Does Non-Surgical Treatment (Watch and Wait) for Rectal Cancer Increase the Risk of Metastasis?

In rectal cancer treatment, a “watch and wait” approach may be used in some patients after neoadjuvant (tumor-shrinking) treatment, following which the tumor may shrink considerably or appear to disappear completely. However, some patients may develop local tumor regrowth over time. This means that the cancer becomes apparent again at its original site, the rectum. Local tumor regrowth develops when tumor cells have not been completely eradicated or remaining cells begin growing again.

Below is an illustration of a tumor in the rectum that appears to be at an early stage:

A Study Demonstrating the Importance of Timely Surgery

When local regrowth develops, the cancer becomes active again, and its potential to spread to distant organs—the risk of distant metastasis —increases. Delaying surgery in patients with local regrowth may therefore adversely affect distant metastasis-free survival.

A new study published on October 28, 2024, in Journal of Clinical Oncology (JCO) emphasizes the importance of timely surgery in improving distant metastasis-free survival rates.

What Is the Watch-and-Wait Approach in Rectal Cancer?

Watch and wait is an alternative to surgery in rectal cancer that supports organ-preservation strategies. In this approach, patients receive neoadjuvant treatment before surgery. Neoadjuvant treatment generally involves chemoradiotherapy or chemotherapy and aims to reduce the cancer's size so that it disappears completely or very few tumor cells remain. If a review of the patient's radiological and clinical findings after treatment suggests a complete clinical response , surgery may be avoided and a watch-and-wait protocol may be used.

Who Can Be Considered for Watch and Wait?

The watch-and-wait strategy is considered for patients with stage 2 or 3 disease at diagnosis whose tumors visibly shrink or disappear completely only after neoadjuvant treatment. However, oncology specialists carefully assess this decision using criteria such as tumor stage, the patient's overall health, age, and response to treatment. If assessments in patients with a complete clinical response conclude that the tumor can be monitored without surgery, these patients are spared surgery and closely followed at regular intervals.

How Are Patients Monitored During Watch and Wait?

Patients undergoing watch and wait enter a rigorous follow-up program to minimize the risk of recurrence (local regrowth). This generally includes regular endoscopic assessments, MRI scans , and biopsies . If local tumor regrowth is detected, the tumor is removed surgically.

Rationale and Importance of the Current Study

Organ-preservation strategies in rectal cancer have become an appealing alternative to surgery for patients who achieve a complete clinical response after neoadjuvant treatment. However, these patients have a risk of local tumor regrowth of approximately 25%-30% . Although watch and wait appeals particularly to patients seeking less invasive treatment, this also raises important questions about the risk of distant metastasis. The findings of the study discussed here aim specifically to determine how the timing of surgery affects distant metastasis risk.

Research Methods

This study aimed to compare patients with local tumor regrowth and those undergoing total mesorectal excision (TME) in terms of their risk of developing distant metastasis. It included 508 patients with local regrowth from the International Watch & Wait Database and 893 patients with a near-complete pathological response from the Spanish Rectal Cancer Project.

Total mesorectal excision (TME) is a procedure in rectal cancer surgery in which the entire rectum and surrounding mesorectal tissue, including all lymph nodes and fatty tissue, are removed. It is considered standard treatment for minimizing local cancer recurrence and improving long-term survival.

• Primary Objective: To assess 3-year distant metastasis-free survival rates after the decision to pursue watch and wait or TME.
• Secondary Objectives: To analyze potential risk factors associated with distant metastases.

Summary of Findings

The study found a significantly higher rate of distant metastasis in patients with local regrowth than in patients who underwent TME and had a near-complete pathological response. The numerical findings were as follows:

• The distant metastasis rate in patients with local regrowth was 22.8% , compared with 10.2% in those undergoing TME (P ≤0.001).

• The 3-year distant metastasis-free survival rate was 75% in patients with local regrowth and 87% in patients undergoing TME (P < 0.001).

The study identified three main factors that increased the risk of distant metastasis:

• Local Tumor Regrowth: Patients with local tumor regrowth had a significantly higher risk of distant metastasis than those undergoing TME (P = 0.001).
• Advanced Tumor Stage (ypT3-4): An advanced tumor stage (ypT3-4) on pathological examination after neoadjuvant treatment increases the risk of distant metastasis (P = 0.016).
• Lymph Node Involvement (ypN+): Patients with lymph node involvement have a higher risk of developing distant metastasis (P = 0.001).

In conclusion, patients with local tumor regrowth have lower distant metastasis-free survival rates than patients undergoing TME across all stages.

What Should We Take from This Study?

According to these findings, local tumor regrowth during a watch-and-wait strategy for rectal cancer can increase the risk of distant metastasis. However, this does not mean that watch and wait cannot be used at all. The watch-and-wait strategy may remain an important option, particularly for patients who want to avoid the adverse effects of surgery, have responded well to neoadjuvant treatment, and have a low tumor burden.

Deciding when surgery should be performed becomes critical as soon as local regrowth is observed. Because the study suggests that early surgery may reduce distant metastasis risk in these patients, performing surgery as soon as signs of regrowth appear may have a positive effect on survival.

Watch and wait may therefore remain an option for low-risk patients with a strong response to treatment . However, this strategy requires very close monitoring, regular imaging and biopsies, and a plan for prompt surgery at the first signs of tumor regrowth.

Study Limitations

The study has certain limitations, including differences between institutions in the definition of complete clinical response and variation in watch-and-wait decisions. Most patients also did not receive total neoadjuvant treatment regimens, which may limit the generalizability of the findings. Some patients were also lost to follow-up, potentially increasing the risk of bias.

Conclusion and Recommendations

Although watch and wait in patients with rectal cancer is promising in terms of distant metastasis risk when a complete clinical response is achieved, postponing surgery in cases of local regrowth may increase that risk. Carefully monitoring these patients and performing timely surgery when regrowth is observed are therefore critical to improving survival rates.