Characteristics and outcomes of participants in colorectal cancer biomarker trials versus a real-world cohort

The restrictive eligibility criteria of therapy-focused cancer clinical trials can limit the external validity of the results. The characteristics and survival outcomes of patients enrolled in stand-alone biomarker studies have yet to be explored. We examined the characteristics of patients enrolled in a series of biomarker studies in stage II and III colorectal cancer (CRC) and of the broader patient population from which the study cohorts were recruited. We examined three distinct trial scenarios: a retrospective cohort study (RCS) where archival tissue samples were analyzed, a prospective observational study (POS) where blood samples were collected but patients received standard treatment and a randomized clinical trial (RCT) where biomarker analysis could inform clinical care. Clinical data for each study time period were extracted from a prospective registry. For all CRC patients (n = 4033) in this study, the median age was 70 years and 54% were ECOG 0. For patients in the RCS (n = 450), POS (n = 284) and RCT (n = 230), the median age was 72, 65 and 64 years, with 45%, 74% and 79% being ECOG 0. For the POS and RCT, 33% and 36% of all patients with the relevant disease stage were enrolled over the study recruitment period. Survival outcomes were similar for patients in the RCS and POS. RCT outcome data are not available. As for therapy-based trials, enrollment in prospective biomarker studies may be selective, despite relatively broad eligibility criteria. Characteristics and recruitment were similar for POS and RCT patients, indicating study complexity may not necessarily limit patient recruitment. For the prospective biomarker study cohorts examined, the selective recruitment did not significantly impact survival outcomes, suggesting potential for high external validity.

以治疗为导向的癌症临床试验所采用的限制性入组标准，可能会限制其研究结果的外部有效性。独立生物标志物研究的入组患者特征与生存结局，目前仍有待探索。本研究针对Ⅱ期与Ⅲ期结直肠癌（colorectal cancer, CRC）患者，分析了系列生物标志物研究的入组患者特征，以及招募该等研究队列的总体患者人群特征。本研究考察了三种不同的试验场景：一是回顾性队列研究（retrospective cohort study, RCS），该研究对存档组织样本进行分析；二是前瞻性观察性研究（prospective observational study, POS），研究采集患者血液样本但患者仅接受标准治疗；三是随机临床试验（randomized clinical trial, RCT），生物标志物分析可用于指导临床诊疗。各研究周期的临床数据均提取自前瞻性登记数据库。本研究纳入的全部结直肠癌患者共4033例，中位年龄为70岁，其中54%的患者ECOG体能状态评分为0分。在回顾性队列研究（n=450）、前瞻性观察性研究（n=284）与随机临床试验（n=230）的入组患者中，中位年龄分别为72岁、65岁与64岁，ECOG评分为0分的患者占比分别为45%、74%与79%。在研究招募周期内，符合对应疾病分期的全部患者中，分别有33%与36%的患者入组前瞻性观察性研究与随机临床试验。回顾性队列研究与前瞻性观察性研究患者的生存结局相似，目前暂无随机临床试验的结局数据。与以治疗为核心的临床试验一致，尽管前瞻性生物标志物研究的入组标准相对宽泛，但其患者入组仍可能存在选择性偏倚。前瞻性观察性研究与随机临床试验的患者特征及招募情况均相似，这提示研究复杂度未必会制约患者招募。针对本研究考察的前瞻性生物标志物研究队列，选择性入组并未对生存结局造成显著影响，提示此类研究或具备较高的外部有效性。