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Updates in Oligometastatic Prostate Cancer: A Multidisciplinary Perspective

Dr. Bruno Bastos, from Miami Cancer Institute, presents during the first-ever US-based ESMO Conference – 2022 ESMO Florida.

In the first-ever ESMO Review session held in the United States, Dr Bruno Bastos from Miami Cancer Institute provided an overview of what is currently a controversial and multidisciplinary topic, treatment approaches for oligometastatic prostate cancer. As a foundation of his discussion, Dr Bastos first emphasized the difference between synchronous metastasis, that is, a patient who presents upfront with de novo metastatic disease and low volume of disease, and metachronous metastases, occurring in, for example a patient initially treated with surgery and/or radiotherapy who develops metastases at a later time. An important point he emphasized is that patients with de novo metastatic disease have a worse prognosis, relative to those who develop metastatic disease at a later time. He briefly outlined the next-generation imaging technique of prostate-specific membrane antigen positron emission tomography (PSMA-PET) and noted its greater sensitivity to detect metastatic disease, as compared with conventional imaging techniques. In his presentation, Dr Bastos considered updates from the ESMO 2022 Congress from three different clinical perspectives, surgery, radiology, and oncology.

From the surgical perspective, Dr Bastos noted that due to its poor prognosis, surgery is currently not recommended for synchronous metastases, but only for metachronous metastases. He noted that modern imaging techniques have helped to improve staging, and that in Europe, PSMA-PET is now widely used in all scenarios. Based on results from the STAMPEDE trial, intensified hormonal therapy plus radiation to the primary site (not the metastatic site) is the current standard of care. He noted that currently there is limited data showing a benefit of radiation to the metastatic site. Dr Bastos also emphasized that radical prostatectomy (RP) is now rarely indicated for patients with de novo (i.e., synchronous) metastases due to the poor outcomes relative to metachronous metastases, and he further noted the very high incidence of troublesome complications such as incontinence occurring as a result of RP.

From the radiation oncologist perspective, Dr Bastos noted that based on the results of the STAMPEDE trial, improvement in survival is limited to patients receiving hormonal therapy plus radiotherapy to the primary site, and only in those with a low metastatic burden, defined as < 3 metastatic sites, whereas for those with > 3 sites, there was no benefit. In considering what to do for patients with nodal recurrence, Dr Bastos noted this was a very common discussion at tumor boards, for example, to radiate or not with single-beam radiotherapy (SBRT) for patients with 1 or 2 positive lymph nodes. He noted there was no data to this effect available for patients with synchronous metastases, while for metachronous metastases, data were available but were limited and retrospective in nature. In particular, he noted the STOMP and ORIOLE trials, 2 small phase II studies (~100 patients) which showed a progression-free survival (PFS) benefit with SBRT for patients with up to 3 nodal lesions, but no overall survival (OS) benefit, no improvement in time to castration-resistant prostate cancer (CRPC), and no improvement in radiographic PFS.

Another question considered in ORIOLE and STOMP trials was whether there was a patient population that did not benefit from SBRT/observation. In this regard, Dr Bastos outlined an analysis whereby patients were divided into those with high-risk somatic germline mutations (ATM, BRCA 1/2, RbA, or TP53) or genomic low risk, on the hypothesis that those with homologous recombination (HR) mutation would not benefit. The results of this analysis showed that there was a benefit of metastasis directed treatment (MDT) in all patients, but those with an HR mutation benefitted even more. Further analyses stratified patients based on androgen receptor activity (ARA) score, and found that those with a low ARA score had significantly more aggressive disease, and worse outcomes following MDT/observation.

Dr Bastos summarized the overall conclusions from the radiologic perspective, noting first, there is a need to distinguish metachronous versus synchronous metastases, second, the data supports irradiating the primary site only, whereas no data exists to suggest benefit of MDT. Third, based on the results of phase II data from ORIOLE and STOMP, MDT may be better than observation if the patient has low disease burden (1 or 2 metastases), and genomic profiling could help to better stratify patients and determine the need for more aggressive androgen deprivation therapy.

From the oncologist perspective, Dr Bastos emphasized that oligometastatic disease in prostate cancer is not clearly defined, although next generation imaging strategies such as PSMA-PET may be helpful to further delineate treatment options in this setting. He noted that oligometastatic disease falls mostly under the heading of low volume disease, and that generally the critical number to remember is up to 3 metastatic sites. He noted that systemic treatment remains the standard of care, and there are many options in this regard, including docetaxel, abiraterone, enzalutamide, and combination therapies. There is strong evidence for the efficacy of systemic combination treatments, and while there may be slightly more data to support the use of MDT, there is no definitive evidence in this regard. Despite this, a survey of oncologists at ESMO 2022 showed that 81% of physicians still favored the use of MDT, noting the difficulty of enrolling patients in clinical trials.

Dr Bastos concluded with a summary of some of the open questions regarding oligometastatic disease in prostate cancer. These included, first, what is the optimal length of treatment; for example, should treatment be continued after 2 to 3 years in patients who are considered “good responders” with systemic therapy? A second issue is the need for a better understanding of disease biology, and whether biomarkers can be better utilized to help stratify patients for more aggressive therapies. Lastly, there is a need to better select patients who might benefit from MDT, and in this regard, advanced imaging technologies like PSMA-PET, time to relapse, and/or genetic predictors may be helpful.

See more from the 2022 ESMO Florida Conference here.

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