Rectal Cancer: Start with Surgery or Chemoradiotherapy?

Around 39% of colorectal cancers arise in the rectum, the final approximately 12-15 cm of the large intestine. The rectal region differs from the colon in its anatomy, function and response to treatment. Approximately 35-40% of rectal cancers are at stage 2 or 3 when diagnosed. In these patients, preoperative chemoradiotherapy (CRT) is widely used and recommended to reduce the risk of cancer recurring in the rectal region after treatment. However, oncologists are increasingly concerned that this approach may lead to overtreatment. The main challenge is how best to identify patients who could do well with less intensive treatment.

• Stage II rectal cancer: At this stage, the tumor has spread through all layers of the rectal wall but has not spread to the lymph nodes.
• Stage III rectal cancer: At this stage, the tumor has spread to nearby lymph nodes but not to distant organs or tissues.

Differences Between Rectal and Colon Cancer

Rectal and colon cancers are similar in many ways, but they also have important differences in anatomy, biology and treatment response.

• Anatomical differences: The rectum lies in a confined space within the pelvis and has many sensitive surrounding structures, which can complicate surgery. The colon lies more freely within the abdominal cavity, with less sensitive surrounding structures.
• Biological differences: Rectal and colon cancers are generally associated with different genetic alterations. These differences may influence tumor growth, spread and response to treatment.
• Treatment response: Rectal cancers tend to respond better to radiotherapy than colon cancers. Neoadjuvant radiotherapy (given before surgery to shrink the tumor) is therefore often used for rectal cancer. Radiotherapy is generally not used to treat colon cancer.

Rectal cancer treatment is also more complex because of its functional consequences, which can lead to quality-of-life problems such as impaired bowel control after surgery. This plays an important role in evaluating treatment options and discussing them with patients.

A German team, writing in the Journal of Clinical Oncology on 19 June, recommends preoperative MRI (magnetic resonance imaging) to assess the tumor’s presence. In this approach, the tumor is removed directly by surgery if the mesorectal fascia (MRF) is unaffected, while patients with affected MRF need neoadjuvant (preoperative) chemoradiotherapy to shrink the tumor.

A Key Determinant of Rectal Cancer Treatment: Mesorectal Fascia (MRF) Involvement

Mesorectal fascia (MRF): The mesorectum is a layer of fatty tissue surrounding the rectum and containing much of its lymphatic drainage. The mesorectal fascia is the thin connective-tissue layer enclosing and defining this fat. Rectal cancer commonly spreads within the mesorectum, making the MRF critically important in treatment.

Total mesorectal excision (TME): TME is the gold-standard surgical procedure for rectal cancer. The surgeon completely removes the tumor and surrounding mesorectum within its enclosing mesorectal fascia. This prevents lymphatic tumor spread and reduces the risk of regional cancer recurrence.

The Importance of MRF in Stage II and Stage III Rectal Cancer

Whether the tumor has spread into the mesorectal fascia has a major influence on the course of rectal cancer and its treatment plan. Tumor involvement of the MRF generally indicates a worse disease course because it suggests the potential for more extensive spread through the lymphatic system.

During TME, the surgeon ideally aims to remove the tumor and MRF intact. If the tumor involves the MRF or the MRF is damaged during surgery, this is called “positive MRF” and is associated with a higher risk of regional recurrence. These patients therefore generally receive neoadjuvant chemoradiotherapy before surgery to help shrink the tumor and make the MRF negative.

Assessing MRF status is therefore very important for staging rectal cancer and developing the most appropriate treatment plan. Preoperative magnetic resonance imaging (MRI) is generally used. It helps doctors determine whether the tumor involves the MRF and thus identify the most suitable treatment options.

Who Can Avoid Chemoradiotherapy Based on MRI?

The paper discussed here evaluates MRI for assessing the tumor’s presence. In this approach, the tumor is removed by total mesorectal excision (TME) alone if the mesorectal fascia (MRF) is unaffected. Patients with affected MRF need neoadjuvant chemoradiotherapy to shrink the tumor.

This idea was tested in 884 patients with stage II-III rectal cancer. The 530 patients with clear MRF (60 percent) underwent total mesorectal excision directly. This group’s 5-year regional cancer recurrence rate was 2.9%.

Risk Classification by MRF Status in Rectal Cancer

The distance between the tumor and mesorectal fascia (MRF) is an important factor in rectal cancer treatment. Patients with a distance of 1 mm or more between the MRF and tumor are generally considered low risk. These patients are generally referred directly for surgery, such as total mesorectal excision (TME).

On the other hand, tumors within 1 mm or less of the MRF are considered high risk. Neoadjuvant chemoradiotherapy (radiation and chemotherapy before surgery) is generally recommended to shrink the tumor before surgery. This can reduce tumor size and extent, improve the success of surgery and reduce recurrence risk.

Study Results

The study included patients treated at 14 centers in Germany between 2007-2016.

The study results provide information on 5-year regional recurrence and distant metastasis rates in patients divided into risk groups:

• The regional recurrence rate was 2.9% for low-risk patients (those who underwent TME directly), and
• 5.7% for high-risk patients (those who received neoadjuvant chemoradiotherapy followed by TME).

For distant metastasis:

• The 5-year distant metastasis rate was 15.9% in low-risk patients, and
• 30.5% in high-risk patients at 5 years.

Overall, the study suggests that neoadjuvant chemoradiotherapy should be considered only for patients at high risk of regional recurrence.

Generalizability of Scientific Results and Applicability in the Community

This study supports recent research suggesting that many patients with rectal cancer are overtreated. The results and significant differences require substantial experience and expertise from both the cancer center and radiologists in identifying mesorectal fascia (MRF) involvement on MRI. This is critical for determining how far the MRF lies from the tumor and establishing the patient’s risk. Meanwhile, important recent research has examined another approach, “rectal cancer treatment without surgery,” which may perhaps become the most important treatment approach in the future.

There is currently a justified and important trend toward reducing the intensity of cancer treatment. Overtreatment can expose patients unnecessarily to side effects and waste healthcare resources. Every rectal cancer case should therefore be evaluated comprehensively at an experienced cancer center before treatment begins, with an optimal individualized treatment plan established. This evaluation should consider the patient’s medical condition, cancer stage, overall health and personal preferences.