Treating Oligometastatic Hormone-Sensitive Prostate Cancer
Atish Choudhury, MD, PhD, Dana-Farber Cancer Institute, Boston, Massachusetts, discusses a case of oligometastatic hormone-sensitive prostate cancer, exploring the role of metastasis-directed therapy combined with intensified androgen deprivation.
Dr Choudhury highlights how integrating stereotactic body radiation therapy (SBRT) with time-limited androgen deprivation therapy (ADT) and androgen receptor pathway inhibition may prolong treatment-free intervals and deepen disease control in selected patients.
Transcript:
My name is Atish Choudhury and I’m a medical oncologist at Dana-Farber Cancer Institute with a focus on genitourinary malignancies. I’ll be talking about a case of advanced prostate cancer today.
This is a 64-year-old male who has a history of Gleason 4+3=7 prostate cancer for which he underwent radical prostatectomy about a year prior to seeing me. At the time of surgery, he had negative surgical margins but his postoperative PSA was 0.75. He received salvage radiation therapy without androgen deprivation and the PSA continued to rise up to 2.29. He underwent imaging and CT and bone scan both showed unequivocal metastasis in the sternum with no other sites of disease.
So the polling question here is: what treatment strategy would you recommend for this patient?
A. Metastasis-directed therapy with SBRT alone.
B. SBRT with time-delimited ADT alone.
C. SBRT with time-delimited ADT plus an ARPI.
D. SBRT with continuous ADT plus ARPI.
E. Systemic therapy with continuous ADT plus ARPI alone.
And the answer is: all of the above are completely reasonable considerations based on the data that we currently have.
The data around metastasis-directed therapy alone come from the STOMP and ORIOLE trials, where patients were treated with SBRT to sites of disease, and the primary end point was delaying initiation of ADT. If this patient is most interested in delaying androgen deprivation, then SBRT alone would be a reasonable approach. However, we do not really have randomized phase 3 data showing that SBRT alone prolongs survival in this setting.
What randomized phase 3 trials do show is that in patients with metastatic prostate cancer, the addition of an ARPI to ADT improves survival compared to ADT alone, even in patients with low-volume metastatic disease. Systemic therapy with continuous ADT plus ARPI would also be a very reasonable option based on level 1 evidence. There have also been many retrospective studies using SBRT in this setting either with ADT alone or ADT plus ARPI and are being tested with continuous ADT plus ARPI in a number of randomized phase 3 trials.
The data supporting ADT with SBRT primarily come from the RADIOSA trial, where patients were randomized to receive 6 months of ADT with SBRT and that study did show prolongation until clinical progression. However, the prolongation was not particularly dramatic– there was no obvious long-term tail on the curve. The SOLAR and SATURN trials used time-delimited ADT and ARPI in conjunction with SBRT to sites of disease. In particular, the SOLAR trial demonstrated in de novo disease that a large proportion of patients remained treatment-free for several years after the end of treatment. That is a common strategy that is being used, although there is not yet much level 1 evidence demonstrating a survival advantage to using SBRT and or intensified androgen deprivation in this setting.
For this particular patient, he was started on leuprolide plus abiraterone and prednisone and he underwent SBRT to the sternal metastasis. His PSA decreased to less than 0.02. After two years of treatment, the PSA remained undetectable and imaging showed no active disease. At that point, we made the decision to stop the leuprolide and abiraterone. The testosterone normalized 9 months after completion of systemic therapy, although he did become hypogonadal with testosterone levels ranging between 100 and 150 ng/dL.
Six months after completion of treatment, the PSA remains completely undetectable at less than 0.02 despite initial testosterone normalization, suggesting a prolonged treatment-free interval with this aggressive upfront approach.
What this means in terms of managing individual patients moving forward is still not well understood but, I think we need to discuss the risks and benefits of each approach. SBRT alone is likely to delay time to androgen deprivation therapy, but probably not lead to prolonged treatment-free intervals. Continuous systemic therapy is likely to prolong survival in patients who achieve deep PSA responses, but that comes with the toxicity of continuous treatment.
Whether this kind of multi-pronged approach using SBRT with intensified androgen deprivation can lead to favorable long-term outcomes in a broader subset of patients remains to be demonstrated in randomized trials moving forward.
