Ryser Marc D, Worni Mathias, Turner Elizabeth L, Marks Jeffrey R, Durrett Rick, Hwang E Shelley
Department of Mathematics (MDR, RD) and Duke Global Health Institute (ELT), Duke University, Durham, NC; Division of Advanced Oncologic and GI Surgery (MDR, MW, ESH) and Division of Surgical Sciences (JRM), Department of Surgery, Duke University Medical Center, Durham, NC; Department of Visceral Surgery and Medicine, Inselspital, Berne University Hospital and University of Berne, Berne, Switzerland (MW); Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, NC (ELT).
J Natl Cancer Inst. 2015 Dec 17;108(5). doi: 10.1093/jnci/djv372. Print 2016 May.
Ductal carcinoma in situ (DCIS) is a noninvasive breast lesion with uncertain risk for invasive progression. Usual care (UC) for DCIS consists of treatment upon diagnosis, thus potentially overtreating patients with low propensity for progression. One strategy to reduce overtreatment is active surveillance (AS), whereby DCIS is treated only upon detection of invasive disease. Our goal was to perform a quantitative evaluation of outcomes following an AS strategy for DCIS.
Age-stratified, 10-year disease-specific cumulative mortality (DSCM) for AS was calculated using a computational risk projection model based upon published estimates for natural history parameters, and Surveillance, Epidemiology, and End Results data for outcomes. AS projections were compared with the DSCM for patients who received UC. To quantify the propagation of parameter uncertainty, a 95% projection range (PR) was computed, and sensitivity analyses were performed.
Under the assumption that AS cannot outperform UC, the projected median differences in 10-year DSCM between AS and UC when diagnosed at ages 40, 55, and 70 years were 2.6% (PR = 1.4%-5.1%), 1.5% (PR = 0.5%-3.5%), and 0.6% (PR = 0.0%-2.4), respectively. Corresponding median numbers of patients needed to treat to avert one breast cancer death were 38.3 (PR = 19.7-69.9), 67.3 (PR = 28.7-211.4), and 157.2 (PR = 41.1-3872.8), respectively. Sensitivity analyses showed that the parameter with greatest impact on DSCM was the probability of understaging invasive cancer at diagnosis.
AS could be a viable management strategy for carefully selected DCIS patients, particularly among older age groups and those with substantial competing mortality risks. The effectiveness of AS could be markedly improved by reducing the rate of understaging.
导管原位癌（DCIS）是一种非侵袭性乳腺病变，其侵袭性进展风险不确定。DCIS的常规治疗（UC）包括诊断后即进行治疗，因此可能会过度治疗进展倾向较低的患者。减少过度治疗的一种策略是主动监测（AS），即仅在检测到侵袭性疾病时才对DCIS进行治疗。我们的目标是对DCIS的AS策略后的结局进行定量评估。
使用基于已发表的自然史参数估计值的计算风险预测模型以及监测、流行病学和最终结果数据来计算AS的年龄分层10年疾病特异性累积死亡率（DSCM）。将AS预测结果与接受UC治疗的患者的DSCM进行比较。为了量化参数不确定性的传播，计算了95%预测范围（PR），并进行了敏感性分析。
在AS不能优于UC的假设下，40岁、55岁和70岁诊断时AS与UC之间预测的10年DSCM中位数差异分别为2.6%（PR = 1.4%-5.1%）、1.5%（PR = 0.5%-3.5%）和0.6%（PR = 0.0%-2.4%）。为避免一例乳腺癌死亡所需治疗的相应患者中位数分别为38.3（PR = 19.7-69.9）、67.3（PR = 28.7-211.4）和157.2（PR = 41.1-3872.8）。敏感性分析表明，对DSCM影响最大的参数是诊断时侵袭性癌分期过低的概率。
对于精心挑选的DCIS患者，尤其是老年组和具有大量竞争性死亡风险的患者，AS可能是一种可行的管理策略。通过降低分期过低的发生率，AS的有效性可得到显著提高。
