A Substantial Proportion of Locally Advanced Rectal Cancers Can Be Treated Directly by Surgery

Currently, the reference standard treatment for locally advanced rectal cancer, meaning tumours that have grown deeper into the layers of the rectal wall and/or involved nearby lymph nodes, but have not yet spread to the rest of the body – is to submit patients to chemotherapy and radiotherapy before surgery. This “total neoadjuvant therapy” reduces the risk of the cancer coming back in the rectum and can lower the risk of metastases, but has a cost for the patients because of the detrimental effects of radiation. 

Now, a study carried out by the Colorectal surgery team at the Champalimaud Foundation, in Lisbon, with colorectal surgeon Laura Fernandez as the first author, has shown that neoadjuvant therapy may not be necessary for a substantial number of patients with locally advanced tumours in Stages II and III (respectively without and with nearby lymph node involvement). More to the point, using high-resolution magnetic resonance imaging (MRI), it is possible to identify additional important risk factors and, within this group of patients, distinguish a lower-risk subgroup that is unlikely to benefit from treatment before surgery. For these carefully selected patients surgery can safely be performed as the first step. Their results were very recently published in the journal Diseases of the Colon & Rectum.

The surgery referred to in this study is “total mesorectal excision” (TME), the gold-standard surgical treatment for rectal cancer worldwide. It involves the complete removal of the rectum, surrounding fat (mesorectum) and surrounding lymph nodes as a block. It was developed in 1982 by British surgeon Bill Heald, who has been Chairman of the Colorectal Cancer Programme at the Champalimaud Foundation for over 10 years.

Fernández and the team wanted to know whether patients in stages II and III of rectal cancer that were considered as being at low risk for local recurrence and metastases, could be submitted directly to TME, avoiding preoperative treatment. Specifically, these were patients whose MRI showed that the mesorectal fascia – the capsule of fibrous tissue that envelops the mesorectum – was clear of the disease.

For this, they used an existing database at the Champalimaud Foundation that includes patients with clinical stage II and III rectal adenocarcinoma who had surgery without preoperative radiochemotherapy between 2013 and 2024. In total, 94 patients showed a clear mesorectal fascia on their MRI and were submitted to surgery upfront. More than 95% of these operations were performed using minimally invasive techniques, with over 75% carried out with robotic surgery, which is currently the standard approach within the team. The surgical program was developed following dedicated training of the team by senior co-author Amjad Parvaiz.
 
The clinical outcomes for these 94 patients were “excellent”, according to the authors. All patients were free of local recurrence after three years, and more than 95% after five years. Eighty-seven percent were free of distant metastasis after three years and 81% after 5 years. The overall survival rate at three years was 97% and about 95% at five years.

“Patients who underwent upfront surgery with high-quality total mesorectal excision as identified by high-resolution MRI achieved excellent oncological outcomes, making neoadjuvant therapy unnecessary in a subset of stage II/III rectal cancers with clear mesorectal fascia”, the authors write.

“Additional studies could help answer the question of whether upfront surgery should now be included as a standard option in contemporary rectal cancer trials”, they point out.

What about treatment after surgery?

Of note is that, after surgery, based on the final histological staging of these patients’ disease, only half of them were submitted to postoperative chemotherapy, because the TME was considered to have successfully removed all of the cancer. Therefore, a further result of the study is that the other half were treated with surgery alone.

Nonetheless, the authors remark that this last finding “must be interpreted with caution, acknowledging that all stage III patients in our cohort received adjuvant therapy and that [post-operative] systemic treatment remains a key component” of the therapy for some patients.

But ultimately, they speculate, one could expect that a significant proportion of patients with stage II or III rectal cancer could also have been spared from unnecessary postoperative chemotherapy and been treated with surgery alone. 

“Although these outcomes are promising, further research in larger, multicenter studies with longer follow-up is needed to validate these findings and refine patient selection criteria”, they conclude.

The original paper can be read here.

Text by Ana Gerschenfeld, Health&Science Writer of the Champalimaud Foundation.