Discussion
tumor, prostate cancer, tumors, mCRPC, prostate cancers
TUMOR, TUMORS, SOLID TUMORS, PROSTATE CANCER
In this pioneering mCRPC clinical trial, CryoIT was found to be safe and tolerable. This is consistent with the well-defined safety profile of cryoablation in solid tumors [For the total cohort, PFS was 10.5 months while median OS was 40.7 months. In this early phase trial, no controls were included. In a study including mCRPC patients with diverse risk profiles, median PFS were 11.1 months (IQR 3.7–21.8) versus 8.2 months (3.5–16.6) in the less detrimental and more disadvantageous group, respectively, while corresponding OS were 41.8 (23.4–53.6) and 28.4 (17.9–41.9) months [The associations discovered in this trial between CTC response and PFS in prostate cancer correspond with previous findings in phase III trials, where either conversion from CTC counts ≥ 5 to CTC < 5 or total disappearance indicated favorable responses to therapy [The high proportion of expanded or new TCR clonotypes in blood, both two and six weeks after CryoIT, and the minimal intrapatient clonotype overlap could imply an treatment-related expansion or generation of TCR clonotypes with a time-dependent broadening of the peripheral clonotype repertoire. Several recent publications have found that expanded clonotypes in peripheral blood following immune checkpoint inhibition were different from pre-treatment tumor-infiltrating T-cell clonotypes and seemed to be replenished from outside of the tumor [Patients reported consistently high values in the functional and Global Health Status/HR-QoL domains and low values in symptom domains, but those with pre-treatment CTC reported a worse HRQoL over time. In contrast to other trials [All the patients had MSS tumors with low TMB. This finding is in accord with previous studies identifying 1–2% of prostate cancers as MSI and/or TMB high [This work may be limited by a small sample size, and lack of sequential tumor biopsies and comparator groups. While utilization of low doses of cyclophosphamide could impact the CTC numbers, the doses applied are considerably lower than those required for a general cytotoxic effect. We applied imaging guidelines published prior to trial commencement in 2015. As guidelines were updated as new treatment and technologies developed during the trial period, the application of older versions could limit interpretation of radiologically based outcomes. Second line hormonal treatment and early chemotherapy was fully introduced in Norway during the enrolment period and time-to-event comparisons with historical controls will therefore be imprecise. Despite these limitations, the findings encourage a next phase CryoIT trial, powered to estimate potential treatment efficacy.In conclusion