Long-course radiotherapy is better than short-course for organ preservation in rectal cancer

The COVID-19 pandemic has enabled researchers to show that a long course of radiotherapy given before surgery may be a better treatment for avoiding surgery, preserving the rectum and anus, and preventing regrowth of the primary tumour than a short course of radiotherapy for patients with rectal cancer – a type of bowel cancer. However, the overall survival and survival free of recurrence of the disease remained the same for both treatments.

These findings are from a new study published in the leading cancer journal Annals of Oncology [1] today (Thursday), and the researchers say that they “fill a crucial knowledge gap” about which treatment is better for preserving these important organs. This can make a real difference to patients’ quality of life because, if part of the bowel or anus needs to be removed during surgery to eradicate the tumour, some patients are fitted with a stoma or colostomy (a hole in the abdominal wall that connects to the bowel) through which faeces pass into a disposable bag worn over the hole.

Dr Paul Romesser, director of colorectal anal cancer radiation oncology at Memorial Sloan Kettering Cancer Center, New York, USA, who co-led the study with Dr J. Joshua Smith, associate attending surgeon at MSK, said: “The COVID pandemic, particularly intense in New York, forced us to re-evaluate resource allocation and treatment options to protect patients and staff by shortening the time they were exposed to each other. This led us to mandate that all rectal cancer patients be treated with short-course radiotherapy, SCRT, without exception, based on evidence from multiple prospective trials showing similar outcomes.

“The crucial knowledge gaps were whether organ preservation is safe after SCRT and which radiation treatment is best if organ preservation is the goal. Until now, there were no studies comparing SCRT and long course of chemoradiotherapy, LCCRT, in terms of organ preservation and local regrowth rates. Our study is the first to address both, finding that organ preservation by avoiding surgery after neoadjuvant SCRT is safe and may be preferred for some patients due to the convenience of treatment. However, the tumour regrowth rate was higher, necessitating close monitoring. If time and convenience aren’t factors, LCCRT appears to offer more durable organ preservation.”

The COVID pandemic enabled the researchers to create a “natural” experiment to compare the two forms of treatment, rather than conducting a randomised controlled trial. The study included 323 patients with locally advanced rectal cancer (cancer that had grown outside the rectum but had not yet spread to other parts of the body) who were treated with either SCRT or LCCRT as a neoadjuvant therapy to shrink the tumour before surgery between January 2020 and January 2021. If they were treated between March and June 2020 and between November 2020 and January 2021, they received SCRT (76 patients). Outside these periods, patients were treated with LCCRT (247 patients). Both groups of patients also received chemotherapy as well.

Patients who achieved a clinical complete response, meaning the tumour was no longer detectable, were offered “watch and wait” management instead of surgery, involving close monitoring during follow-up. Those who achieved a near complete response were re-evaluated in 6-12 weeks to allow additional time for their tumours to respond and if they then had a complete response, they were also offered “watch and wait” management. Patients with residual tumour, and those who declined “watch and wait”, underwent surgery to remove the rectum, the fatty tissue, lymph nodes and blood vessels around it to reduce the chances of the tumour coming back (this procedure is called a total mesorectal excision).

After an average (median) of 31 months, 44.5% of patients receiving LCCRT and 43.4% of patients receiving SCRT had a complete response. After two years, organ preservation was achieved in 40% of LCCRT and 31% of SCRT patients. In patients managed with “watch and wait”, LCRT resulted in higher organ preservation at two years (89% versus 70% in SCRT patients) and lower local regrowth (19% versus 36% respectively).

Recurrences of cancer in other parts of the body, disease free survival and overall survival were similar in “watch and wait” patients treated with LCCRT or SCRT: 10% versus 6.1%, 90% versus 90%, and 99% versus 100%, respectively.

Dr Smith said: “Our study also included information on patient-reported outcomes, which highlighted that patients who achieved organ preservation had good bowel function after both LCCRT and SCRT. The lack of differences in distant cancer recurrences, disease-free survival, and overall survival rates between the two groups is reassuring. It highlights the safety of integrating a ‘watch-and-wait approach’ into a neoadjuvant treatment strategy and the ability to treat patients successfully if local regrowth occurs. Most local regrowths can be detected with flexible endoscopies and occur in the first two years after completion of all treatment, underscoring the importance of close surveillance during “watch and wait. 

 “Despite similar clinical complete response rates, we observed more local regrowth after SCRT than LCCRT. This suggests that SCRT may be less durable than LCCRT. If the goal is lifelong organ preservation, LCCRT seems to be the preferred treatment option given our findings of more durable response with LCCRT.

“Given the rising incidence of rectal cancer in young adults it is critical to think about personalising treatments. There are times where patients with a clinical complete response undergo life-changing surgery only to find that no cancer was found in the surgical specimen. Patients and providers alike should be questioning the utility of surgery in settings such as this. The goal should be personalised treatment to maintain cure rates but avoid over-treatment.”

Dr Romesser said: “It’s important to stress that both treatments remain good options for patients, especially as overall survival is the same. There are situations where LCCRT is just not feasible and presents a burden to the patient and their family due to the frequent visits to hospital over a long period of time to receive the radiation therapy. In these circumstances, our data provide the support that organ preservation after SCRT is safe and feasible. They also help healthcare providers to understand patients treated with SCRT have a higher risk of local regrowth within the first two years. While organ preservation can be achieved after both SCRT and LCCRT, if the goal is an optimised approach, I’d recommend LCCRT followed by consolidative chemotherapy before surgery.”

The researchers will continue to monitor the patients to see how they do over a longer term of five to seven years.

“Our ultimate goal is personalised therapy based on the patient, the patient’s tumour genetics, and the goals of treatment. We are working to develop biomarkers that can predict response to LCCRT and SCRT. It is likely that some patients will do better or just as well with SCRT, whereas others need LCCRT. Instead of a cookie cutter approach our research is focused on optimising treatment for an individual patient and tumour,” concluded Dr Romesser.

Darth Ann Clurman, aged 48, a teacher who lives near Sacramento, California, USA, was told by general practitioners that she was too young to have bowel cancer.

“I was diagnosed in August of 2022 after having my symptoms dismissed with ‘you're too young’ and ‘you had two natural childbirths, it's probably haemorrhoids’ by three GPs who talked to me virtually. I was 46 when I was diagnosed with a 3-4 cm, mid-low, flat rectal tumour,” she said.

An MRI scan showed the tumour was advanced, having spread into the pelvic floor muscle but with no cancer in the lymph nodes (T4N0). At Kaiser Permanente’s Roseville and Rancho Cordova hospitals, she was treated with long-course chemoradiotherapy (LCCRT), which eradicated all signs of the cancer, so she was able to avoid surgery and has been on ‘watch and wait’ since June 2023.

“I had eight sessions of chemo, followed three weeks later by 28 sessions of radiation with capecitabine. Intravenous chemo was tolerable for me. Radiation was brutal for the last two-and-a-half weeks and for two weeks after. I had persistent burning bowel movements, despite diet adjustments and creams. 

“I have a wonderfully supportive family, husband and siblings, that helped me get through treatment. I am extremely grateful for this non-operative pathway because of how common lower anterior resection syndrome is after reconnection from low tumours. I would have to change careers if I had urgency or incontinence. I'm especially happy with my surgeon at Kaiser Roseville for his knowledge of ‘watch and wait’, his close surveillance, and his excellent communication.”