Elsevier

European Journal of Cancer

Volume 51, Issue 13, September 2015, Pages 1675-1682
European Journal of Cancer

Comparable survival for young rectal cancer patients, despite unfavourable morphology and more advanced-stage disease

https://doi.org/10.1016/j.ejca.2015.06.005Get rights and content

Abstract

Background

Young patients with rectal cancer tend to present with more advanced-stage disease and unfavourable tumour morphology. The effects of these tumour characteristics on survival in this particular patient group are unclear.

Methods

Population-based data from the Netherlands Cancer Registry (NCR) were used. Data from patients diagnosed with rectal cancer between 1989 and 2010 were selected. Younger patients (⩽40 years) were compared with middle-aged patients (41–70 years) with respect to disease stage, tumour characteristics, treatment and outcomes. Patients aged older than 70 years were excluded. Relative excess risk (RER) models were used to perform uni- and multivariate survival analyses.

Findings

A total of 37.056 patients were included (⩽40 years n = 1.102). Compared with middle-aged patients, young patients were more likely to have stage III (33.8% versus 27.8%) and stage IV (24.3% versus 19.6%) disease (p < 0.001). Young patients also presented more frequently with mucinous tumours (10.8% versus 9.0%), signet cell carcinomas (2.6% versus 0.6%) and poorly differentiated tumours (16.6% versus 12.3%) (p = 0.001). The treatment of stage I–III patients did not differ between the two groups, except regarding adjuvant chemotherapy, which was more often given to young patients (24.3% versus 14.4%, p < 0.001). Young age was a prognostic factor for better survival in stage I–III patients (RER 0.82 CI 0.71–0.94). Adjuvant chemotherapy was associated with improved survival in stage I–III patients (RER 0.76, 95%CI 0.70–0.83). In an exploratory analysis, adjuvant chemotherapy in young stage III and pN1 patients was associated with improved survival.

Concluding statement

Young patients present with more advanced disease and have more unfavourable tumour characteristics compared with middle-aged patients. Despite these characteristics, survival rates are equal, and young age is a prognostic factor for better survival. Although the use of adjuvant chemotherapy is controversial, a positive correlation with survival was found in this study.

Introduction

Colorectal cancer is the second most common malignancy worldwide [1]. In the Netherlands, it is the third most frequent type of cancer. Approximately one-third of patients with a colorectal malignancy have rectal carcinoma. In 2013, almost 4000 new cases of rectal cancer were diagnosed in the Netherlands [2]. Rectal cancer mainly affects middle-aged and elderly individuals, with more than 75% of patients being diagnosed at 60 years or older [2], [3]. However, during the last several decades, an increasing incidence of patients diagnosed with rectal cancer at the age of 40 years or younger has been observed [4], [5].

Young patients with rectal cancer more often present with advanced-stage disease and unfavourable tumour morphology compared with middle-aged patients [6], [7], [8], [9], [10]. Studies focusing on survival in young rectal cancer patients have shown at least equal or better outcomes compared with older patients [9], [10]. However, other studies have found contradictory survival rates when young patients present with more advanced disease [6], [11].

Overall, the assumption that young patients with rectal cancer have poorer survival is mainly based on studies performed prior to or during the introduction of total mesorectal excision (TME) surgery and neo-adjuvant treatment schemes with radiation and/or chemotherapy [11], [12]. More recent studies have been smaller and included patients with both colon and rectal cancer, leading to uncertainty about the possible effects of adverse tumour morphology and advanced-stage disease on survival in young rectal cancer patients [6], [8], [10], [13], [14].

For stage III colon cancer patients, there is a significant survival benefit from adjuvant chemotherapy, regardless of age [15], [16]. However, for stage III rectal cancer, there is a lack of consensus regarding adjuvant treatment amongst multidisciplinary experts and in international guidelines [17], [18]. Additionally, no distinctions are made regarding age, likely due to lack of information about the effect of adjuvant chemotherapy in young rectal cancer patients. In randomised controlled trials only a minority of the patients can be considered young (⩽40 years). In the most recent meta-analysis about adjuvant chemotherapy after pre-operative (chemo-)radiochemotherapy in rectal cancer less than 2% of the 1196 included patients were under the age of 45 years [19]. To obtain further insights concerning the influence of adjuvant chemotherapy on survival in young patients, large population-based studies may be performed, but tumour and treatment characteristics are not always available in these databases.

In both younger and middle-aged patients, life expectancy is good and is less confounded by other variables, such as co-morbidities or age-dependent physiological decline, unlike in elderly patients. Therefore, this study was conducted to investigate the differences in tumour stage, morphology, treatment and survival between young (aged  40 years) and middle-aged (41–70 years) rectal cancer patients in a large, nationwide population-based database of patients diagnosed with rectal cancer in the Netherlands. In a secondary analysis, the influence of adjuvant chemotherapy on survival was investigated only in young patients because these patients are the least likely to be affected by confounding variables.

Section snippets

Patients and methods

For this study, population-based data from the Netherlands Cancer Registry (NCR) were used. The NCR has collected data on all newly diagnosed patients with cancer in the Netherlands since 1989. Registration is primarily based on notification by the automated pathology archive (PALGA) and hospital discharge notes. Clinical and demographic information, tumour characteristics and primary treatment are routinely extracted from medical records by specially trained administrators of the cancer

Patient and tumour characteristics

A total of 66,581 patients with primary rectal cancer were registered by the NCR between 1989 and 2010. Patients older than 70 years were excluded, resulting in a total of 37.056 patients. The young age group (⩽40 years) consisted of 1.102 (3%) patients, and the middle-aged group included 35.954 patients (97%). The median age at the time of diagnosis in the young group was 35.1 years, compared with 60.2 years in the middle-aged group. There were fewer males in the young age group compared with the

Discussion

Young rectal cancer patients are more likely to have advanced-stage disease, and their tumours exhibit unfavourable characteristics. Nevertheless, their survival rates are equal to those of middle-aged patients.

In the present study, young rectal cancer patients had more advanced stage of disease compared to middle-aged patients. This pattern has also been observed in other studies, in which younger patients were found to present with more advanced disease [6], [9], [10], [21]. As in the present

Conclusions

Young patients present with more advanced disease and less favourable tumour morphology compared with middle-aged patients. Despite these unfavourable characteristics, the survival rates in these groups are equal, and young age is even a prognostic factor for improved survival. Young patients received adjuvant chemotherapy more often compared with middle-aged patients, and treatment with chemotherapy was associated with improved survival in young patients with pN1 or stage III disease.

Conflict of interest statement

None declared.

References (33)

  • R. Glynne-Jones et al.

    Chronicle: results of a randomised phase III trial in locally advanced rectal cancer after neoadjuvant chemoradiation randomising postoperative adjuvant capecitabine plus oxaliplatin (XELOX) versus control

    Ann Oncol

    (2014)
  • A.J. Breugom et al.

    Adjuvant chemotherapy for rectal cancer patients treated with preoperative (chemo)radiotherapy and total mesorectal excision: a Dutch Colorectal Cancer Group (DCCG) randomized phase III trial

    Ann Oncol

    (2015)
  • C. Tiselius et al.

    Patients with rectal cancer receiving adjuvant chemotherapy have an increased survival: a population-based longitudinal study

    Ann Oncol

    (2013)
  • International Agency for Research on Cancer, Globocan 2012....
  • IKNL Cijfers over kanker. <http://www.cijfersoverkanker.nl/p=54845cc3c08f5> accessed 12-7-2014;...
  • J.E. Meyer et al.

    Increasing incidence of rectal cancer in patients aged younger than 40 years: an analysis of the surveillance, epidemiology, and end results database

    Cancer

    (2010 Sep 15)
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