Top 10 prostate cancer research stories from 2018

[Wendy_Winnall]

Our first blog this year describes the top 10 prostate cancer research stories of 2018, as judged by PCFA staff:

Darolutamide for men with non-metastatic castration resistant prostate cancer

Darolutamide is a new drug being developed to treat prostate cancer. Current trials are testing its success in treating men with advanced prostate cancer whose PSA is rising, despite hormone therapy (androgen deprivation therapy: ADT). These patients do not yet have scans showing tumours, and are referred to as having non-metastatic castration-resistant prostate cancer.

Darolutamide is being jointly developed by Finnish company Orion and German company Bayer. These companies have recently announced good news from their phase 3 ARAMIS trial. The ARAMIS trial is testing the success and safety of Darolutamide for patients with non-metastatic castration resistant prostate cancer who are currently being treated with ADT. Over 1500 patients have joined the trial. They were randomly assigned to take Darolutamide or a placebo with their ADT medication. In October 2018, the companies announced that the trial had met its primary endpoint. Darolutamide significantly extended the length of time before evidence arose of cancer spreading, compared to placebo.

A US patent for Abiraterone (Zytiga) has been ruled invalid

A key US patent for the use of Abiraterone (Zytiga) for treating metastatic prostate cancer has been ruled invalid by a US court. Once a drug comes off patent, it can be made and sold as an identical chemical, called a generic, by other companies. The invalid ruling could therefore lead to cheaper versions of Abiraterone becoming available in the US. An appeal has been filed by Johnson & Johnson, the owners of the Abiraterone patent. The verdict is expected in January, 2019.

Abiraterone is covered by an Australian patent expiring on 23rd Aug 2027. It’s subsidised by the PBS for use by Australian men with metastatic prostate cancer. Therefore, its cost to patients is reasonably low, at a maximum of $39.50 per 120 tablets of 250mg. However, the cost to the Australian government for subsidising the drug is much higher, at $3604.58 for the same packs. If the Australian patent is also overturned, this would mean a considerable saving for the PBS budget, allowing other drugs to be subsidised. 

These issues were described in a recent research blog.

SBRT/SABR benefits men with oligometastatic prostate cancer

After radiotherapy or surgery, prostate cancer sometimes returns as a few small tumours that have spread. This is referred to as oligometastatic prostate cancer. Two recently published clinical trials have indicated that a radiation-based treatment can benefit men at this early stage of metastatic prostate cancer. The treatment is called stereotactic body radiotherapy (SBRT). It’s also known as stereotactic ablative body radiotherapy (SABR).

The STOMP trial tested SBRT/SABR for men who had not yet started ADT. This trial asked whether the treatment could delay the need for ADT. The STOMP trial showed that men receiving metastasis-directed therapy took longer to need ADT. It took an average 21 months before the men receiving radiation needed ADT, compared to 13 months for the men who had surveillance only. The treatment was considered relatively safe. Some of the side effects from the treatment were “looser stools” in one patient and temporary muscle soreness in another.

The Australian POPSTAR trial asked whether SBRT/SABR was a safe and feasible treatment for men with oligometastatic prostate cancer, regardless of previous ADT. Over 1/3 of the patients having treatment in this trial had no cancer progression and no need for ADT over the 2-year trial period. 93% of the men in the study did not see these small tumours grow in the 2-year time-period. Longer-term follow-up will be needed to ask how long this treatment can hold back the tumours.

PCFA is proud to have supported the POPSTAR clinical trial, through funding from The Movember Foundation.

These trials were described in a recent research blog.

Secretion of IL-23 protein drives prostate cancer towards hormone therapy resistance.

Swiss scientists gained a better understanding of what happens to cells when prostate cancer becomes resistant to hormone therapy (androgen deprivation therapy: ADT). Their laboratory experiments showed that myeloid cells produce and secrete a protein called IL-23. IL-23 can take-over the role of testosterone when testosterone is blocked by ADT. When testosterone and similar hormones are blocked, IL-23 can promote the growth of prostate cancer through the same molecular pathways that testosterone would have used. The researchers used mice to show that a drug blocking IL-23 can restore the effectiveness of ADT, stopping tumour growth. The scientists propose that drugs blocking IL-23 can prevent resistance to ADT and therefore would be useful to combine with standard therapies. Their results were published in Nature, one of the world’s top journals.

Comparing open to robotic-assisted prostate surgery: 2-year outcomes.

This landmark Australian trial is the first to directly compare the two types of surgery for removing a prostate: open surgery (radical prostatectomy) and robotic-assisted prostatectomy. The randomised controlled trial followed 157 Queensland patients with localised prostate cancer who had robotic-assisted surgery and 151 who had open surgery. Two years after surgery was performed, the success and side effects were compared across the two groups of patients. The researchers were surprised to find a slightly higher proportion of men had rising PSA levels by 2 years after open surgery. This happened despite a lower proportion of these men having a positive surgical margin, indicating some cancer left behind. The researchers doubt that this slight difference in PSA levels is real, as the numbers of men with new tumours on scans were the same in both groups.

The study also showed no significant differences in urinary function, sexual function or psychological distress, measured by surveys during the 2 years after treatment. The robotic-assisted surgery resulted in shorter hospital stays, less pain during recovery and lower blood loss. It also resulted in less use of tablets and sexual aids, even though erection firmness was considered similar.

Overall, there were very few differences between the outcomes for open surgery and robotic-assisted surgery in Australia. This study was described in a recent research blog.

Olaparib and Abiraterone work well together

Olaparib (Lynparza) is a breast and ovarian cancer drug that is being trialled for prostate cancer patients. Previous trials have shown that men with metastatic castration resistant prostate cancer (mCRPC) benefit from Olaparib if they have mutations in DNA repair genes. Exciting new results from a 2018 trial showed that Olaparib can benefit men without these gene mutations, if the drug is combined with Abiraterone (Zytiga). This international trial compared outcomes for men with mCRPC who took Abiraterone and Olaparib, to men who took Abiraterone and a placebo. Men who took Abiraterone and Olaparib went an average of 13.8 months before their cancer progressed (or they died). This was significantly longer than the men who only took Abiraterone, whose cancer progressed after an average of 8.2 months. The drug combination worked for many men with mCRPC, despite their lack of DNA repair gene mutations. Nausea, constipation and back pain were common side effects.

This trial was described in a research blog from June 2018.

New PSA testing guidelines for the United States

In 2018 the US Preventative Services Task Force (USPSTF) revised their recommendations regarding PSA testing for prostate cancer in the US. They have stated a C rating for PSA screening, recommending “offering or providing the service to individual patients based on professional judgment and patient preferences”.

Previously, the USPSTF had down-graded their screening advice to “D” in 2012. This meant that PSA screening of men without symptoms was discouraged. The D rating was established after a review of evidence by experts that indicated no benefit of screening above the risks. Since then, results from two large randomised controlled trials and other studies have led to a rethink of this recommendation. The new rating should see PSA testing rates increase in the US, hopefully saving lives of US men from this disease.

Meanwhile, in Australia, PSA testing guidelines were released by PCFA and Cancer Council Australia in 2016. These guidelines aim to maximise the benefits and minimise the harms from PSA tests, by recommending testing for those who would benefit, and who have made an informed choice to be tested. This research blog from May presents a comprehensive description of PSA testing guidelines and their effects in the US and in Australia.

PCFA is proud to be a world-leader in establishing evidence-based PSA testing guidelines that recommend testing to those who will benefit, whilst aiming to minimise the harms of overdiagnosis.

Radiotherapy for men diagnosed with metastatic prostate cancer

Men who are diagnosed with prostate cancer that has already spread are usually treated with hormone therapy and chemotherapy. A new study has demonstrated that treating the prostate tumour with radiotherapy can improve survival times, but only for men whose tumours have not spread too far. During this study, men with prostate cancer that was metastatic at the time of diagnosis were randomly allocated to the control group (usual treatment) or usual treatment plus radiotherapy to the prostate. The men were classified as having either low or high disease spread. High disease spread was defined as having 4 or more bone tumours and one or more outside the spine or pelvis, and/or they had metastatic tumours in other regions than their bones. The results showed that men with low disease spread had significantly better survival rates if they had radiotherapy added to their usual treatment. 81% of men with low disease spread survived at least 3 years if they had radiotherapy, compared to 73% of men with low spread who didn’t have radiotherapy. This benefit of radiotherapy was not seen for men who had a higher disease spread.

This study has been described in a recent research blog. This useful short video from the researchers is a good summary of the study.

Discovery of a subtype of prostate cancer that may be susceptible to immunotherapy

A group of scientists from the US have made important progress in characterising metastatic prostate tumours. They discovered that some prostate tumours have lost a gene called CDK12. CDK12 regulates the production of proteins involved in repairing DNA. So loss of CDK12 in these cancers can lead to further problems, by increasing damage to DNA. Approximately 7% of men with metastatic castration resistant prostate cancer had this type of cancer. The researchers performed genomic analysis of 360 metastatic tumours, meaning that they sequenced all the genes used by these tumour cells. This analysis showed that the tumours with loss of CDK12 had many features in common. They were quite different to other types of prostate tumours with DNA repair problems, such as tumours with the BRCA2 gene mutation. The results indicated that tumours with loss of CDK12 are more likely to respond to immunotherapy, such as Nivolumab (Opdivo) or Pembrolizumab (Keytruda). Their study paves the way for better identification of patients that may benefit from immunotherapy clinical trials.

Poor adherence to active surveillance guidelines in Australia

Active surveillance for men with low-risk, localised prostate cancer aims to avoid or delay treatment until it becomes necessary. A new Australian study has examined data from the Prostate Cancer Outcomes Registry in Victoria to ask how well active surveillance guidelines are being followed. Unfortunately, the results were not very encouraging.

The Australian study asked whether a minimum of three PSA tests and one biopsy were performed over the first 2 years. Among 1635 Victorian men on active surveillance, only 26.5% had the minimum required tests within 2 years of diagnosis. 53.6% of the men had a repeat biopsy within the first two years. Only 36.8% had 3 or more PSA tests within the first 2 years after diagnosis. 5% of men on active surveillance had no PSA tests at all after diagnosis. Whether these men were having MRIs could not yet be answered. Studies from the US and Europe also show that active surveillance guidelines are not being followed well. This could leave many men vulnerable, as they may miss out on vital early treatment if their cancer progresses. It’s not yet clear why these men are missing tests. It might be due to their own choice, or their clinicians, or their health systems failing to follow-up and organise tests.

This study was described in a research blog from June 2018.