ≤6 and clinical T1-T2a primary tumor. Staging was assigned using 2018 American Joint Committee on Cancer guidelines. Patients refusing treatment, unable to be treated due to comorbidity or with unknown treatment status were excluded. Men were grouped based on NCDB codes for initial treatment including prostatectomy (PR), radiation (RT), AS and no treatment. Those receiving initial definitive treatment were compared to those who were not using logistic regression. Multivariable analysis was conducted for factors possibly correlating with management choice. Results: Of the 645,932 patients identified, 134,540 met inclusion criteria. Of these patients, 114,183 (84.9%) underwent PR or RT compared to 20,357 (15.1%) that did not. When examined over time, 92.4% of patients underwent initial PR or RT in 2010 vs. 73.9% in 2015 (p<0.001). 90% of patients seen at community cancer centers underwent definitive initial treatment compared to 78% of those seen at academic centers (p<0.001). Conclusions: In this national, hospital-based cohort overall rates of definitive initial treatment for LR PCa remain high, though seem to be decreasing over time. Overtreatment of LR PCa remains a concern and illustrates the relatively slow incorporation of guideline recommendations into clinical practice at the national level. [Table: see text]

Value of Serial Multiparametric Magnetic Resonance Imaging and Magnetic Resonance Imaging–guided Biopsies in Men with Low-risk Prostate Cancer on Active Surveillance After 1 Yr Follow-up

BackgroundActive surveillance (AS) aims to reduce overtreatment of low-risk prostate cancer (PC). Incorporating multiparametric magnetic resonance imaging (mp-MRI) and MR-guided biopsy (MRGB) in an AS protocol might contribute to more accurate identification of AS candidates. ObjectiveTo evaluate the value of 3T mp-MRI and MRGB in PC patients on AS at inclusion and after 12-mo follow-up. Design, setting, and participantsPatients with cT1c–cT2 PC, prostate-specific antigen (PSA) ≤10ng/ml, PSA density <0.2ng/ml/ml, and Gleason scores (GSs) of ≤6 and ≤2 positive biopsy cores were included and followed in an AS protocol including mp-MRI and MRGB. The mp-MRI and MRGB were performed at <3 and 12 mo after diagnosis. Reclassification was defined as GS >6, >2 positive cores at repeat transrectal ultrasound-guided biopsy (TRUSGB), presence of PC in >3 separate cancer foci upon both MRGB and TRUSGB, or cT3 tumor on mp-MRI. Outcome measurements and statistical analysisReclassification rates, treatment after discontinuation, and outcome on radical prostatectomy after discontinuing AS were reported. Uni- and multivariate analyses were performed to identify predictors of reclassification after 1 yr. Results and limitationsFrom 2009 to 2013, a total of 111 of 158 patients were consecutively and prospectively included. Around initial diagnosis, 36 patients were excluded from the study protocol; mp-MRI+MRGB reclassified 25/111 (23%) patients, and 11 patients were excluded at own request. Reasons for reclassification were as follows: GS upgrade (15/25, 60%); cT3 disease (3/25, 12%); suspicion of bone metastases (1/25, 4%); and multifocal disease upon MRGB (6/25, 24%). Repeat examinations after 1 yr showed reclassification in 33/75 patients (44%). Reasons were the following: GS upgrade upon TRUSGB (9/33, 27%); volume progression upon TRUSGB (9/33, 27%); cT3 disease upon mp-MRI (1/33, 3%); GS upgrade upon MRGB (1/33, 3%); volume progression upon MRGB (1/33, 3%); multifocal disease upon MRGB (2/33, 6%); and upgrade or upstage upon both TRUSGB and MRGB (10/33, 30%). On logistic regression analysis, the presence of cancer at initial mp-MRI and MRGB examinations was the only predictor of reclassification after 1 yr (odds ratio 5.9, 95% confidence interval 2.0–17.6). ConclusionsAlthough mp-MRI and MRGB are of additional value in the evaluation of PC patients on AS, the value of mp-MRI after 1 yr was limited. As a considerable percentage of GS ≥7 PC after 1 yr was detected only by TRUSGB, TRUSGB cannot be omitted yet. Patient summaryMore aggressive tumors are detected if low-risk prostate cancer patients are additionally monitored by magnetic resonance imaging. However, some high-grade tumors are detected only by transrectal ultrasound-guided biopsy.

Treatment Preferences for Active Surveillance versus Active Treatment among Men with Low-Risk Prostate Cancer.

Due to the concerns about the overtreatment of low-risk prostate cancer, active surveillance (AS) is now a recommended alternative to the active treatments (AT) of surgery and radiotherapy. However, AS is not widely utilized, partially due to psychological and decision-making factors associated with treatment preferences. In a longitudinal cohort study, we conducted pretreatment telephone interviews (N = 1,140, 69.3% participation) with newly diagnosed, low-risk prostate cancer patients (PSA ≤ 10, Gleason ≤ 6) from Kaiser Permanente Northern California. We assessed psychological and decision-making variables, and treatment preference [AS, AT, and No Preference (NP)]. Men were 61.5 (SD, 7.3) years old, 24 days (median) after diagnosis, and 81.1% white. Treatment preferences were: 39.3% AS, 30.9% AT, and 29.7% NP. Multinomial logistic regression revealed that men preferring AS (vs. AT) were older (OR, 1.64; CI, 1.07-2.51), more educated (OR, 2.05; CI, 1.12-3.74), had greater prostate cancer knowledge (OR, 1.77; CI, 1.43-2.18) and greater awareness of having low-risk cancer (OR, 3.97; CI, 1.96-8.06), but also were less certain about their treatment preference (OR, 0.57; CI, 0.41-0.8), had greater prostate cancer anxiety (OR, 1.22; CI, 1.003-1.48), and preferred a shared treatment decision (OR, 2.34; CI, 1.37-3.99). Similarly, men preferring NP (vs. AT) were less certain about treatment preference, preferred a shared decision, and had greater knowledge. Although a substantial proportion of men preferred AS, this was associated with anxiety and uncertainty, suggesting that this may be a difficult choice. Increasing the appropriate use of AS for low-risk prostate cancer will require additional reassurance and information, and reaching men almost immediately after diagnosis while the decision-making is ongoing. Cancer Epidemiol Biomarkers Prev; 25(8); 1240-50. ©2016 AACR.

Ageism Defies Clinical Data

“The study by Bekelman et al has important implications, given that it highlights the prevalent age bias against the use of RT in elderly men with high-risk prostate cancer. Much of the public discourse relating to prostate cancer emphasizes the overtreatment of low-risk prostate cancer in men who are least likely to die as a result of prostate cancer. Nevertheless, given the weight of evidence favoring the addition of RT to androgen-deprivation therapy for high-risk disease, one must question why, in the population analyzed by Dr. Bekelman and his associates, 49% of men older than age 65 years with locally advanced or high-risk prostate cancer were treated with ADT monotherapy, a rate that increased to 61% in those aged 75 years or older. In elderly men who are sufficiently healthy to tolerate ADT, careful consideration should be given to also treating with RT, which is associated with substantial improvements in disease-specific and overall survival and can be delivered with minimal morbidity using modern treatment techniques.”

Can Gleason 7 prostate cancer ever be low-risk? Results from the Shared Equal Access Regional Cancer Hospital (SEARCH) database.

57 Background: Overtreatment of low-risk prostate cancer (PC) is a major issue. Increasing use of active surveillance (AS) will ease this burden. Limited data are available on including men with intermediate risk PC (i.e. Gleason 7) into AS protocols. We examined if a subset of men with Gleason 7 (3+4) PC could be reasonable AS candidates. Methods: We used SEARCH to identify men who had radical prostatectomy from 2001-13 with &gt;8 cores on biopsy and complete data. We compared men who fulfilled low-risk disease criteria (cT1c/T2a; biopsy Gleason ≤6; PSA ≤10 ng/mL) with the exception of biopsy Gleason 7 (3+4) vs. men who met all 3 low-risk criteria. Logistic regression models were used to test the association between biopsy Gleason 3+4 vs. ≤6 and pathological features. Biochemical recurrence (BCR) was examined using multivariable Cox hazards analysis adjusted for clinical and demographic features. To examine if there was a subset of men with low-volume Gleason 7 who would have comparable outcomes to low-risk men, we repeated all analyses limiting the percent positive cores to ≤ 33% and positive cores to ≤ 4, ≤ 3, or ≤ 2. Results: 885 men met inclusion criteria: 505 had low-risk PC and 380 had Gleason 7 low-risk PC. Overall, the Gleason 7 low-risk men had increased risk of pathological Gleason ≥4+3 (p&lt;0.001), positive margins (p=0.069), extracapsular extension (p&lt;0.001), and seminal vesicle invasion (p&lt;0.001) on univariable analysis. Men in the Gleason 7 low-risk group had significantly higher BCR risk (HR 1.65, p=0.004). Analyses were repeated using increasingly strict definitions of low-volume PC. With the exception of higher pathological Gleason score (p&lt;0.001), at ≤3 positive cores, there was no difference in adverse pathological features between groups (all p&gt;0.1). Among men with ≤3 positive cores who met the other low-risk criteria (cT1c/T2a; PSA ≤10 ng/mL), BCR risk was similar in men with Gleason 6 or Gleason 7 (3+4) (HR 1.30; p=0.347) PC. Conclusions: Among men with PSA≤10 ng/mL and stage cT1c/T2a, those with Gleason 7 (3+4) PC in ≤3 positive cores have similar rates of adverse pathology and BCR as men with Gleason ≤6 PC. This finding may expand inclusion criteria of AS protocols to reduce PC overtreatment.

Cost implications and complications of overtreatment of low-risk prostate cancer in the United States.

Evidence-based consensus guidelines recommend only observation for men with low-risk prostate cancer and life expectancy less than 10 years. This report describes the incidence, drivers, cost, and morbidity of overtreatment of low-risk prostate cancer within the United States. The SEER-Medicare Program was used to identify 11,744 men aged 66 years or older diagnosed with low-risk prostate cancer in 2004 through 2007. Overtreatment of prostate cancer was defined as definitive treatment of a patient with a life expectancy of less than 10 years. Expected survival was estimated using NCCN methodology. Costs were the amount paid by Medicare in years after minus year before diagnosis. Toxicities were relevant Medicare diagnoses/interventions. P values are 2-sided. Of 3001 men with low-risk prostate cancer and a life expectancy of less than 10 years, 2011 men (67%) were overtreated. On multivariable logistic regression, overtreated men were more likely to be married (odds ratio [OR], 1.29; 95% CI, 1.05-1.59; P=.02), reside in affluent regions (P<.001), and harbor more advanced disease at diagnosis (P<.001). Two-year toxicity was greater in overtreated patients (P<.001). Relative to active surveillance/watchful waiting/observation, the median additional cost per definitive treatment was $18,827 over 5 years; the cumulative annual cost attributable to overtreatment in the United States was $58.7 million. The ability to avoid treating the 80% of men with low-grade disease who will never die of prostate cancer would save $1.32 billion per year nationally. Overtreatment of low-risk prostate cancer is partially driven by sociodemographic factors and occurs frequently, with marked impact on patient quality of life and health-related costs.

Active surveillance for localized prostate cancer: An analysis of patient contacts and utilization of healthcare resources

Objective. Evidence supports active surveillance (AS) as a means to reduce overtreatment of low-risk prostate cancer (PCa). The consequences of close and long-standing follow-up with regard to outpatient visits, tests and repeated biopsies are widely unknown. This study investigated the trajectory and costs of AS in patients with localized PCa. Materials and methods. In total, 317 PCa patients were followed in a prospective, single-arm AS cohort. The primary outcomes were number of patient contacts, prostate-specific antigen (PSA) tests, biopsies, hospital admissions due to biopsy complications and patients eventually undergoing curative treatment. The secondary outcome was cost. Results. The 5 year cumulative incidence of discontinued AS in a competing-risk model was 40%. During the first 5 years of AS patients underwent a median of two biopsy sets, and patients were seen in an outpatient clinic including PSA testing three to four times annually. In total, 38 of the 406 biopsy sessions led to hospital admission and 87 of the 317 patients required treatment for bladder outlet obstruction (BOO). With a median of 3.7 years’ follow-up, the total cost of AS was euro (€) 1,240,286. Assuming all patients had otherwise undergone primary radical prostatectomy, the cost difference favoured AS with a net benefit of €662,661 (35% reduction). Conclusions. AS entails a close clinical follow-up with a considerable risk of rebiopsy complication, treatment of BOO and subsequent delayed definitive therapy. This risk should be weighed against a potential economic benefit and reduction in the risk of overtreatment compared to immediate radical treatment.

Risk-Based Prostate Cancer Screening: Who and How?

The purpose of this review is to identify clinical risk factors for prostate cancer and to assess the utility and limitations of our current tools for prostate cancer screening. Prostate-specific antigen is the single most important factor for identifying men at increased risk of prostate cancer but is best assessed in the context of other clinical factors; increasing age, race, and family history are well-established risk factors for the diagnosis of prostate cancer. In addition to clinical risk calculators, novel tools such as multiparametric imaging, serum or urinary biomarkers, and genetic profiling show promise in improving prostate cancer diagnosis and characterization. Optimal use of existing and future tools will help alleviate the problems of overdiagnosis and overtreatment of low-risk prostate cancer without reversing the substantial mortality declines that have been achieved in the screening era.

Overtreatment of low-risk prostate cancer in the United States: Incidence, cost, complications, and implications for the screening debate.

161 Background: The National Comprehensive Cancer Network (NCCN) recommends active surveillance as the sole option for men with low-risk prostate cancer (LRPC) and a life expectancy &lt;10 years. We sought to describe the incidence, risk factors, cost, and morbidity related to overtreatment of LRPC within the United States. Methods: We used the Surveillance, Epidemiology and End Results (SEER)-Medicare Program to identify 11,744 men ≥66 years with LRPC diagnosed from 2004-2007. Expected survival was estimated using the 2007 Social Security Life Table and was increased and decreased by 50% in men in the upper and lower quartiles of comorbidity, respectively, as specified by the NCCN. Overtreatment was definitive treatment in men with LRPC and life expectancy &lt;10 years. Costs were the amount paid by Medicare in the year following minus the year prior to diagnosis. Toxicities were defined as relevant Medicare diagnoses or interventions. Results: Of 3001 men with LRPC and a life expectancy &lt;10 years, 2011 (67%) were treated definitively. On multivariable logistic regression, men overtreated for prostate cancer were more likely to be younger (p&lt;.001), white (vs black, OR 1.44, 95% CI 1.03-2.02, p=.03), married (OR 1.30, 95% CI 1.05-1.61, p=.02), urban (trend, OR 1.40, 95% CI 0.98-2.00, p=.06), have higher Elixhauser comorbidity (p&lt;.001), and have a higher clinical stage (T2 vs T1, OR 1.57, 95% CI 1.19-2.07, p=.001) and prostate-specific antigen level (OR 1.02, 95% CI 1.02-1.02, p&lt;.001). Relative to expectant management, the mean added cost per definitive treatment was $15,308. When extrapolated nationally the cumulative net cost of overtreatment in men ≥66 years is $32 million per annum. Long-term urinary, erectile, and bowel toxicity occurred in 59.2% and 50.0%, 47.9% and 19.7%, and 7.1% and 17.8% of prostatectomy and radiation patients, respectively. Conclusions: Overtreatment of prostate cancer is partially driven by sociodemographic factors and occurs in a high percentage of men with LRPC and limited life expectancy, with marked impact on patient quality of life and health care costs. Efforts to enhance appropriate management of LRPC would reduce the harms associated with screening.

Certificate of Need (CON) Status and its Impact on Overtreatment of Low-risk Prostate Cancer in the Elderly

Certificate of Need (CON) Status and its Impact on Overtreatment of Low-risk Prostate Cancer in the Elderly

Active surveillance for low-risk prostate cancer.

Active surveillance for localized prostate cancer entails initial expectant management rather than immediate therapy, with “curative-intent” treatment deferred until there is evidence that the patient is at increased risk for disease progression. This is a response to the clearly documented risks of over diagnosis and overtreatment of low-risk prostate cancer, which in most cases poses little or no threat to the patient. It is based upon the prolonged natural history of prostate cancer and is an attempt to balance the risks and side effects of overtreatment against the possibility of disease progression and a lost opportunity for cure. Low-risk prostate cancer is more accurately viewed as one of multiple risk factors for the presence of higher grade prostate cancer. Like atypical small acinar proliferation, (ASAP), it may be managed with close follow up but without radical intervention, unless there is clear evidence of more aggressive disease.

Decreased Physician Reimbursement for Hormone Therapy May Have Reduced Over-treatment of Low-risk Prostate Cancer

Decreased Physician Reimbursement for Hormone Therapy May Have Reduced Over-treatment of Low-risk Prostate Cancer