APCCC 2022: What is the Evidence of MDT in Synchronous vs Metachronous mHSPC?

(UroToday.com) In the session of the 2022 Advanced Prostate Cancer Consensus Conference focusing on the treatment of patients with oligometastatic and oligoprogressive prostate cancer, Dr. Spratt discussed the evidence for metastasis directed therapy (MDT) in patients with synchronous and metachronous metastatic hormone sensitive prostate cancer (mHSPC). In terms of level-setting, he began by highlighting the landscape of oligometastatic cancer, with a focus on the top right corner (synchronous oligometastatic disease, metachronous oligorecurrent or oligoprogressive disease).

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He emphasized that there is essentially no evidence to support of the role of MDT or stereotactic body radiotherapy (SBRT) in patients with synchronous disease. However, there is some evidence for this treatment paradigm in the metachronous setting. This includes a number of small, randomized trials: STOMP (n=62), ORIOLE (n=54), and SABR-COMET (n=99).

He first discussed both STOMP and ORIOLE. These are small, prostate cancer focused randomized controlled trials. In each case, metastatic disease was characterised on the basis of PET imaging whether choline or 18F-DCFPyL PSMA. Patients were then randomized to either observation or metastasis-directed therapy. In both trials, patients who received MDT had improvements in biochemical recurrence/progression which manifest in delays in the initiation of systemic therapy with androgen deprivation therapy. Notably, there was minimal grade 2 toxicity with the addition of ADT.

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SABR-COMET is a larger, pan-cancer trial with relatively good representation of patients with prostate cancer. Dr. Spratt emphasized that it is not clear that we need to study this specifically in prostate cancer. SABR-COMET demonstrated improvements in five-year overall survival for patients who received SABR in addition to standard of care for the management of patients with 1-5 metastatic sites, with a controlled primary.

Dr. Spratt then considered some of the non-randomized evidence regarding this question. Here, there are a growing number of studies assessing this treatment paradigm in the synchronous setting. In each case, these are small studies. He first highlighted data from MSKCC in which 20 men with newly diagnosed oligometastatic prostate cancer were treated with local therapy, ADT and SBRT to osseus metastases. One-fifth of these patients achieved undetectable PSA levels after testosterone recovery. Next, he discussed a report of 12 patients treated at Johns Hopkins who had fewer than 5 sites of oligometastatic disease. Treatment in this case included local therapy, chemohormonal therapy, and SBRT to metastatic sites. These authors reported that 67% of patients had undetectable PSA after testosterone recovery at 3 years. In Milan, 39 men with newly diagnosed oligometastatic prostate with 2 of fewer sites of metastatic disease received radiotherapy with ADT and SBRT to osseous disease. At four-years, 47% of patients had recurred, 27% developed further metastases, and 35% developed castration resistance. Finally, in the largest study of 180 men treated with a similar approach at Peking University, the one-year progression-free survival was 94%.

In the metachronous setting, he emphasized that there are “too many” series to highlight. Instead, he focused on two: OLIGOPELVIS and PSMA MRgRT. In particular, he noted that all sites of disease were detected by PSMA-PET in the PSMA MRgRT study. In this context, following MDT, only 22% of patients had biochemical no evidence of disease. Dr. Spratt emphasized that he uses this data for patient counselling, to provide reasonable estimates of outcome when considering this treatment approach.

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Moving forward, he emphasized the need for large randomized trials to address this question. One such trial, in the synchronous setting will come from the STAMPEDE platform trial in which patients will receive standard systemic treatment intensification and radiotherapy to the primary with or without metastasis-directed therapy. With a planned sample size of 1800, this trial will be able to provide overall survival estimates.

He further noted that there are many other larger trials across tumor sites, and pan-cancer sites which may be informative to how we treat patients with prostate cancer.

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In conclusion, Dr. Spratt noted that there is no randomized evidence to support metastasis-directed therapy in patients with synchronous oligometastatic hormone sensitive prostate cancer. However, there is phase II data to support an improved progression-free survival for patients with metachronous disease. This approach warrants further testing to quantify the benefit and assess the ability of MDT to avoid continuous systemic therapy.

Presented by: Daniel Spratt, MD, Chairman and Professor of Radiation Oncology at University Hospitals (UH) Seidman Cancer Center and Case Western Reserve University

Written by: Christopher J.D. Wallis, University of Toronto Twitter: @WallisCJD during the 2022 Advanced Prostate Cancer Consensus Conference (APCCC) Annual Hybrid Meeting, Lugano, Switzerland, Thurs, Apr 28 – Sat, Apr 30, 2022.