Seyed Qaderi

Colorectal cancer (CRC) is the third most common cancer worldwide. In the Netherlands, more than 14,000 new patients are diagnosed with CRC annually and the majority of them undergo (surgical) treatment. After curative CRC treatment, patients are followed to detect and treat early disease recurrence or metastases. Also, follow-up is designed to consult patients regarding complications, adverse effects and long-term consequences, and to provide outcome data. The continuous improvement of CRC care and survival resulted in more CRC survivors requiring follow-up care. This puts more pressure on the follow-up system and comes with a rise of total health care costs. Besides, current guidelines are rather “one size fits all” than “which size fits who”, lacking patient-centeredness. The provider, setting and manner of follow-up is subject to debate. Changes and improvements are required to provide and maintain high-quality follow-up care. The aim of this thesis was to study various aspects of follow-up care from different perspectives and hereby provide a comprehensive overview on how follow-up after treatment for stage I-III CRC can be reorganized.

Part I includes three chapters about survival and recurrence outcomes following treatment for stage I-III CRC. The increasing number of CRC survivors require adequate and up-to-date information on their survival prospects and life expectancy. Communicating such information can be challenging, because patients often find it difficult to understand probabilities. Moreover, traditional survival estimates provide an overly pessimistic prognosis for patients who have survived an initial period after diagnosis. Therefore, alternative measures for reporting patient survival such as conditional survival, cure modelling and loss in expectation of life were examined in Chapter 2 and 3. In Chapter 2, a large-scale population-based study using data of the Netherlands Cancer Registry (NCR) was presented. Conditional survival, time-to-cure and cure fractions were determined for more than 175,000 patients diagnosed with stage I-III CRC between 1995-2016 and followed up to 2019. Current survival estimates of patients with cancer are commonly determined using relative survival or overall methods, with survival reported as a function of time since diagnosis. Due to postoperative, in hospital and up to 90-day mortality, excess mortality resulting from CRC is highest in the first year after diagnosis, especially in the geriatric population. Thus, published estimates of survival provide an overly pessimistic prognosis for patients who have survived an initial period after treatment. Conditional survival on the other hand, provides up-to-date and specific survival outcome information relevant for (long-term) CRC survivors. In our study, conditional survival improved substantially, and the increments were highest in more advanced disease stages. Having survived 5-years, the conditional survival of those with stage III colon and rectal was 92% and 85%. Moreover, cure proportions increased as well, illustrating improved survival and cure after CRC surgery.

In Chapter 3, another population-based study quantified the impact of CRC diagnosis on patient’s life expectancy. Using data from the NCR, estimates of loss in expectation of life (LEL) among over 200,000 patients diagnosed with stage I-III CRC between 1990-2016 were presented and discussed. Compared to traditional 5-year relative or overall survival, LEL is a more intuitive measure that can be easily interpreted and communicated to patients. Moreover, LEL can be a meaningful lifetime measure to understand how much cancer affects the patient’s future lifespan. In our study, LEL decreased and the decline was highest in more advanced disease stages. In 2010, LEL for 60-year old male and female patients was 7 vs. 8 years for colon cancer, and 7 vs. 8 years for rectal cancer, respectively. These findings reflect the increased survival and therefore, decreasing impact of cancer on life expectancy. In an era of multidisciplinary treatment strategies and emphasis on shared-decision making, the results of the above mentioned two studies provide up-to-date, meaningful and clinically relevant survival outcome information that can be used during outpatient appointments. Also, physicians and policy-makers are reassured of the positive effect of their efforts and attempts to improve CRC care.

Another important aspect for patients in follow-up is disease recurrence. At the end of the day, patients would like to know about the risk of disease recurrence. In a recent and large population-based study using recurrence information of over 5,400 patients diagnosed with stage I-III CRC between January and July 2015 (Chapter 4), the cumulative incidence (CI) of recurrence was studied and the pattern and distribution of metachronous metastases were determined. Patients were followed up to December 2020. The 3-year CI of recurrences were lower than described in the literature and anatomical sublocations of CRC seemed to influence the metastatic pattern and risk of recurrence considerably. This information can be used to risk-stratify and identify patients requiring personalized and/or close surveillance.

Part II includes three chapters regarding the organization of follow-up care in the Netherlands, care utilization, adherence to national guidelines, and symptom burden during follow-up. Since the number of follow-up patients increased over the years due to improved outcome and increased incidence, more patients are challenged and impaired by the psychosocial and physical side-effects of cancer diagnosis and subsequent treatment. In Chapter 5, the results of a cross-sectional survey held among 106 CRC surgeons in the Netherlands in 2019 regarding the frequency, content and provider of follow-up were presented. Also, adherence to guidelines and differences in clinical practice were examined. The findings of this survey demonstrated that adherence to minimal guideline recommendations (biannual clinical visits, CEA sampling and abdominal ultrasound (US) during the first follow-up year) was high (99%), but that there was variation in content and frequency of follow-up modalities. Around 61% and 78% of the surgeons performed a more intensive regimen, consisting of four-yearly clinical visits and CEA tests, and a smaller percentage of 11% of the participants performed a Computed Tomography (CT)-scan instead of abdominal US. In Chapter 6, cancer-related follow-up in both primary care and hospital, and adherence to national guidelines were evaluated in a cohort of 2,450 with stage I-III CRC that had undergone endoscopic or surgical treatment with curative intent between 2000-2009 and completed questionnaires in 2010. Moreover, risk factors for increased follow-up care use were discussed. According this cohort study, most CRC survivors received follow-up care and the majority was comfortable with their current follow-up schedule. Although patients were predominantly followed according to guidelines, substantial variation in follow-up practice existed, with both under and overuse of care. Advanced disease stage, receipt of chemotherapy, low socioeconomic status, the presence of a stoma, and fatigue were factors associated with overuse of follow-up care. Another, smaller group, received less follow-up visits than recommended. Future studies should investigate how overconsumption can be reduced, while still addressing patients’ needs.

In Chapter 7, the results of a large-scale population-based study among 1,535 patients diagnosed with stage I-III CRC between 2013-2018 regarding quality of life (QoL), psychological distress, and symptom burden after CRC treatment were presented. The vast majority of CRC patients did well and reported high scores on functional QoL scales and their scores were comparable to the normative population by 12-months follow-up. These patients appear to be suitable for a more flexible and dynamic follow-up mode that differs from the traditional hospital-based follow-up. However, our study also revealed a vulnerable patient group of approximately 13% who reported either low, not improving QoL or high levels of psychological distress throughout 24-months follow-up. Female patients, patients with younger age, lower educational level, disease stage II-III and major LARS were at risk for belonging to this patient group. Early pre and postoperative screening on these factors may identify these vulnerable patients and they should be counselled for personalized (tailored) follow-up.

Part III includes two chapters regarding experiences with the development and implementation of and initial results of remote follow-up. To provide more patient-centered follow-up, decrease costs, and overcome restrictions due to (future) global pandemics such as the current COVID-19 pandemic, it is likely that hospital follow-up will become less dominant in the future. In Chapter 8, the experiences with the development and implementation of a novel remote follow-up plan for patients treated for stage I-III CRC at the Radboud university medical center in Nijmegen, the Netherlands were discussed. Among these patient group, a prospective questionnaire study was performed regarding patient satisfaction, QoL, care utilization and costs. The findings of this study were presented in Chapter 9. A total of 118 patients have been followed according to the new remote follow-up regimen. Overall satisfaction towards remote follow-up at 6-and 12-months was rated 7.8 and 7.5 out of 10. Satisfaction with the online self-management information was rated 8 out of 10. Over a one-year period, QoL remained high and patients experienced low FCR. More than 70% of the patients self-organized their care, while the others sought contact via telephone, MyChart or hospital visits. Remote follow-up for the total cohort led to €22,408 cost-savings over one-year compared to standard hospital follow-up. The present study shows that the implementation of a remote follow-up plan comes with high cost savings, while not sacrificing QoL or increasing fear of cancer recurrence (FCR). Therefore, a transition from standard hospital follow-up towards remote follow-up care could help to minimize costs without compromising the quality of health care. This study supports the further implementation of remote follow-up in colorectal oncology practices.

In Chapter 10, a state-of-the-art review of the literature evaluating setting, manner and provider of CRC follow-up and patient and health care attitudes towards standard and alternative follow-up regimens, is outlined. The findings of this review were used and adapted in the general discussion. Overall, this comprehensive thesis examined important aspects of follow-up. To decrease the personal and financial burden of follow-up care for a growing number of CRC survivors, it is likely that hospital follow-up will become less common. Remote follow-up was found cost-effective and acceptable. This thesis supports further personalization of follow-up. Future large-scale multicenter studies should investigate whether remote follow-up schedules can be implemented on a national level.