Use of Conservative Management for Low-Risk Prostate Cancer in the Veterans Affairs Integrated Health Care System From 2005-2015

BACKGROUND: Certain patients with intermediate-risk prostate cancer (PCa) may be appropriate candidates for active surveillance (AS). In the current study, the authors sought to characterize AS use and early mortality outcomes for patients with intermediate-risk PCa in the United States. METHODS: The novel Surveillance, Epidemiology, and End Results Active Surveillance/Watchful Waiting database identified 52,940 men diagnosed with National Comprehensive Cancer Network intermediate-risk PCa (cT2b-c, Gleason score of 7, or a prostate-specific antigen level of 10-20 ng/mL) and actively managed (AS, radiotherapy, or radical prostatectomy) from 2010 through 2015. The Cuzick test assessed AS time trends, and logistic multivariable regression characterized features associated with AS. Fine-Gray and Cox modeling determined PCa-specific mortality (PCSM) and overall survival, respectively. RESULTS: The rate of AS increased from 3.7% in 2010 to 7.3% in 2015, and from 7.2% to 11.7% among men aged ≥70 years. Among men with favorable and unfavorable intermediate-risk disease, the use of AS increased from 7.2% to 14.9% and from 2.2% to 3.8%, respectively (all P value for trend, <.001). The mean age of those patients managed with AS decreased from 69.9 years to 67.9 years (P = .0004). Factors found to be associated with AS included favorable risk disease; black race; higher socioeconomic status; older age; and diagnosis in the West, Northwest, or Midwest regions of the United States. The 5-year PCSM rate was comparable to AS versus treatment among patients with low-risk and favorable intermediate-risk disease, but was worse with AS among those with unfavorable intermediate-risk disease (PCSM, 1.3% vs 0.5%; adjusted hazard ratio, 2.48 [95% CI, 1.11-5.50; P = .026]) and intermediate-risk disease overall (PCSM, 1.1% vs 0.4%; adjusted hazard ratio, 2.34 [95% CI, 1.25-4.37; P = .008]). CONCLUSIONS: The use of AS for patients with intermediate-risk PCa is increasing across the United States, particularly for older men and those with favorable intermediate-risk disease. Early estimates of cancer-specific and overall mortality rates are low with AS, although significantly higher compared with treatment. Cancer 2019;125:3164-3171.

Section: Discussionmentioning

confidence: 63%

Use and early mortality outcomes of active surveillance in patients with intermediate‐risk prostate cancer

Butler

Mahal

Lamba

et al. 2019

“…24 Conversely, our evidence also supports potential clinician and patient ambivalence toward missed opportunity for cure. 30 To address these limitations, the current study represents the largest inclusion of young patients with a quality-assured AS/WW variable. Furthermore, lower absolute rates of AS/WW utilization in younger patients suggests that there is more ambivalence and uncertainty toward managing younger patients than older patients with conservative management.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, other large US national database studies have used a proxy for AS/WW to compare conservative management with other treatment, rather than using a validated variable for AS/WW. 30 To address these limitations, the current study represents the largest inclusion of young patients with a quality-assured AS/WW variable. Therefore, our findings could serve as a national standard for comparing utilization and outcomes associated with AS/WW in LRPC across age groups.…”

Section: Discussionmentioning

confidence: 99%

Conservative management of low‐risk prostate cancer among young versus older men in the United States: Trends and outcomes from a novel national database

Mahal

Butler

Franco

et al. 2019

BACKGROUND: Management for men aged ≤55 years with low-risk prostate cancer (LRPC) is debated given quality-of-life implications with definitive treatment versus the potential missed opportunity for cure with conservative management. The objective of this study was to define rates of conservative management for LRPC and associated short-term outcomes in young versus older men in the United States. METHODS: The nonpublic Surveillance, Epidemiology, and End Results Prostate with Active Surveillance/ Watchful Waiting (AS/WW) Database identified 50,302 men who were diagnosed with LRPC from 2010 through 2015. AS/WW rates in the United States were stratified by age (≤55 vs ≥56 years). Prostate cancer-specific mortality and overall mortality were defined by initial management type (AS/WW vs definitive treatment [referent]) and age. RESULTS: AS/WW utilization increased from 8.61% (2010) to 34.56% (2015) among men aged ≤55 years (P for trend <0.001) and from 15.99% to 43.81% among men aged ≥56 years (P for trend <.001). Among patients who had ≤2 positive biopsy cores, AS/WW rates increased from 12.90% to 48.78% for men aged ≤55 years and from 21.85% to 58.01% for men aged ≥56 years. Among patients who had ≥3 positive biopsy cores, AS/WW rates increased from 3.89% to 22.45% for men aged ≤55 years and from 10.05% to 28.49% for men aged ≥56 years (all P for trend <.001).Five-year prostate cancer-specific mortality rates were <0.30% across age and initial management type subgroups. CONCLUSIONS: AS/WW rates quadrupled for patients aged ≤55 years from 2010 to 2015, with favorable short-term outcomes. These findings demonstrate the short-term safety and increasing acceptance of AS/WW for both younger and older patients. However, there are still higher absolute rates of AS/WW in older patients (P < .001), suggesting some national ambivalence toward AS/WW in younger patients. Cancer 2019;125:3338-3346.

“…These ideas are upheld by Loeb and colleagues' Markov model for men with localized prostate cancer who elected for either AS or WW. 9 Despite the incorporation of AS as a management strategy for patients with low-risk prostate cancer, the use of AS protocols remains an area of controversy in younger men. Definitive management options were still available to patients on AS protocols, because 30% to 41% underwent treatment within 10 years of initial diagnosis.…”

mentioning

confidence: 99%

“…This increase was primarily because of the increase in the use of AS, from 4% use in 2005 to 39% in 2015. 9 Despite the incorporation of AS as a management strategy for patients with low-risk prostate cancer, the use of AS protocols remains an area of controversy in younger men. This stems from concerns with the burden of continued follow-up, potential missed opportunities for cure, and the psychological burden of patients knowing they harbor a malignancy.…”

mentioning

confidence: 99%

Increasing the use of active surveillance for prostate cancer in younger men

Fang

Glaser

Rais‐Bahrami

2019

Prostate cancer is the second most common malignancy and the fifth leading cause of cancer-related deaths in men worldwide. 1 This dichotomy in incidence and mortality is largely because of the disease's long latency period and slow growth rate, which permit early detection. Although the prevalence of prostate cancer increases with age, autopsy studies have demonstrated a relatively high rate of occult prostate cancer: from 2.8% to 35.4% in men aged 40 to 49 years and from 7.9% to 45.9% in men aged 50 to 59 years, varying by race. 2 However, the slow rate of disease progression results in many men dying of other causes. This is especially important when considering potentially compromised sexual, urinary, and bowel quality-of-life measures among men who have undergone intervention for prostate cancer. Therefore, balancing the timing of intervention in young men with low-risk, localized prostate cancer to postpone or avoid these potential side effects without comprising oncologic outcomes is an important area of active investigation.In this issue of Cancer, Mahal et al examine the national rates of conservative management for low-risk prostate cancer and their short-term outcomes in the largest cohort of men aged ≤55 years. Using the Surveillance, Epidemiology, and End Results (SEER) database, 50,302 men were evaluated between 2010 and 2015. The use of conservative management increased in men aged ≤55 years (from 8.61% to 34.56%; P < .001) and in men aged >55 years (from 15.99% to 43.81%; P < .001). Furthermore, ≤2 positive cores, higher socioeconomic status, age ≥56 years, and diagnosis after 2012 were all factors associated with conservative therapy (P < .001). Five-year prostate cancer-specific mortality rates were <0.3% across all ages irrespective of whether conservative management strategies were used. 3 Although there remains no consensus on the management of low-risk prostate cancer in young men, there is an obvious increase in the use of these conservative management strategies, which take into account these men's safety and quality of life.Conservative management is accomplished by 1 of 2 strategies: watchful waiting (WW) or active surveillance (AS). WW is generally offered to patients with shorter life expectancy and significant comorbidities. Definitive treatment options are forgone in lieu of monitoring a patient's disease progression, typically to a higher stage with metastatic spread, and palliatively managing symptoms to preserve their quality of life. Conversely, AS involves the intensive monitoring of disease progression to higher grade groups or risk strata with expectations to intervene if such progression is detected, with the goal of staving off treatment and its side effects if the disease remains indolent. These ideas are upheld by Loeb and colleagues' Markov model for men with localized prostate cancer who elected for either AS or WW. Those authors demonstrated more life-years and quality-of-life years with AS than with WW, except in patients aged >65 years or when treatment-related compli...