Thank you to all 2020 Below the Belt Research Fund applicants. ANZUP received a large number of high quality applications, and after careful consideration the research grants were announced at the 2020 Mini ASM.
The review panel selected the following successful applicants - congratulations to all.
Louise Emmett and Michael Hofman
PRIMARY 2: A prospective, multicentre, randomised study of Ga-68 PSMA /CT + mpMRI vs mpMRI alone for prostate cancer diagnosis.
MRI is now routinely utilised for the diagnosis of prostate cancer in Australia. However, it still misses about 15-20% of important cancers, and about half of the biopsies undertaken after MRI are negative, because MRI is not completely accurate. PSMA PET is a new technique that is helpful in staging men who have already been diagnosed with prostate cancer. The PRIMARY trial - currently underway - is assessing the value of PSMA PET in men who are suspected of having prostate cancer, and are undergoing both an MRI and a prostate biopsy.
This trial proposes to randomise men between MRI + biopsy (if required) - the current standard of care in Australia, and MRI /PSMA + biopsy (if required). The study hypothesis is that PSMA MRI will both reduce unnecessary biopsies and improve accuracy of prostate cancer diagnosis, compared to using MRI alone. Also, a health economics analysis to assess cost to the community and QOL for men with prostate cancer is an important component of this trial.
To date, the study has enrolled 230/309 men, and the results are looking promising for combination of PSMA and MRI to be more accurate than MRI alone in diagnosing important prostate cancers. There is the potential for imaging to play a much bigger role in diagnosis of prostate cancer and for the number of biopsies required to be safely reduced.
De-Intensification of Post ProstatEctomy Radiotherapy (DIPPER) incorporating clinical and imaging-based risk stratification: Part 1 – Pilot study (additional site)
This clinical trial will use modern PET scanning (PSMA PET/CT) in men who have a rising PSA level after prostate surgery to select those who can potentially avoid or minimise additional (radiation, hormone) treatments safely. Previous studies reported that these men who have a negative or confined PSMA PET have good treatment responses to limited radiation treatment without hormones compared to men whose cancer has spread. Some men with a negative PSMA PET who were not treated did not progress over 3 years, suggesting that some men can be spared treatment altogether.
The purpose of this trial is to determine if some men with low risk cancer who can be safely monitored, then avoid treatment side effects without compromising disease control.
This trial will be limited to men who are deemed as “Low Risk” for spreading cancer using criteria from the European prostate cancer guidelines. If the PSMA PET result is negative, the trial will randomly choose close surveillance and delayed treatment or standard radiation treatment. If the PSMA PET result is positive and confined, men will receive standard radiation treatment to the prostate and the other half will receive additional hormone treatment. If positive and spread outside the prostate area, selected treatments and responses will be monitored for some years.
PRIUS MR: Prostate Re-Irradiation Using SABR and MRI Guidance
This study aims to demonstrate the feasibility of using the next generation of radiotherapy machine with an onboard MRI scanner (known as an MR-linac, or MRL) to give further radiation to the prostate in men who have previously received prostate radiation and now have a recurrence in the prostate gland. The efficacy and tolerability of this approach has been demonstrated in a number of small series using a conventional radiation machine, but the dose and method of delivery have varied significantly and thus the results are difficult to generalise or apply clinically.
Controlling the recurrent cancer this way can spare men the toxicity of hormone therapy which, while usually effective, carries a raft of side effects that can significantly impact quality of life. The potential exists for re-irradiation to be delivered to a higher dose and with less risk of toxicity by harnessing the unique potential of the MRL to deliver treatment more accurately.
If this treatment is feasible on the MRL, the intention is to broaden this to a national study to explore in more detail the optimal dose for this treatment.
MEMENTO: Biomarker discovery in metastatic hormone sensitive prostate cancer (MEtastatic Prostate Cancer MEthylation and Transcriptional biOmarker Study)
In recent years, we have learned that changes in prostate cancer genes can influence the risk of developing metastatic prostate cancer. This study aims to improve our understanding of how genes are controlled in metastatic prostate cancer, and specifically how gene control might determine how men respond to standard treatments (such as hormone therapy and chemotherapy).
By way of examining cancer biopsies taken at the diagnosis of metastatic prostate cancer, we will test for an important genomic feature called DNA methylation – a process involved in ‘silencing’ genes. We believe DNA methylation will provide important information about why some cancers are more aggressive than others and why men may respond to treatments differently. We will use DNA methylation information from the tumours and compare it to information of how men diagnosed with metastatic prostate cancer responded to standard treatments. We then hope to use this as a strong foundation to design larger studies to test DNA methylation in prostate cancer clinical trials, to prove that it is an important test in the clinic to identify the risk of aggressive disease and to tailor the optimal treatment choice for patients. Ultimately, this study aims to build on our scientific knowledge of prostate cancer in order to improve ‘precision care’ of men with metastatic prostate cancer.
68Ga-PSMA PET as a potential Imaging biomarker post tyrosine kinase inhibition of metastatic clear cell Renal cell Cancer (PIRC) – a pilot study
Immunotherapy and tyrosine kinase inhibitors (tablet targeted therapies) have revolutionised the treatment of advanced clear cell renal cell cancer (ccRCC), the most common type of kidney cancer. Computed tomography (CT) scans are used to determine where the cancer is and how it is responding to treatments. CT scans have limitations, however, only showing us tumour deposits physically and not reflecting how active they are.
A new type of positron emission tomography (PET) scan, targeting “prostate specific membrane antigen” (PSMA), appears very useful in diagnosing the extent of ccRCC spread before treatment and to see if the treatment is working. This is likely because RCC deposits have many small blood vessels, with the PSMA protein being found in these blood vessels, and not because it is related to the prostate.
Many tablet targeted therapies affect cancer blood vessel development, and as such, this project seeks to understand whether a PSMA PET scan is useful in visualising patients’ tumours after they have been treated with these therapies.
Additionally, we want to understand if tumours that remain active on PSMA PET might be sensitive to another tablet targeted therapy, potentially allowing us to tailor the right treatment, to the right patient, at the right time.