New, experimental, radioactive lutetium and actinium treatments may significantly aid the treatment of advanced prostate cancer

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Treating advanced prostate cancer is a challenge as the treatments often have side effects and the cancer tends to recur despite treatment. Recent treatment experiences show that combining new, experimental 177-lutetium-PSMA- and 225-actinium-PSMA radioisotope treatments with the traditional treatment procedure may provide quite substantial additional treatment to incurably metastatic prostate cancer alongside hormonal treatments and chemotherapy.

Prostate cancer is the most common type of cancer globally. The risk of developing the disease increases with age. Prostate cancer commonly spreads to the bones and lymph nodes. Advanced prostate cancer is usually an incurable disease that requires treatment throughout the person’s life. The first-line treatment for metastatic prostate cancer usually includes pharmacotherapy, most commonly consisting of hormonal therapy and chemotherapy, in other words cytostatic treatment. Radiotherapy can be included in the treatment with special techniques, even if there are extensive metastases. Local radiotherapy for a prostate combined with pharmacotherapy has also proved to be an effective treatment for advanced prostate cancer. Hormonal treatments and chemotherapy can remain effective for long periods but usually lose their efficacy over time. In these situations, the second-line treatment of radionuclide therapy with a radioactive substance (radium or samarium) that targets the bones has been found to be both an effective and safe treatment option when metastases exist only in bone structures.

New radioactive drugs destroy aggressive and metastatic cancer cells

In addition to radium and samarium, new radioactive drugs, experimental 177-lutetium-PSMA- and 225-actinium-PSMA*, have now been discovered. Docrates Cancer Center was the first in the Nordic countries to launch the new 177-lutetium-PSMA treatment under special permission in early 2017 for the treatment of patients whose hormonal and other basic treatments designed to prevent recurrence are no longer effective. So far, Docrates has administered 177-lutetium-PSMA treatments to about 100 men. Thousands of men have been treated around the world as the treatment has been available in or outside clinical trials in five countries around the world in addition to Finland.

In Finland, 177-lutetium-PSMA treatments have also been provided at the Helsinki University Hospital as experimental treatment outside clinical trials.

177-lutetium-PSMA- and 225-actinium-PSMA treatments are based on the PSMA molecule that occurs in abundance on the surface of aggressive and metastatic cancer cells. The 177-lutetium-PSMA and 225-actinium-PSMA drugs reach the surface of these active cancer cells directly, guided by the carrier drug and regardless of their location, and locally destroy them using radioactive radiation. The 177-lutetium-PSMA- and 225-actinium-PSMA treatments require an examination using tracer imaging to confirm the PSMA positivity of the cancer cells.

Based on the monitoring of treatment provided at Docrates, the new 177-lutetium-PSMA- and 225-actinium-PSMA treatments have proven to be quick and effective in removing metastases of prostate cancer from the prostate, lymph nodes, bones, lungs and liver. In addition, the treatment has proved suitable even for patients who have not been able to use other means of treatment due to considerable side effects or whose disease keeps advancing or recurring despite treatment.

Promising results in clinical studies

The international randomised controlled trials are also in their third phase, after which official and more detailed Current Care Guidelines can probably be issued for the cancer cases selected for treatment. However, promising results  have already been presented in ESMO2018 and ESMO 2021.

October’s ESMO2018 conference, according to which the dose escalation study had shown that even a dose three times larger than that proved effective at Docrates was found safe and well tolerated without the appearance of the toxicity that restricts the dosage.

The VISION study results** were presented in ESMO2021 conference: the results showed that treatment with 177-lutetium-PSMA significantly improved overall survival (OS) in patients with PSMA-positive metastatic castration-resistant prostate cancer.

According to the recent, preliminary treatment experiences, the 177-lutetium-PSMA- and 225-actinium-PSMA treatments have considerable effects on the decrease of the PSA value measuring prostate cancer and even the complete disappearance of aggressive staging in imaging; in the process, part of the patients’ PSA values dropped by up to 90% and the imaging indicated that at least the visible parts of aggressive staging had disappeared. In addition, the treatments also seemed to increase the survival time and non-recurrence after the treatments more than what had previously been achieved with patients using chemotherapy in line with Current Care Guidelines. The patients had been administered an average of 3 (1–8) treatments.

New option requiring studies as first-line treatment for prostate cancer

According to Professor Jukka Kemppainen and Professor Timo Joensuu from Docrates Cancer Center, any means necessary should be adopted when treating an aggressive prostate cancer to maintain a good quality of life despite the disease and potentially increase the patient’s expected lifespan. The 177-lutetium-PSMA- and 225-actinium-PSMA treatments may prove an excellent additional option, particularly for elderly patients who may find the traditional chemotherapy challenging and even contraindicative due to severe side effects. The most common known side effect of the 177-lutetium-PSMA- and 225-actinium-PSMA-radioisotope treatments is drying of the mouth which is alleviated by cooling down the salivary glands during treatment. Long-term side effects must still be studied, and more randomised research is required.

– According to recent experiences, the 177-lutetium-PSMA- and 225-actinium-PSMA treatments should be studied as new potential treatments for incurable, metastatic prostate cancer instead of and alongside chemotherapy, and not only as second-line treatment but also as first-line treatment, says Timo Joensuu.

*177-lutetium-PSMA- and 225-actinium-PSMA have a special permission for compassionate use by the Finnish Medicines Agency (Fimea).

References:

Kairemo, K. & Joensuu, T. (2018). Lu-177-PSMA treatment for metastatic prostate cancer: case examples of major responses, Clinical and Translational Imaging, 6, 223-237. https://link.springer.com/article/10.1007/s40336-018-0274-y

ESMO 2018 Congress. Local radiotherapy improves survival in metastatic prostate cancer with low disease burden [ESMO 2018 Press Release]. https://www.esmo.org/Press-Office/Press-Releases/STAMPEDE-prostate-cancer-radiotherapy-Parker

Radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE): a randomised controlled phase 3 trial. Christopher C Parker, MD. Prof Nicholas D James, PhD. Christopher D Brawley, MSc. Prof Noel W Clarke, ChM. Alex P Hoyle, MRCS. Adnan Ali, MBBS et al. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)32486-3/fulltext

Multimodal Primary Treatment of Metastatic Prostate Cancer with Androgen Deprivation and Radiation. ANTICANCER RESEARCH 36: 6439-6448 (2016). Timo Joensuu et al. http://ar.iiarjournals.org/content/36/12/6439.full.pdf+html

Lutetium-177–PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. Sartor, Morris & Krause. NEJM.org (2021).

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