APCCC 2022: What Is the Evidence of Systemic Therapies (Alone or in Combination With MDT) in Oligometastatic 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. Taplin discussed the role of systemic therapy in this disease state. She began by emphasizing the somewhat wide definitions of oligometastatic disease, highlighting that, like pornography, she “doesn’t know how to define it, but I’ll know it when I see it”. Prior expert consensus at the APCCC included the ability to deliver ablative therapy with curative intent” as a key component of the definition. Notably, she noted that, in her view, patients with liver metastases could still have oligometastatic disease.

She further noted that there are alternative assessments of disease burden including the CHAARTED low risk category (defined based on three or fewer bone metastases) and the LATITUTDE low volume category (sharing the same definition). In these trials, this subset comprised 35% and 25% of the cohort respectively.

Considering treatment options for patients with oligometastatic hormone sensitive prostate cancer, she noted that ADT alone has been the standard of care for nearly 70 years. However, treatment intensification is now the standard of care. In low volume disease which may be more dependent on androgen receptor signalling, novel androgen axis targeting agents including abiraterone, enzalutamide, and apalutamide are indicated now as standard of care. Additionally, we can consider the role of ablative therapy either alone (with the goal of delaying the initiation of systemic therapy / ADT), with ADT, or with ADT and systemic treatment intensification. However, she noted that in the development of all these treatment paradigms, it is not entirely clear the degree to which metastatic disease is defined by conventional imaging or PSMA-PET imaging.

To contextualize this discussion, she noted results of the PR7 trial examining continuous versus intermittent androgen deprivation therapy for patients with biochemical recurrence (and absolute PSA levels of at least 3 ng/mL) following radiotherapy. With a median overall survival of 8 years, the majority (60%) of deaths were due to non-prostate cancer causes. She suggested that outcomes may be similar for patients with metachronous low-volume disease.

She highlighted many relevant questions in the care of patients with oligo-metastatic HSPC, emphasizing that we don’t have data to address most of these:

1. Can a proportion of these men be cured? If so, who are they?
2. Which treatments should be given in which combinations to which patients? This highlights the need for validated biomarkers to direct therapy.
3. Can systemic therapy be delayed and, if so, in whom?
 4. What is the optimal duration of systemic therapy in this setting?
5. Is there an upper limit in the number of metastatic sites in which metastasis-directed therapy can be considered as part of the treatment paradigm?

In terms of systemic therapy for patients with low-volume HSPC, she noted that post hoc analysis of STAMPEDE and pending data from ENZAMET (to be presented at ASCO 2022) have shown that novel hormonal therapies improve overall survival. The data supporting improved radiographic progression free survival is even more robust, including STAMPEDE, LATITUDE, ENZAMET, ARCHES, and TITAN trials supporting the role of abiraterone, enzalutamide, and apalutamide, respectively. Given this data, she opined as to whether these novel hormonal treatments should be considered the backbone of therapy, thus forming part of the control arm of any trials of metastasis-directed therapy.

Considering a recent review of the literature, she noted that there are 41 trials in oligometastatic prostate cancer, though few of these are phase III trials. Notably, PET-CT was used for lesion detection in approximately 60% while the remainder rely on conventional imaging. In terms of systemic therapy, this is including in only 50% of trials of which 29% use ADT and the remainder use some combination of chemotherapy, immunotherapy, novel hormonal therapies, or radium-223. 

She then discussed three “potentially practice changing” studies, beginning first with the PLATON trial. This Canadian Cancer Trials Group study is enrolling 410 patients with 5 or fewer bone metastases and randomizing them to receive standard systemic therapy with local ablative therapy to the prostate or ablative therapy to all sites of disease with a primary endpoint of failure free survival.

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She next discussed PEACE V (STORM), a French trial of 178 patients with 3 or fewer oligorecurrent pelvic nodal metastases who are randomized to receive 6 months of ADT with ablative therapy to the prostate with or without whole pelvis radiotherapy.

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Finally, she discussed the VA STARPORT trial which is enrolling men with oligometastatic prostate cancer with 1 to 5 PET-detected lesions and randomizing them to receive standard systemic therapy with or without PET-directed local therapy to all sites of disease.

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She further noted the UNICANCER and SWOG 1802 trials which are assessing similar questions regarding the role of additional local treatment to systemic therapy in metastatic disease.

In terms of treatment recommendations, she suggested using ablative therapies to all disease sites with the least treatment burden along with ADT for two years and consideration of adding abiraterone, enzalutamide, or apalutamide. At two years, if the PSA is undetectable and there is no radiographic evidence of disease, she suggested stopping ADT. In terms of the choice to add novel hormonal therapies, she suggested that this may not be needed for patients who have disease on PET imaging that is not apparent on conventional imaging but should be added for those who have metastatic disease on conventional imaging.

Moving forward, she noted that the study of oligometastatic disease represents a unique subset. Currently, there remains a need to better understand the biology within this disease space to guide biomarker design and discover and identify optimal treatment approaches.

Presented by: Mary Ellen Taplin, MD, Medical Oncologist, Dana-Farber Cancer Institute

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.