AUA 2018: Overall Survival in Patients with Primary Bone Metastatic Prostate Cancer Receiving ADT or ADT plus Concurrent Radiation Therapy: HORRAD Trial

San Francisco, CA USA ( Herein, we report on the first presentation of the HORRAD trial – the first multi-center randomized controlled trial looking at the role of treatment of the primary prostate cancer malignancy in the setting of metastatic disease – to date, no other trials have reported on this clinical disease space. These results have been anticipated and were very well-received!

At this time, all discussion of radical prostatectomy or radiotherapy (or any localized treatment) of the prostate in the setting of metastatic (oligometastatic or otherwise) has been limited to retrospective population-level analyses or single-institution case series. While results have been promising, randomized clinical data has been severely lacking!

In this multi-center, randomized clinical trial from the Netherlands, the authors report their results of a study that was first initiated in 2004 – and hence has excellent follow-up data. However, as the study was started in 2004, the clinical scenario and inclusion criteria reflect clinical thinking at the time. This will be important when discussing the findings below.

Inclusion criteria were any man diagnosed with de novo metastatic prostate cancer with bone metastases – bone metastases were diagnosed on bone scan alone. They must have histologically proven prostate cancer (PCa) and osseus metastases on bone scan. No CT scan was required as it was not indicated in the patients without curative intent at that time.
Importantly, they excluded patients with prior earlier treatment for prostate cancer, PSA < 20 ng/mL, and age > 80 years.
* All patients by definition had PSA > 20 ng/mL!

Patients were randomized 1:1 to
1. ADT + EBRT (radiotherapy)
2. ADT + (control group)

Primary endpoint was overall survival. Secondary endpoints were PSA recurrence free survival and quality of life. Cancer-specific survival was not specifically assessed.

Median follow-up for the group was 47 months (~4 years).

Key findings:
1. Median survival was NOT statistically significant: 45 months (EBRT) vs. 43 months (control), HR 0.90, p =0.356
2. In subgroup analyses of patients with PSA less than the median of 142 ng/mL, Gleason score <= 8, and <5 osseus mets – no difference in OS. But, perhaps there is a separation of the curves at 2 years?

The authors point out the following in their discussion:
1. These patients all had HIGH metastatic burden – as, in 2004, there were only included if PSA > 20 ng/mL (median was actually 142!). As such, patients had lots of bony metastatic disease, high PSA. Not representative of the oligometastatic patient of interest in today’s world.
2. Selection was based solely on bone scan – so no data on lymph node or visceral mets. Both of these have significant prognostic implications, so not having this info severely limits the analysis.
3. Patients have such high metastatic burden that local therapy probably has no effect.

However, in the open question session, some important points were brought up:
1. There is a hint of separation in KM curves after 2 years for patients with lower volume disease (PSA < 142, <5 bone mets, and Gleason <= 8). These are still more aggressive than the oligometastatic patients we deal with now, but perhaps this hint of a difference may result in a significant impact down the line.
2. Dr. Briganti asked about the EBRT therapy regimen – it was 70 Gray to the prostate alone, not the nodes. Current treatment paradigms utilize 78-82 Gray, and often include the nodes. So, this change may also have an impact.

Overall, this was an important negative study – but provides some important insight into the problem! Further clinical trials are pending and will hopefully report soon.

Presented by: Liselotte Boevé

Co-Authors: Maarten Hulshof, André Vis, Koos Zwinderman, Jos Twisk, Karl Delaere, Jeroen van Moorselaar, Paul Verhagen, George van Andel

Written by: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto, Twitter: @tchandra_uromd at the 2018 AUA Annual Meeting - May 18 - 21, 2018 – San Francisco, CA USA

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