Urgent guideline changes needed to improve treatment access for newly diagnosed Metastatic Prostate Cancer
Urgently needed updates to NICE Guidelines
In 2023 NICE approved the novel hormonal agent (NHA) (sometimes referred to as an Androgen Receptor Pathway Inhibitor (ARPI) )darolutamide for use in combination with androgen deprivation therapy (ADT) and chemotherapy for men with newly diagnosed hormone sensitive metastatic prostate cancer.
The ARASENS trial - an international, randomised, double-blind, placebo-controlled phase III study - showed that by adding darolutamide to ADT and docetaxel (Triplet), it reduced the likelihood of death over 3.5 years by a third. By 4 years, 12% (~1 in 8) more patients were alive if they had received darolutamide in addition to chemotherapy and ADT.
This treatment combination also prolonged time to PSA rising (a marker of resistance to hormone therapy), time to pain development and need for painkillers, time to bone metastases, and time to needing to start a different cancer treatment.
The exact patients who gain this benefit from this treatment ‘intensification’ appear to be those with higher-risk (more aggressive) and higher volume (more metastases) prostate cancers.
In men who are not suitable for or are less likely to benefit from Triplet therapy, there are several trials (such as LATITUDE, STAMPEDE, TITAN, ENZAMET and ARCHES) showing clear benefit in the addition of various NHAs to ADT. These treatments are general well tolerated and often defer or avoid the need for chemotherapy.
Our specialist nurses have recently taken calls from men who have questioned the treatment that their oncologist has recommend for their newly diagnosed, metastatic, prostate cancer.
These men have been offered docetaxel and ADT alone; numerous international experts and guidelines strongly advocate against this approach.
For example, EAU guidelines 6.6.5 state: Since the data of the phase III triplet therapy trials (ARASENS) have been reported, docetaxel as sole addition to ADT is no longer a valid option in the majority of patients if an NHA is available and there are no contra-indications to use one.
Unfortunately, NICE guidelines currently do not reflect their own 2023 approval of triplet therapy and still only refer to offering chemotherapy in this group of men. NG13 1.5.6 states: Offer docetaxel chemotherapy to people with newly diagnosed metastatic prostate cancer who do not have significant comorbidities. It is worrying that some clinicians are still referring to these very out of date guidelines considering how many more treatments are now available for men in this indication.
It is clear that patients who could benefit from chemotherapy should be offered triplet therapy, with the pros and cons outlined by a clinician so an informed choice can be made. Specifically, patients should be aware that triplet therapy has a clear survival benefit over other treatments at this stage, but treatment choice at a later stage in the pathway might be diminished. If patients have contra-indications to chemotherapy or are less likely to benefit, doublet therapy in the form of an ARPI and ADT should be offered.
All NHAs approved by NICE which are available to men in the metastatic hormone sensitive setting can be found here. Abiraterone which is approved on an interim basis by NHS England can be found here.
