Physiological and psychosocial aspects of reproductive health after early-onset colorectal cancer

摘要 尽管在育龄期间被诊断为结直肠癌(CRC)、接受治疗并存活下来的成年人数量很多，但在18至49岁的早发性结直肠癌(CRC)成年人及其家人中，生殖健康问题仍然是一个未得到满足的护理需求。这是因为缺乏前瞻性数据来客观地衡量结直肠癌及其治疗方法在这一患者群体中随着时间的推移对生育力和性健康的有害影响。鉴于过去几十年来早发性结直肠癌发病率不断上升的原因，现在是我们解决这些未得到满足的生育和性保健需求的时候了，以便改善这一不断增长的育龄结直肠癌幸存者的结果。因此，这项研究是专门为解决长期未得到满足的需求并实现其首要目标而设计的：在诊断出早发性结直肠癌后，确定结直肠癌治疗引起的性腺功能的变化，并调查性健康和生育的心理社会层面。我们将使用验证的胎膜早破是性功能和满意度(SexFS)，PROIS-29核心健康，与生活方式和生殖健康相关的问卷，以及定性访谈(目标1)，以前瞻性地定义诊断、治疗和监测时间点的生殖健康的心理维度；以及这些测量随时间的变化。这将告知最高生殖健康问题和需求，特别是早发性结直肠癌患者在整个癌症护理连续过程中的统一时间点。然后，我们将使用同时收集的空腹血样(AIM 2)和详细的临床和治疗数据，前瞻性地量化三个统一研究时间点的结直肠癌治疗对性腺功能的影响。这两个具体目标利用了相同的研究人群--结直肠癌后保留生育能力(序言)研究队列，该研究队列在范德比尔特-英格拉姆癌症中心招募了总共220名年龄在18岁至49岁之间的新诊断的CRC患者。AIM 2的所有实验室检测将在获得CUA认证和CDC认证的实验室中，使用FDA批准的AMH、雌二醇、FSH、SHBG、LH、DHEAS、抑制素B、睾酮、DHT和雄烯二酮的临床免疫检测方法进行。总体而言，这项研究在概念上是创新的，因为我们的队列配对标准化、空腹采血，具有健壮的性健康、生育力、生殖史、月经模式、社会人口学、暴露和生活质量数据，并且比先前在早发性结直肠癌中与生育相关的研究多11倍。该项目将从一个独特的队列中产生重要的新数据，并从统计上推动在协调一致的生殖保健评估和针对育龄CRC患者的身体/心理社会支持战略方面取得重大进展。我们的发现将导致将生殖保健纳入早发性结直肠癌的临床治疗，并最终改善针对这一患者群体的临床结果。

SUMMARY Despite the number of adults within their child-bearing years diagnosed with, treated for, and surviving colorectal cancer (CRC), reproductive health concerns stand as an unmet care need among adults ages 18 to 49 years with CRC (early-onset CRC) and their families. This is because there is a paucity of prospective data to objectively measure the deleterious effects of CRC and its therapies on fertility and sexual health over time within this patient population. Given the unexplained, rising incidence of early-onset CRC over the last decades, the time is now for us to address these unmet fertility and sexual health care needs in order to improve outcomes within this growing population of reproductive age CRC survivors. Thus, this study is specifically designed to address a long-standing unmet need and achieve its overarching goal: to identify changes in gonadal function caused by CRC treatments and investigate psychosocial dimensions of sexual health and fertility-after a diagnosis of early-onset CRC. We will use validated PROM IS sexual function and satisfaction (SexFS), PROMIS-29 core health, lifestyle-related and reproductive health questionnaires, and qualitative interviews (Aim 1) to prospectively define the psychological dimensions of reproductive health at diagnosis, treatment and surveillance timepoints; as well as changes in these measures over time. This will inform the highest reproductive health concerns and needs specifically for early-onset CRC patients at uniform timepoints across the cancer care continuum. We will then use fasting blood samples (Aim 2) and detailed clinical and treatment data that are collected in parallel to prospectively quantify the impact of CRC therapies on gonadal function at three uniform study timepoints. Both specific aims utilize the same study population--the PREserving Fertility After Colorectal CancEr (PREFACE) Study cohort that is enrolling a total of 220 newly-diagnosed CRC patients between ages 18 and 49 years at Vanderbilt-Ingram Cancer Center. All laboratory assays in Aim 2 will be conducted using FDA-approved clinical immunoassays for AMH, estradiol, FSH, SHBG, LH, DHEAS, inhibin B, testosterone, DHT, and androstenedione in a CUA-accredited and CDC-certified laboratory. Overall, this study is conceptually innovative in that our cohort pairs standardized, fasting blood collection with robust sexual health, fertility, reproductive history, menstrual patterns, sociodemographic, exposures, and quality of life data, and is 11-fold larger than previous fertility-related studies in early-onset CRC. This project will generate crucial new data from a unique cohort and is statistically powered to drive significant advances toward concordant reproductive health care assessment and physical/psychosocial support strategies specific to CRC patients of reproductive age. Our findings will lead to incorporating reproductive health care in the clinical management of early-onset CRC, and ultimately improve clinical outcomes specifically for this patient population.