Outcomes of Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer: A Prospective Observational Real-World Cohort in Johannesburg, South Africa

For decades, the standard approach to treating a specific type of bowel cancer that has grown deep into the wall but has not spread to other organs involved a rigid sequence: radiation and chemotherapy first, followed by major surgery to remove the rectum. While this method successfully stopped the cancer from returning, it often came at a steep price. The surgery could leave patients with permanent changes to how they use the bathroom, difficulties with urination or sexual function, or the need for a permanent bag attached to the abdomen to collect waste. In recent years, doctors have begun to ask if there is a way to save the organ itself. If powerful drugs and radiation can shrink the tumor so completely that it disappears from view, perhaps the patient can avoid the knife altogether. This strategy, known as "watch and wait," involves monitoring the patient closely and only operating if the cancer shows signs of coming back.

To make this organ-saving approach work, researchers have developed a method called total neoadjuvant therapy. Instead of spreading treatment out over a long period with surgery in the middle, this approach delivers all the chemotherapy and radiation before any surgery is considered. The goal is to hit the cancer hard and early, giving it the best chance to vanish completely. While this strategy has been studied extensively in wealthy nations with advanced medical systems, it was unclear whether it could work in places where resources are tighter. In South Africa, a team of doctors at a private teaching hospital in Johannesburg decided to test this approach in their own community. They wanted to see if they could deliver this complex, multi-step treatment plan and achieve results that matched the high standards seen in international studies, all while trying to spare their patients from unnecessary surgery.

The researchers followed the journey of forty-six adults who had been diagnosed with locally advanced rectal cancer. These patients were treated between March 2022 and January 2026. Before any treatment began, a team of specialists reviewed each case to decide on a personalized plan. The treatment involved a combination of radiation therapy and strong chemotherapy drugs, delivered in a specific order. Some patients received the chemotherapy before the radiation, others after, and some received it on both sides of the radiation. The team used different types of radiation schedules and various drug combinations, but the core idea remained the same: treat everything first, then see what is left.

Once the treatment was finished, the doctors waited a few weeks and then performed a thorough check-up. They used digital exams, cameras to look inside the bowel, and detailed scans to see if any trace of the tumor remained. If the scans showed no sign of cancer, the patient was considered to have a "clinical complete response." These patients were offered the chance to skip the surgery and enter a strict surveillance program. If the cancer was still visible, or if it came back later, the patient would undergo the standard surgery to remove the rectum. The team tracked how many patients finished their treatment, how many avoided surgery, and how long they stayed cancer-free.

The results showed that this complex plan was highly feasible in this setting. Nearly all patients, about ninety-six percent, were able to complete their full course of treatment as planned. While some patients experienced side effects, severe reactions were relatively uncommon. The treatment worked well at shrinking the tumors. Almost half of the patients, twenty-one out of forty-six, achieved a complete disappearance of the cancer and were able to enter the watch-and-wait program without immediate surgery. For those who did undergo surgery, the doctors were able to remove the cancer with clear margins in every single case, meaning no cancer cells were left behind at the edges of the removed tissue.

However, the story of organ preservation was more complex than the initial success suggested. While nearly half the patients started the watch-and-wait program, the cancer returned in the rectum or nearby lymph nodes for about half of them over the next few years. By the end of the three-year follow-up period, only about eighteen percent of the entire group had managed to keep their rectum without needing surgery. This decline happened because the cancer grew back in some patients who had initially seemed cured. When this happened, the doctors performed "salvage surgery" to remove the regrown tumor. Crucially, this second surgery was also successful, with all patients who underwent it having the cancer completely removed. The overall survival rates for the group were strong, with eighty-seven percent of patients still alive three years after starting treatment, and seventy-six percent free of the disease.

The study concluded that delivering this modern, intensive treatment plan is possible and effective in a well-resourced South African setting. The team managed to achieve high completion rates and strong cancer control outcomes that compared favorably with major international trials. Yet, the data also highlighted a reality of the watch-and-wait approach: while it offers a chance to avoid surgery, it requires a very careful and continuous monitoring system. Because the cancer can return even after disappearing, patients must be ready to undergo surgery if the tumor reappears. The findings suggest that for this strategy to succeed, patients need access to high-quality imaging, expert doctors, and the ability to get surgery quickly if the cancer comes back. The study did not prove that this approach works for everyone, as the group was relatively small and drawn from a specific private hospital, but it demonstrated that with the right resources, this advanced care can be delivered successfully outside of wealthy nations.