(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. Jones presented the final talk of this year’s APCCC meeting discussing whether “oligoprogressive” prostate cancer exists as a distinct clinical entity.
To contextualize this discussion, he provided photographic “evidence” of the presence of the Loch Ness monster, suggesting that what we think we see may not represent the whole truth. He then noted that there is a general lack of consensus on the definition of oligoprogressive disease, though he utilized a definition of “a state where after an initially successful systemic therapy of disseminated metastases, a single/few lesions display further progression”. Mechanistically, this definition is consistent with an etiology in which one or more subclones evolve which are resistant to the ongoing systemic therapy. Thus, a therapeutic rationale for treatment of these sites is “compelling” given this proposed etiology.
However, he noted, there is no direct evidence to support the presence of this disease entity in prostate cancer. There is some supportive evidence showing evidence of subclones emerging following therapy. However, the overall underlying biology of oligoprogression remains poorly understood and is confounded by weaknesses inherent in imaging in which we are unable to see all drug-resistant sites of disease/clones.
However, using conventional imaging, he cited a case of a man who had near total regression of wide spread metastatic disease while on systemic therapy, followed by the development of one or two new metastatic sites. In a retrospective study of 102 patients treated at Royal Marsden, who received androgen receptor targeted agents, 20 patients did not have evidence of disease progression during the study interval, 52 had poly-progressive disease and 30 had oligo-progressive disease. Among these 30, 21 were deemed suitable for SBRT, representing approximately 20% of the overall study population and 25% of those with progressive disease.
He then cited data from a number of small, retrospective series assessing outcomes of treating these patients with lesion-directed therapy, typically SBRT. In most cases, there are meaningful PSA response rates, suggesting that a large burden of the active disease has been treated with this local therapy approach. In doing so, some studies have shown that the time to next systemic therapy may be approximately 20 months, following this initial progression event. However, taken together, he suggested that this “background of data” suggests a “marginal” benefit.
There is, however, prospective data currently being generated, including the TRAP study which will examine outcomes from SBRT in patients with oligoprogression at one or two metastatic sites following androgen receptor pathway inhibition.
The MEDCARE study will address a similar question using both surgery or SBRT with an endpoint of next systemic therapy free survival. However, apart from the clinical endpoints, Dr. Jones suggested that the exploratory endpoints of each trial, including whole body MRI response, ctDNA, and longitudinal PSMA-PET imaging, may be more informative.
In conclusion, he highlighted that he believes that oligoprogression exists, though it is poorly defined with current imaging approaches. While imaging is critical to guiding lesion-directed therapy, a better understanding of the biology of systemic therapy resistance is needed, given its central role in the therapeutic hypothesis. In terms of treatment, he noted that SBRT is generally well tolerated though not all patients will be eligible. However, there is a lack of robust data to support this approach and we are “some way off” this being considered a standard treatment approach.