In rectal cancer management, the main application of radiotherapy (RT) is in the neoadjuvant setting in Stage III (T3-4, node positive) and selected Stage II cancers.
A multidisciplinary approach is imperative to ensure all patients and cancer factors are carefully discussed. The American Society for Radiation Oncology (ASTRO) practice guidelines recommend that surgery occurs within 6-11 weeks post chemo radiation.
There is evidence of increasing perioperative complications between 7-11 weeks, but strong evidence in favour of a higher pathological complete response (pCR) rate if the surgical interval post chemoradiation is over six weeks. For short-course radiotherapy patients, an interval before surgery of less than three days or 4-8 weeks is recommended.
The common RT fractionation schedule is 50-50.4Gy in 25-28 fractions over 5-6 weeks (long-course), and 25Gy in five fractions (short-course). Long-course chemo radiation is commonly utilised over short-course RT, as recommended by the St Gallen European Organisation Research and Treatment of Cancer (EORTC) panel.
It is also generally advised if the circumferential resection margin and/or the margin resection status is likely to be compromised. Recent ASTRO clinical practice guidelines support both long-course and short-course RT in patients requiring neoadjuvant therapy. Randomised studies suggest similar efficacy and patient-reported quality of life outcomes with either approach.
Interest is increasing towards a total neoadjuvant therapy (TNT) approach. Total neoadjuvant therapy involves the delivery upfront of multi-agent chemotherapy then chemoradiation followed by definitive surgery. The rationale of TNT is to induce a higher rate of pCR, and hence improved downstaging. It is also possibly better tolerated compared to the standard approach.
However, despite reports of enhanced disease-free survival, an overall survival benefit with TNT is not yet proven. Several trials have investigated different TNT approaches and their benefits.
The option of ‘watchful waiting’ or non-operative management is also gaining interest in patients who achieve a complete clinical response (cCR), as most patients would understandably prefer to avoid surgery or a stoma. However, surgery remains the definitive treatment for cure.
Watchful waiting is feasible in a selected cohort of patients under multidisciplinary management if they are compliant with regular surveillance and investigations aimed at ruling out recurrence or enabling early salvage treatment. In a meta-analysis, the only risk factor associated with regrowth was the initial T stage. A distant metastasis rate of 5% to 9% has also been reported with watchful waiting. The TNT approach may allow a larger proportion of patients to undergo watchful waiting within a carefully shared decision-making process.
The frequency and modality of investigations remains variable from institution to institution. Response is assessed typically 2-3 months after treatment and the definition of cCR is based on clinical examination: digital rectal examination (DRE), endoscopic features, and imaging studies, specifically rectal MRI.
As tumour regrowth is most frequent in the first two years after radiotherapy, current protocols recommend DRE and flexible sigmoidoscopy every three months for the first two years and then every 6-12 months for the next three years. These patients also require surveillance CT chest, abdomen, and pelvis every 6-12 months for the first two years, and then annually to rule out the development of distant metastases.
RT is also useful in the treatment of Stage IV colorectal cancers with either aggressive intent in the oligometastatic setting (under five sites of metastatic disease), or with palliative intent to relieve symptoms, such as bleeding or pain. The recent COMET-SABR trial supports the use of stereotactic body radiotherapy (SBRT) to metastatic tumours in oligometastatic disease due to improved progression-free survival and median overall survival (50 vs 28 months).
Radiation techniques have greatly evolved in recent decades. RT is now delivered in a modulated technique with either intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc therapy (VMAT). Such techniques enhance conformity and enable dose to be maximised to the target while minimising its delivery to surrounding organs, such as the bladder, sexual organs, normal bowel, and pelvic bones.
This has been shown to reduce the incidence of acute and late toxicities, particularly in the bowel.
Radiation oncology has made great progress in the last decade. In colorectal cancer, RT remains an important part of the multidisciplinary armamentarium. Our challenge now as clinicians and researchers is to continually advance and improve treatment techniques to maximise the equally important patient-reported outcomes.
Key messages
- A multidisciplinary approach to management is key
- Interest in total neo-adjuvant treatment (TNT) is growing
- Radiation techniques have greatly evolved in the last decade.
– References available on request
Author competing interests – nil