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Determinants of Pre-Surgical Treatment in Primary Rectal Cancer: A Population-Based Study
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Cancer precision medicine.ORCID iD: 0000-0002-0232-2391
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Cancer precision medicine.ORCID iD: 0000-0002-8271-2241
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Cancer precision medicine.ORCID iD: 0000-0002-5440-791x
2023 (English)In: Cancers, ISSN 2072-6694, Vol. 15, no 4, article id 1154Article in journal (Refereed) Published
Abstract [en]

Simple Summary Preoperative radiotherapy has an established role in the treatment of rectal cancer, alone or with chemotherapy, but the use varies considerably. Many scientists have strived to reduce the use of radiation while maintaining high local control rates, partly counterbalanced by an ambition to preserve the organ. Besides patient-related factors, stage as defined by magnetic resonance imaging (MRI) is most important for the decision at multidisciplinary team (MDT) conferences to recommend direct surgery or any treatment prior to (eventual) surgery. In a large prospective, unselected and properly staged patient cohort, MRI characteristics were most important for treatment selection, but patient-related factors were also relevant. Changes over time, reflecting changed national guidelines that were striving to reduce the use of radiation, were seen; however, they were probably interpreted differently in the two analysed regions. The accuracy of MRI evaluated by specially trained radiologists, during an MDT conference in real life, was poor. When preoperative radiotherapy (RT) is best used in rectal cancer is subject to discussions and guidelines differ. To understand the selection mechanisms, we analysed treatment decisions in all patients diagnosed between 2010-2020 in two Swedish regions (Uppsala with a RT department and Dalarna without). Information on staging and treatment (direct surgery, short-course RT, or combinations of RT/chemotherapy) in the Swedish Colorectal Cancer Registry were used. Staging magnetic resonance imaging (MRI) permitted a division into risk groups, according to national guidelines. Logistic regression explored associations between baseline characteristics and treatment, while Cohen's kappa tested congruence between clinical and pathologic stages. A total of 1150 patients without synchronous metastases were analysed. Patients from Dalarna were older, had less advanced tumours and were pre-treated less often (52% vs. 63%, p < 0.001). All MRI characteristics (T-/N-stage, MRF, EMVI) and tumour levels were important for treatment choice. Age affected if chemotherapy was added. The correlation between clinical and pathological T-stage was fair/moderate and poor for N-stage. The MRI-based risk grouping influenced treatment choice the most. Since the risk grouping was modified to diminish the pre-treated proportion, fewer patients were irradiated with time. MRI staging is far from optimal. A stronger wish to decrease irradiation may explain why fewer patients from Dalarna were irradiated, but inequality in health care cannot be ruled out.

Place, publisher, year, edition, pages
MDPI, 2023. Vol. 15, no 4, article id 1154
Keywords [en]
rectal cancer, radiotherapy, chemoradiotherapy, preoperative therapy, neoadjuvant therapy, magnetic resonance imaging, treatment guidelines, population-based
National Category
Surgery Radiology, Nuclear Medicine and Medical Imaging
Identifiers
URN: urn:nbn:se:uu:diva-499161DOI: 10.3390/cancers15041154ISI: 000938409600001PubMedID: 36831497OAI: oai:DiVA.org:uu-499161DiVA, id: diva2:1747926
Funder
Swedish Cancer Society, 190382PJ01HAvailable from: 2023-03-31 Created: 2023-03-31 Last updated: 2025-10-14Bibliographically approved
In thesis
1. Rectal Cancer Treatment and Response Prediction
Open this publication in new window or tab >>Rectal Cancer Treatment and Response Prediction
2025 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Rectal cancer is one of the most common cancers in Sweden with 2000 new cases annually. Outcomes have improved over recent decades due to better staging, using magnetic resonance imaging (MRI), refined surgical techniques and optimised use of radiotherapy (RT) or chemoradiotherapy (CRT). More recently, total neoadjuvant therapy (TNT), RT/CRT and chemotherapy before surgery, has emerged as a superior treatment for locally advanced rectal cancers (LARC). Rectal cancers are stratified into risk groups for systemic and loco-regional recurrence (LRR), requiring different treatments. Response to neoadjuvant therapy varies considerably between tumours, and despite extensive research, reliable predictors of response remain to be identified. The LARCT-US study treated LARC patients with TNT; 5x5 Gy + 4 CAPOX, an abbreviated RAPIDO-schedule. The aim of this thesis was to explore factors of importance for treatment choice and outcome in rectal cancer patients.

Paper I assessed the neoadjuvant rectal (NAR) score, a short-term surrogate endpoint to compare different regimens in clinical trials. The NAR-score discriminated between different treatments having different cytotoxic effects and applies irrespective of therapy given.

Paper II describes treatment selection over time in an unselected patient cohort from two adjacent Swedish regions. MRI-based risk grouping most strongly influenced treatment choice, with fewer patients receiving RT over time. Variations in MRI-interpretation and a stronger desire to decrease RT may explain regional differences. Accuracy of MRI was poor and requires improvement.

Paper III investigated long-term outcome and recurrence predictors in LARCT-US. The TNT schedule achieved excellent systemic control (25%) and few LRR (6%). The low LRR risk compared with RAPIDO may reflect more adequate distal resection margins practiced at Swedish centres. Besides treatment response, multiple high risk-criteria, tumour deposits, low tumour level and a sub-optimal resection plane were associated with recurrence risk.

Paper IV evaluates quality of life (QoL) and late toxicity following LARCT-US. QoL was comparable to that in the RAPIDO TNT-arm. Major bowel dysfunction was less frequent (45% vs 59%). Grade 3+ late toxicity occurred in 12% at three years and 8% at five years. Overall, the abbreviated TNT schedule achieves favourable oncological outcomes with acceptable QoL and limited late toxicity.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2025. p. 58
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 2200
Keywords
Rectal cancer, Neoadjuvant treatment, Radiotherapy, Chemoradiotherapy, Total neoadjuvant therapy, Treatment response, Long-term outcome, Quality of life.
National Category
Medical and Health Sciences Clinical Medicine Cancer and Oncology Surgery
Research subject
Medical Science
Identifiers
urn:nbn:se:uu:diva-568340 (URN)978-91-513-2630-6 (ISBN)
Public defence
2025-12-04, Rudbecksalen, Rudbecklaboratoriet, Dag Hammarskjölds väg 20, 751 85, Uppsala, 09:00 (English)
Opponent
Supervisors
Available from: 2025-11-07 Created: 2025-10-14 Last updated: 2025-11-07

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Imam, IsraaHammarström, KlaraGlimelius, Bengt

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