Rectal cancer: towards better tolerated and more effective treatments

Rectal cancer towards better tolerated and more effective treatments

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    Rectal cancer is cancer that affects the end of the large intestine above the anus. Its treatment depends on its state of progress during the diagnosis. Today, two studies make it possible to lighten its management for the early and locally advanced stages for a better quality of life for patients and at least as good efficacy.

    Rectal cancer is a disease of the cells that line the inside of the rectum. It develops from an initially normal cell which transforms and multiplies in an anarchic way, until it forms a mass called a malignant tumor (or cancer). Two studies presented at the ASCO 2023 international congress on cancer will change its management.

    Some early cancers may avoid radiotherapy

    Advances in the treatment and early detection of colorectal cancer have resulted in steadily decreasing mortality rates, with the 5-year relative survival rate for locally advanced rectal cancer being 74%. Despite falling mortality rates, the incidence is increasing in younger patients.

    The reference treatment in this case is based on the combination of chemotherapy and radiotherapy before surgery. But these two treatments are not without side effects:

    • Radiation therapy can have significant short- and long-term toxicities that negatively impact quality of life, including infertility, ovarian failure, need for a temporary stoma, diarrhea, cramps, faecal incontinence and bladder problems;
    • Chemotherapy also has side effects, including fatigue, nausea, vomiting, low white blood cell count, infection, and neuropathy (numbness and tingling in the hands and feet).

    The researchers therefore wanted to see whether in these patients with a good prognosis, it was possible to save on radiotherapy before surgery. They compared two groups:

    The control group received the standard course of chemoradiotherapy (a combination of radiotherapy and 5FU or capecitabine) before surgery;

    The experimental group received the chemotherapy combination mFOLFOX6. If the tumor responded well to mFOLFOX6 and shrunk by 20% or more, patients were immediately operated on. If the tumor did not shrink by 20% or more or the patient could not continue with mFOLFOX6, they received the same chemoradiation as the control group before surgery (this will only affect 9% of patients in this band).

    After five years of follow-up, there was no difference between the two groups regarding overall survival, local recurrence rate, success of surgery…”

    The results of this study allow us to do just that, showing that we can omit radiation therapy for some patients, improving quality of life without compromising efficacy. These practice-changing results are important, even as the landscape of treating these patients continues to evolve.“says Prof. Pamela L. Kunz, ASCO expert.

    Principal author of the study, Pr. Deb Schrag, president of the department of medicine of the Memorial Sloan Kettering Cancer Center underlines the advantages of this study which can immediately change practices: “Firstly, in many regions of the world, radiotherapy is not readily available. An all-chemotherapeutic approach can make treatment with curative intent accessible to patients in these resource-limited settings. Additionally, given the increasing rates of colorectal cancer in young patients, this provides an option for patients who wish to preserve their fertility or avoid premature menopause”.

    A change in standards for locally advanced cancers

    For locally advanced rectal cancers (stage II and III), treatment could also evolve thanks to a French study. Unlike the traditional strategy consisting in chemotherapy being entirely carried out after the operation, the Prodige-23 study tested a new protocol with half of the chemotherapy being carried out before the operation, and the other half after. The total duration of treatment remains the same, but the order of treatment has been modified, and the preoperative chemotherapy reinforced (4 anti-cancer agents instead of 3). The 7-year results were presented at the ASCO 2023 congress, after encouraging 3-year results. Result: all the results are better with chemotherapy treatment distributed before and after surgery. The increase in 5-year survival was 7.6% for disease, 6.9% for overall survival, 9.9% for metastasis-free survival, and fewer locoregional relapses within 7 years (5.3 % versus 8.1%).

    Tolerance to postoperative chemotherapy was also better with less neurotoxicity. For patients with a recent diagnosis of locally advanced rectal cancer (stages II or III), this new treatment strategy should therefore become the new standard.

    We see that the management of rectal cancers is evolving towards better personalization of treatments according to the degree of progression of the disease. So that patients can benefit from these latest techniques, specialists recommend that patients prefer treatment in expert centres, where they can benefit from the latest treatments and be offered participation in clinical trials.

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