Lu-PSMA Treatment - Today and Tomorrow

An exciting proof-of-concept study of Lutetium-177 PSMA (Lu PSMA) was published in the journal Lancet Oncology. Lu-PSMA has been described as “a disruptive therapy and has the potential to change practice” in the future treatment of men with end-stage prostate cancer.  

Lu-PSMA, a nuclear therapy, has been used in Germany for many years under compassionate use basis.  This particular study was conducted in Australia. The study results offer hope for men with end-stage prostate cancer who have exhausted all their treatment options.

Lu-PSMA seems to be a highly targeted form of nuclear medicine that has been shown to reduce pain, improve the quality of life and in some cases, significantly extend survival of men who have exhausted all other therapies.

According to the Australian researcher, Professor Michael Hofman, who led the study at the Peter MacCallum Cancer Centre in Melbourne, "In some men, the results are striking." 

There has been a small number of retrospective case reports published previously. However, this Australian study is the first formal assessment of the therapy.

Lu-PSMA therapy is a two-stage therapy. The first stage involves locating the cancer spread and then using a targeting molecule (PSMA-617) with a radioactive payload (Lutetium-177) that destroys the cancer cells.

In the above picture see the before and after scans of six men from the study. On the left, the cancer is shown in red before treatment. The right is afterward. 

The pharmaceutical company, Endocyte, which owns the rights to Lu-PSMA is now planning a trial in the US and Europe. There are also additional trials being scheduled in Australia. 

Lu-PSMA is not curative, however, given the very dramatic results this small study involving men who had exhausted all their treatment options we can feel hopeful that it might offer even more possibilities at an earlier stage of the disease.  

This reported Australian study involved 30 men for whom no further treatment was available.  The average survival of all the trial participants was 13 months that included those who died quickly as well as men who are still alive, more than two-and-a-half years after starting the study.

One of the endpoints of the study was to evaluate changes in the blood biomarker prostate specific membrane (PSA) which is assumed to reflect prostate cancer activity.  When PSA is reduced in men with advanced prostate disease, it indicates a reduction in cancer activity.

In the study, it was shown that PSA was halved in almost 60% of the subject men. In 20% the response was exceptional with their PSA falling by more than 80%. Whole body scans (see figure provided in this post) confirmed these dramatic changes.

 This investigational treatment does not seem to work for everyone.  In the study being cited at one extreme, one man had no reduction in his PSA while another man's PSA became undetectable and 18 months later he still has no symptoms and clear scans.

Generally, most men who responded to the treatment report feeling feel better quite quickly. Overall, there was a 37% reduction in pain with scans showing tumors shrinking in 82% of the subject men.

"Some men reported the therapy gave them rapid relief from otherwise severe bone pain and that they had more energy for daily tasks and to enjoy family time," said Hofman.

During the first stage of treatment (identifying the cancer location) men have a PSMA-PET scan to identify and locate their cancer.  This scan uses gallium-68 or flourine-18 that are attracted to and bind strongly to the cancer cells.  These scans do not have any killing power but radiate out of the body where they can be detected by the PET scanner.

These scans create a three-dimensional whole-body picture that can detect prostate cancer clusters as small as a few millimeters in size, which is far more sensitive than CT or MRI.

For the second "seek and destroy" stage, lutetium-177 is labeled to PSMA and injected.

Like tiny, heat-seeking missiles, these molecules look for cells with a high expression of PSMA. They attach to them and become absorbed. Once inside, they unload their radiation. 

According to Hofman, this investigational therapy is exquisitely targeted. Unlike chemotherapy that affects many other parts of the body, it delivers its toxic load directly into prostate cancer cells.

Unlike external beam radiation, which may radiate a large area damaging adjoining tissues and organs, lutetium enters the cells directly with its high energy "killing" particles only capable of traveling one millimeter, thereby limiting damage to normal tissue.

Lu-PSMA therapy’s main side effects are a dry mouth and eyes, but these are usually mild and recover over time.  A man having the therapy will need to be kept in isolation for a period due to the radiation. 

We need to remember that there is still significant additional research needed to establish Lu-PSMA’s efficacy.  However, for anyone who has exhausted all their therapy alternatives, before beginning of any new clinical trials, you can consider taking a trip to Germany for compassionate treatment.   

For men living in Australia, there is a nationwide trial of 200 men approaching the final stages of prostate cancer.

It is comparing lutetium therapy Lu-PSMA with chemotherapy.  This trial, the TheraP trial,recently started recruiting and men can get information about it from their oncologist, urologist or from this link:

Cancer ABCs understands that there are other additional trials for men with earlier stages of prostate cancer being planned in Australia.  We applaud these important steps forward. 

This Treatment is a Potential Game Changer.

Joel T. Nowak, MA, MSW wrote this Post.  Joel is the CEO/Executive Director of Cancer ABCs.  He is a Cancer Thriver diagnosed with five primary cancers - Thyroid, Metastatic Prostate, Renal, Melanoma, and the rare cancer Appendiceal cancer.