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Theranostics for prostate cancer

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Managing a disease such as prostate cancer often requires continual tests and treatments. Both tests and therapies can have side effects. They are also expensive and interrupt daily life. A new approach to managing diseases such as cancer combines both therapy and diagnostics. It's called theranostics: a combination of the two words. The diagnostic side helps to monitor the individual progress of the patient on each day that the therapy is administered. Theranostics aim to increase survival, whilst reducing the overall amount of tests and treatments that a patient must undergo.

Although theranostics is considered a new approach, it's a concept that is well-known to those in the nuclear medicine field. It started with the use of radioactive iodine to both diagnose and treat patients with thyroid cancer in the 1940s. In the past few years, interest in developing theranostics for cancers has greatly increased.

A new theranostic for prostate cancer has been recently reported in the media. Lu177-PSMA-PET combines the diagnostic PSMA-PET/CT scan with a radioactive compound that aims to kill prostate cancer cells. The PSMA scan shows where the cancer has spread to. It lights up the PSMA protein which is found in prostate cells, with increased amounts found in prostate cancer cells. As a diagnostic, a radioactive "tracer" detects the PSMA. The radioactive component is an element called lutetium 177 (Lu177). It has a half-life of 6.7 days and emits radiation that can penetrate an 2mm into human tissue. Therefore as a therapy, it can kill cells within approximately 2mm of where the PSMA is detected.

This theranostic allows doctors to see where the cancer has spread to and target it based on that very same test. By using PSMA-PET, this theranostic approach uses what is currently the most advanced diagnostic test for prostate cancer in Australia. Each treatment derives an image to show both where the tumours appeared at that time and where the treatment was targeted.

Melbourne was recently host to the 2016 Theranostics Conference. A number of small but promising studies examining the safety and effectiveness of Lu177-PSMA-PET were presented. This theranostic was used for men with metastatic castration-resistant prostate cancer (mCRPC). Although it's early days, the initial clinical data tell us the treatment is safe and that large clinical trials are warranted.

A/Prof Alexander Haug presented data from a small trial of Lu177-PSMA-PET at the Medical University of Vienna in Austria. His team used a treatment approach considered "aggressive". Fifteen patients with mCRPC were treated with 3 cycles of 177Lu-PSMA-PET every 4 weeks. Their response to treatment was tested using PSMA PET/MRI during the treatments and up to four weeks after the last cycle.

Out of the 15 patients, 12 were able to complete all the cycles. A decrease in PSA levels was seen in 11 out of the 15 patients. Five of the patients had a partial response to the treatment and the disease in four of the men stabilised. The cancer progressed in only three of the men. Fortunately there were very few side effects to the treatment, all of which were mild. A/Prof Haug concluded that the theranostic was safe and made an effective treatment in these men. Although this was a short trial with only 15 patients and no control group, the good results indicate that larger, more clinical trials are feasible and warranted.

More good news came from Dr Madhav Yadav from Delhi in India. Dr Yadav described the treatment of 31 patients with mCRPC with Lu177-PSMA-PET. Based on PSA levels, 22 of the patients had a complete or partial response. Three men had stabilised disease and only 6 of the 31 men suffered disease progression by 3 months.  

A/Prof Michael Hofman of the Peter MacCallum Cancer Centre in Melbourne presented initial results from his trial assessing the safety of Lu177-PSMA-PET. Eight men with prostate cancer that were scheduled to undergo prostatectomy were treated with Lu177-PSMA-PET. All patients tolerated the treatment well, with no bad side effects. Currently the Petermac is running a trial for patients with mCRPC that has progressed despite hormone therapy and chemotherapy. This trial will now assess how effective the treatment is. It's a small-scale, short term trial but the data will hopefully lead to a large clinical trial necessary to show the theranostic is effective and define the best treatment pathways. Hopefully good results in large, multicentre trials will lead to the Lu177-PSMA-PET becoming part of conventional treatment for mCRPC.

Availability of the Melbourne Lu177-PSMA-PET trial

The small trial at the Peter MacCallum Cancer Centre is recruiting patients who have prostate adenocarcinoma, with metastatic castration-resistant prostate cancer. Eligible patients are those whose cancer has progressed despite treatment with chemotherapy and Abiraterone or Enzalutamide. See the trial description for more details. Currently there are few positions left. However an application has been made to extend this trial to more patients, which will hopefully occur soon.

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