San Francisco, California (UroToday.com) At the session on Targeted Therapy in the Context of Low-Volume Metastatic Prostate Cancer at the 2020 Genitourinary Cancers Symposium, Professor Piet Ost presented 5-year updated results of the STOMP trial.
STOMP is a phase II randomized controlled trial designed to answer whether metastasis-directed therapy is beneficial for men who have “metachronous oligorecurrent prostate cancer”, a distinct cancer state the importance of which is gaining increased recognition.1 For the purposes of this trial, Dr. Ost defined these state as being present in men who meet the following criteria:
- Completed therapy to the primary tumor with curative intent with either prostatectomy, radiation, surgery followed by salvage/adjuvant radiation
- Biochemical recurrence
- 1-3 extracranial metastases demonstrated on a choline-PET scan (including nodal metastases)
- A multiparametric MRI or biopsy of the prostate bed which was negative for local recurrence of disease
To be eligible for this trial, men were also required to be asymptomatic and to not have had any prior therapy. Specifically:
- No androgen deprivation therapy after or at the time of biochemical recurrence
- No cytotoxic chemotherapy after biochemical recurrence
- No symptoms attributable to the metastatic disease
- Testosterone >50 ng/mL
Enrolled patients were randomized to surveillance or metastasis-directed therapy. Dr. Ost emphasized that the standard-of-care arm underwent surveillance in this case because the European Association of Urology guidelines in 2011 when the trial was designed considered observation (rather than immediate ADT) to be an option in men with asymptomatic metastatic prostate cancer.
All patients underwent PSA testing every 3 months and choline PET scans were repeated at PSA or symptomatic progression.
Patients randomized to MDT underwent excision of lymph node metastases. Extra-nodal metastases were either excised or treated with SBRT (30 Gy in 3 fractions).
The primary endpoint was ADT-free survival. ADT was initiated if there was
- Symptomatic progression OR
- Progression to >3 metastases OR
- Local progression of the baseline detected metastases
The STOMP trial’s initial results were published in the Journal of Clinical Oncology in 2018. 62 patients were enrolled. A significant improvement in median ADT-free survival was seen in the MDT group (13 vs 21 months p=0.11), acknowledging that the p-value threshold for significance was set at 0.20 for this phase II trial.
With these updated results, Dr. Ost’s groups re-affirms their previous findings, this time demonstrating a 5-year ADT-free survival of 8% for the surveillance group and 34% for the MDT group (HR 0.57 [80% CI: 0.38-0.84], log-rank p = 0.06).
This result is difficult to apply to clinical practice for at least two reasons which Dr. Ost acknowledged. First, choline PET is not routinely utilized in this setting. Second, it is unclear whether surveillance (vs ADT or ADT + abiraterone) should be considered the standard of care for men in this population. Certainly, for men with oligometastatic disease on conventional imaging observation is not the standard of care.
The triggers chosen to initiate ADT, especially #2 and #3 above, may also bias the study towards not initiating ADT in the MDT group.
A very interesting secondary finding which Dr. Ost highlighted, however, is the difference in 5-year castrate-resistant prostate cancer free survival rate of 54% vs 76% (hazard ratio 0.62 [80% CI: 0.35−1.09]; p = 0.27). Although it did not reach statistical significance, even by the looser 0.20 cutoff set by the study group, it does numerically favor MDT in this much more meaningful clinical endpoint. This, along with the very low toxicity of MDT (0 grade 2-5 events) and the overall good prognosis of this population in general (median survival 5.3 years IQR 4.3-6.3), does lend further evidence MDT is worth further study in the population.
Presented By: Piet Ost, MD, PhD, Assistant Professor, Ghent University Hospital, Ghent, Belgium
Written by: Marshall Strother, MD, Society for Urologic Oncology Fellow, Division of Urologic Oncology, Fox Chase Cancer Center, Philadelphia PA @mcstroth at the 2020 Genitourinary Cancers Symposium, ASCO GU #GU20, February 13-15, 2020, San Francisco, California
References:- Guckenberger M, Lievens Y, Bouma AB, et al. Characterisation and classification of oligometastatic disease: a European Society for Radiotherapy and Oncology and European Organisation for Research and Treatment of Cancer consensus recommendation. Lancet Oncol. 2020;21(1):e18-e28.