Precision cancer therapy for early-stage colorectal cancer: An expert's guide

Many cancers of the large bowel, which includes those in the colon and the rectum, are diagnosed when the tumour is localised and has not formed distant metastases. The treatment of such early-stage colorectal cancers is highly multidisciplinary; after having biopsies to establish the diagnosis and scans of the chest, abdomen and pelvis, treatment sometimes includes radiotherapy to shrink the tumour, and in most cases surgery to remove the tumour. Several months of chemotherapy may be necessary after surgery to reduce the risk of the tumour coming back. A long-term cure is the ultimate aim of these complex treatments. In his latest online article, renowned consultant medical oncologist Professor Marco Gerlinger explains everything you need to know about these treatment options.

How does precision cancer therapy differ from conventional cancer treatment?

The latest precision cancer therapies use advanced molecular and imaging tests to determine the best treatment for each individual cancer. The aim is to increase the chance of curing the cancer, minimise long-term side effects and improve the quality of life for patients. Precision treatment may also incorporate some of the latest targeted drugs.     

How is precision cancer therapy being used to improve clinical outcomes in patients with localised colorectal cancer?

One recent major improvement is the introduction of circulating tumour DNA blood tests that can detect micro-metastases with high sensitivity. If the ctDNA test shows no evidence of residual cancer in a patient who had surgery for a high-risk stage 2 colorectal cancer, it is safe not to give chemotherapy based on clinical trial results. Oncologists can then avoid overtreating such patients with unnecessary chemotherapy. This shortens the overall treatment by 3-6 months and patients who just had surgery can get back to their normal life much quicker. It also prevents long-term neuropathy which occurs as a side-effect of chemotherapy in 10-20% of patients.

Another example is the use of total neoadjuvant therapy (TNT) in locally advanced rectal cancers. These tumours have traditionally been treated with a sequence of radiotherapy, then surgery and finally chemotherapy. Recent trials showed that TNT, which gives chemotherapy and radiotherapy before surgery, can achieve better results. TNT has a higher complete response rate and the approximately 20% of patients who have such an excellent response may not need surgery. They can instead be followed by regular endoscopy and MRI scans and only have surgery if a regrowth of the cancer is detected.

A final example of an emerging precision cancer treatment is immunotherapy instead of surgery, chemotherapy and radiotherapy for the treatment of mismatch repair deficient rectal cancers (also called dMMR or MSI tumours). A small study showed complete responses in all 12 patients who received this treatment. Despite the small number of patients in the trial, this has already been included in clinical management guidelines in some regions. Although further research is needed, immunotherapy appears to make surgery unnecessary in the majority of patients with this rectal cancer subtype. This means there is no need for a permanent stoma, or for radiotherapy which can for example cause infertility.

What are the challenges of using precision medicine to treat localized rectal cancer?

Precision cancer therapy requires even closer teamwork of different specialties than in the past. Frequent multidisciplinary meetings are for example necessary to determine which one of a rapidly growing number of tests and treatment approaches is best for each patient. Furthermore, advanced molecular tests or novel drugs are not yet available everywhere or may not be funded by insurance companies. However, the oncology community is driving these changes forward to get smarter treatments to our patients.  

What are the future directions of research in precision medicine for early-stage colorectal cancer?

There are several unanswered questions which are being looked at in clinical trials. For example, whether or not we can also omit adjuvant chemotherapy in patients who had surgery for stage 3 colorectal cancer and are ctDNA negative. These have a higher recurrence risk than high-risk stage 2 cancers and we currently don’t have enough data to show if a negative ctDNA blood test makes this a safe approach.

Several trials are also trying to work out which tumours should have chemotherapy, targeted therapies or even immunotherapy before surgery to shrink the tumour first. The aim here is to make surgery easier and less invasive and to improve survival by killing microscopic metastases as early as possible.

What are the ethical considerations surrounding precision cancer therapy for localised colorectal cancers?

Well-designed clinical trials are key for this. They are first of all approved by an ethics committee and they usually have multiple safety nets built in in case a new precision medicine intervention does not work as well as expected. The trials generate robust and detailed evidence about efficacy and side effects. This evidence base is critical to discuss the pros and cons of new precision therapeutics with patients so that they can decide which treatment fits best with their lifestyle and health priorities.

Professor Marco Gerlinger is a renowned consultant medical oncologist based in London. If you would like to book a consultation with Professor Gerlinger, you can do so today via his Top Doctors profile.