Prostate cancer sometimes comes back after surgery or radiotherapy treatment. Men whose scans show that a few small tumours have spread are considered to have oligometastatic prostate cancer. Determining the best treatments for these men is an important research topic at the moment. Two recently published clinical trials have indicated that a radiation-based treatment called SABR can benefit men at this early stage of metastatic prostate cancer.
Stereotactic ablative body radiotherapy (SABR) is a type of radiosurgery. It uses radiation to destroy tumour cells, leaving the surrounding tissue unaffected. It's not the same as conventional radiotherapy. SABR delivers radiation at a very high intensity, all at once, to a small area. It is a high-precision technique that is used to deliver the high dose of radiation to the tumour with millimetre accuracy. SABR treatments are suited to small tumour sizes. So SABR is potentially a good treatment for the few small tumours that are detected in a patient who has oligometastatic prostate cancer.
SABR for men with oligometastatic prostate cancer has now been tested in two clinical trials that finished this year. The STOMP trial tested SABR for men who had not yet started androgen deprivation therapy (ADT). This trial asked whether using SABR could delay the need for ADT. The Australian POPSTAR trial asked whether SABR was a safe and feasible treatment for men with oligometastatic prostate cancer, regardless of previous ADT.
The STOMP trial
The STOMP trial tested treatments directed at the new small tumours. The treatments were SABR and surgery to remove lymph nodes. These treatments are referred to as metastasis-directed therapy, meaning that the treatment is directed to specific sites in the body to target the tumours. This is different from androgen deprivation therapy - these drugs can potentially reach any prostate cancer cells in the body. Metastasis-directed therapy relies on doctors being able to predict or detect the tumour location. For men with oligometastatic prostate cancer, metastasis-directed therapy options include SABR directed at the new tumours, as well as surgery to remove lymph nodes that have tumours (also known as pelvic lymph node dissection).
The STOMP trial tested metastasis-directed therapy compared to surveillance for men with oligometastatic prostate cancer. Men in the treatment group received SABR and/or surgery to remove pelvic lymph nodes with tumours. STOMP stands for Surveillance or metastasis-directed Therapy for OligoMetastatic Prostate cancer recurrence. To compare therapy versus surveillance, the STOMP trial asked if there was a difference in the time taken to start ADT. The STOMP researchers hoped that by using metastasis-directed therapy, these men could safely delay the need to start ADT.
The STOMP trial was a phase 2 randomised controlled trial conducted at 6 different centres in Belgium. 62 men volunteered for this trial, with half allocated therapy and half surveillance. The men in this trial had prostate cancer that returned despite surgery or radiotherapy. They had 3 or less small tumours detected. After therapy or surveillance was started, they were follow-up by the study for an average of 3 years.
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 therapy 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 SABR were "looser stools" in one patient and temporary muscle soreness in another.
The phase 2 randomised STOMP trial provided promising evidence to support using SABR and/or lymph node surgery to treat early spread tumours to delay the need for ADT. But this small trial, with a narrow selection of patients, needs to be upscaled to a large phase 3 trial to provide the level of evidence needed to make metastasis-directed therapy the new standard of clinical care.
The POPSTAR trial
Results from a PCFA-funded Australian trial testing SABR have recently been published in the prestigious journal European Urology. The POPSTAR trial tested the safety and feasibility of SABR for men with oligometastatic prostate cancer. The trial was run by A/Prof Farshad Faroudi from Austin Health and A/Prof Shankar Siva from the Peter MacCallum Cancer Centre in Melbourne.
POPSTAR was a pilot study that followed the progress of men receiving SABR, but did not compare to a control group. POPSTAR stands for Pilot study of patients with Oligometastases from Prostate cancer treated with STereotactic Ablative Radiotherapy.
Men who took part in the POPSTAR trial had previous radiotherapy or surgery treatment for their prostate cancer. Their cancer had returned with up to 3 small tumours detected on scans (oligometastatic stage). These small tumours were spotted in bones or lymph nodes. Some of the men had already started ADT and some had not. These men received treatment of a single dose of SABR directed at each of the small tumours.
The 33 patients receiving SABR were followed for 2 years by the study. During this follow-up period, no patients died, 2 had tumours that spread in the local area and 20 had tumours that spread into distant areas. The trial reported a number of specific measures:
Safety: SABR treatment for these men was considered sufficiently safe to make it a feasible option for treatment. Many of the men experienced mild effects such as fatigue, diarrhoea, and nausea. More serious problems included bone fractures.
Feasibility: Treatment was successfully delivered as planned in 97% of cases. The SABR radiation beam was shown to have hit the tumour targets within 5mm of the planned site.
Local progression-free survival: This refers to how many men remained alive without continued growth of their small tumours. 93% of men in the study did not see these small tumours continue to grow in the 2-year time-period.
Distant progression-free survival: This refers to how many men remained alive without more tumours appearing in new sites. A year into the study this proportion was 58%. By the end of the 2-year time-period 39% of the men did not have new tumours.
PSA response: 26 of the 33 men saw their PSA level drop after the SABR treatment. 7 of them had their PSA drop to an undetectable level.
Quality-of-life: Quality-of-life was investigated by surveys at regular intervals. Questions were asked about factors such as side effects, pain, physical and emotional effects. Results from these surveys indicated that quality of life for the men in this trial remained similar throughout the 2-year period but some experienced more pain as time went on.
Over 1/3 of the patients in this trial did not see their cancer progress and did not need ADT over the 2-year trial period. Long-term follow-up will be needed to ask how long this treatment can hold back the tumours.
Like the STOMP trial, the POPSTAR trial showed that SABR was a safe and feasible treatment for men with oligometastatic prostate cancer. Ideally, SABR will now be tested in a phase 3 randomised controlled trial for men with oligometastatic prostate cancer. These are men who have only a few small tumours return after initial treatment. A larger trial for a longer time period is necessary to determine the length of time that SABR stops tumours growing.
PCFA is proud to have supported the POPSTAR clinical trial, through funding from The Movember Foundation.
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