Molecular Classification of Colorectal Cancer for Precision Treatment

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• Current Limitations of Colorectal Cancer Staging
• The New Molecular Taxonomy of Colon Cancer
• Impact on Prognosis and Treatment Selection
• The Future of Personalized Colorectal Cancer Therapy
• Looking Beyond Known Genetic Mutations
• Full Transcript

Current Limitations of Colorectal Cancer Staging

Dr. Hans-Joachim Schmoll, MD, highlights a critical gap in current colorectal cancer care. The existing anatomic and histological staging system fails to differentiate between patients within the same stage. Dr. Hans-Joachim Schmoll, MD, explains that we lack methods to distinguish stage II colon cancer patients from one another. The same is true for patients diagnosed with stage III colon cancer.

This means clinicians cannot predict an individual's expected prognosis accurately. They also cannot forecast how a specific patient will respond to chemotherapy. This one-size-fits-all approach leads to overtreatment for some and undertreatment for others. Dr. Anton Titov, MD, discusses these significant clinical challenges with Dr. Hans-Joachim Schmoll, MD.

The New Molecular Taxonomy of Colon Cancer

Precision medicine is advancing through a new molecular classification of colorectal cancer. Dr. Hans-Joachim Schmoll, MD, states that colon cancer will be divided into five or six distinct molecular subtypes. This new taxonomy is based on comprehensive molecular characterization of the tumor.

Third-generation sequencing technologies and multiple molecular methods enable this detailed profiling. Dr. Hans-Joachim Schmoll, MD, notes that a consortium of experts decides on this new classification system. The taxonomy primarily uses data from patients with resectable stage II and stage III colon cancers. This new system aims to include many more patient groups than the current classification allows.

Impact on Prognosis and Treatment Selection

The new molecular classification of colorectal cancer has profound clinical implications. Its primary goal is to differentiate patients who would benefit from treatment from those who would not. Dr. Hans-Joachim Schmoll, MD, emphasizes this will revolutionize adjuvant chemotherapy decisions.

For example, a patient's sex, age, tumor location, and specific genetic features will combine to indicate a very distinct prognosis. This information will directly inform the need for a specific prophylactic chemotherapy regimen. Dr. Anton Titov, MD, explores how this moves beyond well-known mutations like KRAS, NRAS, BRAF, and microsatellite instability.

The Future of Personalized Colorectal Cancer Therapy

Personalized therapy means tailoring every aspect of care to the individual. Dr. Hans-Joachim Schmoll, MD, explains it requires knowing the specific biological features of the tumor and the patient. This precision approach will extend to decisions made after surgery.

It will also influence the kind of surgery a patient requires and how extensive that operation should be. Dr. Schmoll points to radiotherapy in rectal cancer as an area for change. Currently, all patients with locally advanced rectal cancer receive radiotherapy. These decisions must become more individualized based on the new molecular taxonomy.

Looking Beyond Known Genetic Mutations

The future of colon cancer treatment requires looking beyond a handful of genes. Dr. Hans-Joachim Schmoll, MD, states that expression profiling with 8, 10, or even 18 genes is not sufficient. Truly differentiating one colon cancer patient from another demands a more comprehensive analysis.

Dr. Schmoll is confident that further research will reveal more than three molecular stages of colon cancer. This will enable therapy based on the personally expected course of disease for each patient. Dr. Anton Titov, MD, concludes the discussion on this huge potential to improve outcomes through precision medicine.

Full Transcript

Precision medicine is here for colorectal cancer treatment. But current tumor classification is not optimal for selection of correct cancer treatment. Why is new molecular tumor classification important for all colon cancer patients? A leading colorectal cancer oncologist and research expert discusses colon cancer diagnosis and treatment options.

Personalized medicine, precision medicine for colorectal cancer treatment: advances in molecular genetics of cancer rewrite the old anatomic and histological classification of cancer. This is true for colorectal cancer.

Dr. Anton Titov, MD: You write in a scientific article: "It is becoming clear that colon cancer will be divided into five or six different subtypes. These subtypes will be based on distinct molecular characteristics of the tumor." "It can be predicted that description of this molecular taxonomy of colorectal cancer will have profound clinical implications."

What are the implications of the new molecular classification of colorectal cancer for colorectal cancer treatment?

Dr. Hans-Joachim Schmoll, MD: We look beyond the well-known mutations such as KRAS, NRAS, microsatellite instability or BRAF mutations in colon cancer tumors. First of all, we have the intention to divide colon cancer tumors into molecular categorized groups. Cancer characterization is done by third-generation sequencing technologies and by many molecular methods.

Dr. Anton Titov, MD: Distinct molecular subgroups of colon cancer can represent a specific prognosis for tumor patients. For the cancer classification taxonomy, patients with resectable colorectal cancers stages are used.

Dr. Hans-Joachim Schmoll, MD: The consortium of doctors decides on colon cancer classification. These are mostly patients with colon cancer at stage two and stage three. Only a minority of colon cancer patients used for classifying cancer are stage four colon cancer patients.

Dr. Anton Titov, MD: Let's look at stage two and stage three colorectal cancer patients. For now we have no real method to differentiate between these patients within the same stage of disease.

Dr. Hans-Joachim Schmoll, MD: We do not know how patients within stage 2 colon cancer differ in expected prognosis. We do not know the difference between the patients in response to chemotherapy. The same is true for stage 3 colon cancer.

The new taxonomy of colorectal cancer is the most important development. New taxonomy has to include many more patient groups than current classification includes. New colon cancer taxonomy should differentiate between patients who would benefit from treatment and who would not.

Dr. Anton Titov, MD: For these patients, adjuvant chemotherapy would make a difference? How do different patients respond to different chemotherapy medications?

Dr. Hans-Joachim Schmoll, MD: We have to investigate prognostic factors. We have to investigate response to treatment. Then we will have more precise colon cancer classification in the next three years.

But this new colon cancer classification would mean, for example, that we can say this: This patient of this sex who has this colon cancer tumor at that age, with this location of the tumor in the left part of the lower colon or in rectum or the beginning of the colon and so on, with these clinical signs and with these features in patient's genetic makeup—this patient may have a very distinct prognosis and needs a very distinct adjuvant prophylactic chemotherapy. This is the aim of this effort for new colon cancer classification.

We have to make colon cancer treatment more personal. It means really personalized treatment. Personalized therapy means we have to know the specific biological features of the tumor itself.

Dr. Anton Titov, MD: But it also means we have to know patient's biological characteristic as well. More personalized therapy also means precise decision on the kind of the treatment after the surgery, probably also about what kind of surgery a given patient has to have, how extensive the surgical operation has to be for this patient.

Dr. Hans-Joachim Schmoll, MD: Question of radiotherapy in rectal cancer: currently all patients with locally advanced rectal cancer get radiotherapy. These decisions must be more individualized.

Dr. Anton Titov, MD: It is a huge potential of this new taxonomy of colorectal cancer. Why do we need new taxonomy of colon cancer? It is clear that it is not just one or two or three molecular subtypes of tumor in one gene or one location, or one gene expression pattern even. Expression profiling with 8, 10, 15 or 18 genes is not enough to really make the difference from one colon cancer patient to the other. But I'm sure that further research will be done. It will be more than three stages of colon cancer.

Dr. Hans-Joachim Schmoll, MD: Colon cancer treatment will be more individualized.

Dr. Anton Titov, MD: Therapy will be based on the personally expected course of disease for each colon cancer patient.

Colorectal cancer staging: how new molecular classification helps to personalize cancer treatment. Gene expression classification of colon cancer is crucial in era of precision medicine. Molecular markers identify subtypes of colon cancer that can be treated separately. Patients can benefit from new genetic classification of colon cancer and rectal cancer.

Personalized medicine is here today. New colon cancer treatment methods have to be applied to correctly selected patients. We have to look beyond the well-known mutations such as KRAS, NRAS, microsatellite instability or BRAF mutations in colon cancer tumors.

Colon cancers at stage two and stage three are very different between each other at the same cancer stage. New colon cancer taxonomy should differentiate between patients who would benefit from treatment and who would not. Personalized therapy also means precise decision on the kind of the treatment after the surgery.

A leading colorectal cancer expert discusses new molecular classification of colorectal cancer.