Is Surgery Essential in Rectal Cancer?

Rectal Cancer at a Glance

• The large bowel is the final part of the gastrointestinal tract and measures approximately 1.5 meters. It has two main sections: the colon and rectum.

• The rectum follows the colon and forms its final 15 cm. Rectal cancers account for approximately 30% of colorectal cancers.

• Rectal cancers differ significantly in anatomy, biology and treatment.

• Surgery is the main treatment for early-stage rectal cancer.

• The rectum's proximity to the anus has prompted intensive research into preoperative tumor-shrinking approaches such as neoadjuvant treatment and nonsurgical treatment options for tumors in this area.

The illustration below shows the basic anatomy of the colon and rectum.

Can Rectal Cancer Be Managed Without Surgery?

Approximately 60-80% of patients have stage II or III disease when rectal cancer is diagnosed. This is called locally advanced rectal cancer.

Locally advanced rectal cancer affects the rectum and surrounding area but has not spread to distant organs. It is generally classified as stage II or III.

Research shows that stage II and III patients achieving a complete response to neoadjuvant treatment can be followed without surgery.

• At stage 2, cancer has spread to the rectum's outer layer or surrounding tissues but not the lymph nodes (T3-T4a N0).
• At stage 3, cancer has spread from the rectum into surrounding tissues and nearby lymph nodes (T1-T4a N1-N2).

Why Neoadjuvant Treatment Matters

Neoadjuvant treatment is given before surgery to shrink the tumor, improve surgical effectiveness and reduce the risk of spread. It is particularly important in locally advanced rectal cancer because it can:

• Shrink the Tumor: A smaller tumor allows clearer surgical margins and more successful resection.
• Improve Local Control: Reduce the risk of local recurrence.
• Preserve the Organ: Particularly in rectal cancer, neoadjuvant treatment may help preserve the rectum and improve quality of life.

Total Neoadjuvant Therapy (TNT)

Total neoadjuvant therapy (TNT) is a complete regimen of chemotherapy and radiotherapy before surgery. It aims for the greatest possible tumor shrinkage and local disease control before removal. Its goals are to make the tumor operable, prevent progression and potentially improve long-term outcomes.

It may consist of induction chemotherapy followed by chemoradiation (INKT-KRT), or chemoradiation followed by consolidation chemotherapy (KRT-KNKT).

Complete Response to Total Neoadjuvant Therapy

A complete response means the tumor becomes clinically undetectable after treatment: examination, including digital rectal examination, endoscopy and imaging when needed, no longer detects it. This does not necessarily mean all tumor cells have been eliminated, only that current diagnostic tools find no sign of tumor. Some patients may then be managed by surveillance alone, but suitability depends on a detailed assessment of overall health and response.

Complete clinical response rates vary between studies and protocols. Generally, after total neoadjuvant therapy, complete clinical response rates range from 20% to 30% .

The OPRA Study

The phase II OPRA study treated 324 patients with locally advanced (stage 2 and 3) rectal cancer using TNT. Complete clinical responders entered surveillance, while those with incomplete responses were offered total mesorectal excision (TME).

• Patients with stage II/III rectal cancer were randomized to two groups:

  • One received induction chemotherapy followed by chemoradiation (INKT-KRT).
  • The other received chemoradiation followed by consolidation chemotherapy (KRT-KNKT).

• Patients with complete or near-complete responses after treatment were offered watch-and-wait (WW). Nonresponders were offered total mesorectal excision (TME).

• There were 324 patients: 158 in INKT-KRT and 166 in KRT-KNKT.

• Median follow-up was 5.1 years.

• Five-year disease-free survival rates:

  • INKT-KRT: 71% (confidence interval 64% to 79%)
  • KRT-KNKT: 69% (confidence interval 62% to 77%)

• TME-Free Survival Rates:

  • INKT-KRT: 39% (confidence interval 32% to 48%)
  • KRT-KNKT: 54% (confidence interval 46% to 62%)

• Among 81 patients with tumor regrowth, 94% experienced it within the first 2 years and 99% within the first 3 years.

• The key finding: Complete clinical responders entering surveillance who later needed surgery for regrowth had the same five-year disease-free survival (64%) as patients operated on immediately when treatment began.

• Long-term organ preservation was achieved in 50% of patients treated with total neoadjuvant therapy. In the watch-and-wait group, regrowth occurred mainly within the first 2 years.

Risks and Benefits

Other studies of complete clinical responders after NAT also show high organ preservation rates with surveillance and disease-free survival comparable to surgery. However, local regrowth may occur in one third, and in some studies it increased the risk of metastatic disease and reduced overall survival.

Two points deserve particular emphasis:

• Local Tumor Regrowth: Local regrowth was seen in approximately 30% of patients under surveillance. In most (99%), it occurred within the first three years after treatment.
• Metastasis Risk: Patients under surveillance whose tumors regrow have a higher risk of metastatic disease than those without regrowth.

Conclusion

Current research suggests that nonsurgical management can be safe in appropriate centers for patients achieving a complete clinical response after total neoadjuvant therapy. The approach nevertheless requires caution because some patients face regrowth and metastatic disease. Regular follow-up by an experienced multidisciplinary team is vital to successful watch-and-wait management.