Teragnosis: a new hope against cancer

The doctor José Luis Carreras is excited when he talks about teragnosis, a powerful strategy that works like a precision missile against the cells of some types of cancer. Carreras, head of Nuclear Medicine at the San Carlos Clinical Hospital, in Madrid, speaks of "spectacular results" in certain terminal patients. The doctor recalls the case of a 62-year-old German man with prostate cancer and a massive spread with bone metastases. After an experimental treatment with teragnosis at the Central Clinic in Bad Berka (Germany), eight months later he appeared clean. He went back to work and to play sports. And three and a half years later, he was still cancer-free, Carreras explained in February in a scientific session at the Royal National Academy of Medicine in Madrid.

Teragnosis has been one of the protagonists of the largest annual congress dedicated to cancer in the world, that of the American Society of Clinical Oncology (ASCO), held until this Tuesday on the internet. The term teragnosis is a combination of two words: therapy and diagnosis. With the same molecule, the disease can be diagnosed and treated. The strategy, used for decades against thyroid cancer, is now being used with promising results in other tumors, such as neuroendocrine tumors and, above all, prostate cancer, the most common in men.

Dr. Michael Morris of Memorial Sloan Kettering Cancer Center in New York presented the latest results of advanced prostate cancer teragnosis at the ASCO conference. The technique consists of using a molecule with high affinity for PSMA, which is a protein that is usually found in large quantities in prostate cancer cells. To make the diagnosis, this PSMA-related molecule binds to a radioactive chemical element, gallium-68, which glows on a positron emission tomography (PET) scan. For treatment, the same molecule binds to another chemical element, lutetium-177, which emits local radiation that kills cancer cells. It is like shooting first an arrow with a light bulb and then another arrow with a small explosive charge.

“This is not killing flies with cannon shots, like other techniques.

It means going directly to the tumor cell and destroying it in situ ”, applauds the doctor José Luis Carreras

The Morris trial involved 831 patients with metastasis and castration-resistant prostate cancer, a type of tumor that is usually fatal.

Patients who received treatment with teragnosis lived for 15.3 months, compared to 11.3 months for men who received standard therapy.

Four months apart - 35% more - may seem like a small thing, but these were practically hopeless patients, in whom chemotherapy and hormonal treatments had already failed.

The doctor José Luis Carreras emphasizes that the four extra months of survival are an average. "There are cases that do not respond, but there are some in which the improvement is spectacular," he says. His team at Hospital Clínico San Carlos will participate in two clinical trials of teragnosis against advanced prostate cancer starting in September. “This is not the future, it is the present. It is precision and personalized molecular radiation therapy. It is not killing flies with cannon shots, like other techniques. It means going directly to the tumor cell, putting radiation into it and destroying it

in situ

without affecting the surrounding healthy tissues ”, he celebrates.

Carreras believes that in the next few years there will be molecules "for all types of tumors", such as the Fibroblast Activation Protein Inhibitor (FAPI), related to the cells of various malignant neoplasms. “Almost all tumors have fibroblasts [a type of cell abundant in fibrous tissues] mixed with tumor cells. With FAPI you can send the radiation to the fibroblasts, but since the radiation range from lutetium-177 is one or two millimeters, you also kill the tumor cells. The advantage of the FAPI is that it is valid for any type of tumor ”, Carreras points out. The doctor clarifies that there is still little evidence of the therapeutic efficacy of this strategy, in part due to the low radiation dose achieved in tumor cells.

"Teragnosis is a very beautiful concept and it comes very strong for the treatment of prostate cancer", says the oncologist Teresa Alonso

The promising experimental treatment presented at the ASCO conference, named 177Lu-PSMA-617, was in development at the US biopharmaceutical company Endocyte.

The Swiss pharmaceutical giant Novartis announced in October 2018 the purchase of this company for about 1.7 billion euros.

Some previous research, such as a study with 30 patients in 2016 at the University Hospital of Heidelberg (Germany), had already shown the potential of this strategy.

The oncologist Teresa Alonso, from the Ramón y Cajal hospital in Madrid, believes that the profit margin of this therapy "will surely be much higher" if it is administered to patients earlier. "The concept is old, but now it is going to become quite fashionable," says Alonso, also scientific secretary of the Spanish Society of Medical Oncology (SEOM). The researcher recalls that it is a strategy similar to the one that has been used for decades against thyroid cancer, in this case with iodine-123 for diagnosis and iodine-131 for treatment. And, in recent years, the technique has also been adopted against neuroendocrine tumors, with an annual incidence of less than 10 cases per 100,000 inhabitants. "Teragnosis is a very beautiful concept and it comes very strong for the treatment of prostate cancer", applauds the oncologist.The researcher, however, keeps her feet on the ground: "This is not the cure for prostate cancer, obviously."

The president of the ASCO congress, the American oncologist Lori Pierce, has celebrated the results of teragnosis against advanced prostate cancer. "The success of this treatment shows the importance of investigating alternatives to traditional cancer therapies," Pierce said in a statement. Michael Morris, head of the prostate cancer department at Sloan Kettering, has directly suggested that authorities study the possibility of making 177Lu-PSMA-617 a new standard treatment for these patients.

Doctor José Luis Carreras regrets the "slowness" of drug regulatory agencies when approving new therapies.

One of the problems is its high price.

Carreras estimates that a treatment with teragnosis of a neuroendocrine tumor costs about 65,000 euros per patient.

“It achieves a longer survival than the other alternatives and the price is competitive.

It is not more expensive than the chemotherapy it replaces ”, he argues.

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