Cancer refers to the appearance, proliferation and invasion of malignant cells into surrounding normal tissue, and oftentimes to other distant sites of the body. They are characterized by their ability to grow without entering the usual cell death phase, so that they are capable of  unregulated cell division and growth.

What is refractory cancer?

The meaning of refractory cancer is cancer that fails to respond to medical treatment. This may present as resistance to treatment from the start, or the acquisition of resistance by the cancer cells during the course of therapy.

Refractory cancer is also called resistant cancer. Clinically, refractory cancer is identified if the disease fails to respond or responds initially but then becomes worse within a short time period. The signs or symptoms of the disease worsen after a short duration in which there may or may not be improvement.

Refractory cancer is different from relapsed cancer, which refers to the return of cancer after it initially shows signs of improvement.

Refractory cancer could bear different meanings depending on the situation, of course. In certain clinical trials, for instance, a patient may be accepted for treatment only if both first-line and second-line treatment have failed.

Sometimes, a refractory cancer may be one which does not respond to a specific treatment. Hormone-refractory prostate cancer, for instance, may respond at first to castration or androgen deprivation therapy, for a time, but then develops resistance to the treatment.

What specific problems does refractory cancer cause?

Refractory cancer can cause obstruction of various hollow organs, or interfere with their function. It can also cause intractable pain, often requiring opioid analgesia.

Other issues include:

• Bone marrow suppression
• Lymphatic obstruction leading to swelling of various parts of the body
• Bone pain and pathological fractures, and spinal cord compression
• Neurological syndromes due to nerve involvement
• Psychological problems
• Severely reduced quality of life

Managing refractory cancer

Refractory cancer is typically treated by second-line or third-line treatment, usually with a combination of more harsh drugs, or by enrollment in a clinical trial in which novel drugs are used. Newer technologies are evolving to help manage this difficult situation.

Molecular profiling of tumors

A recent technique which is being used to study better treatment avenues for different cancers is molecular profiling. A molecular profile of the tumor is obtained to provide targeted therapy which is individualized for each person. The result is a longer duration of survival without disease progression (progression-free survival, PFS) than achieved with the latest round of conventional treatment.

Since refractory disease may be due to individual differences in pathophysiology, the use of tumor and other biomarkers will help predict or diagnose the occurrence of the tumor, its prognosis and response much earlier than could be expected otherwise. The outcome will be the ability to treat patients with targeted therapies rather than the wholesale application of standard systemic treatments with their severe toxicity.

The use of prognostic biomarkers allows measurement of the changes in the germline, epigenetic alterations, and other markers like miRNA that regulate the cell cycle, or circulating tumor cells. This tells researchers about the risk of invasion and metastasis.

Imaging tools

The use of CT and PET scanning is also intended to improve early detection of refractory cancer and its management.

Molecular diagnostics

The use of specific molecules to identify certain genes, detect gene expression, and look for translated proteins and metabolites is molecular diagnostics. This growing field can help make novel bundled cancer therapies available. These provide more efficient and cost-effective as well as personalized treatments for cancer.

Research into the treatment of refractory cancers is still in its early stages. Attention is being paid to various miRNAs which act specifically on the cell cycle responsible for cell proliferation, and the way various tumor cell lines respond to these molecules. It may be possible to deliver these miRNAs to the tumor to suppress its growth.

Several countries are encouraging larger programs which will make advanced newer experimental therapies available to more patients with their consent, provided the physician is supplied with enough scientific or experiential information to support this choice. Expanding the scope of such research applications is the only way to find out if the novel technology works, is safe, and is useful in multiple types of tumors.

Once all medical treatment fails to control tumor growth or spread, curative treatment is replaced by palliative care. This is offered to deal with the practical problems facing the patient, such as pain, obstruction of various organs, or general wasting.

Further Reading

• All Refractory Cancer Content

Written by

Dr. Liji Thomas

Dr. Liji Thomas is an OB-GYN, who graduated from the Government Medical College, University of Calicut, Kerala, in 2001. Liji practiced as a full-time consultant in obstetrics/gynecology in a private hospital for a few years following her graduation. She has counseled hundreds of patients facing issues from pregnancy-related problems and infertility, and has been in charge of over 2,000 deliveries, striving always to achieve a normal delivery rather than operative.