Detection of ctDNA in plasma of patients with clinically localised prostate cancer is associated with rapid disease progression

Abstract

Background DNA originating from degenerate tumour cells can be detected in the circulation in many tumour types, where it can be used as a marker of disease burden as well as to monitor treatment response. Although circulating tumour DNA (ctDNA) measurement has prognostic/predictive value in metastatic prostate cancer, its utility in localised disease is unknown. Methods We performed whole-genome sequencing of tumour-normal pairs in eight patients with clinically localised disease undergoing prostatectomy, identifying high confidence genomic aberrations. A bespoke DNA capture and amplification panel against the highest prevalence, highest confidence aberrations for each individual was designed and used to interrogate ctDNA isolated from plasma prospectively obtained pre- and post- (24 h and 6 weeks) surgery. In a separate cohort (n = 189), we identified the presence of ctDNA TP53 mutations in preoperative plasma in a retrospective cohort and determined its association with biochemical- and metastasis-free survival. Results Tumour variants in ctDNA were positively identified pre-treatment in two of eight patients, which in both cases remained detectable postoperatively. Patients with tumour variants in ctDNA had extremely rapid disease recurrence and progression compared to those where variants could not be detected. In terms of aberrations targeted, single nucleotide and structural variants outperformed indels and copy number aberrations. Detection of ctDNA TP53 mutations was associated with a significantly shorter metastasis-free survival (6.2 vs. 9.5 years (HR 2.4; 95% CIs 1.2–4.8, p = 0.014). Conclusions CtDNA is uncommonly detected in localised prostate cancer, but its presence portends more rapidly progressive disease.

Prognostic and Predictive Value of Circulating Tumor DNA in Patients with Advanced Colorectal Cancer and Chemotherapy

“…These results support that plasma ctDNA ngerprints is a potential predictive biomarker of chemotherapy in late stage CRC, in line with our previous report in pan-cancer [18]. Our ndings were similar to other studies in the literature on ctDNA and systemic therapies in prostate cancer [35], advanced stage melanoma [36], non-small cell cancer [37] and gastric cancer [38], which all showed that the patients with detectable ctDNA had an extremely rapid disease progression and recurrence risk. It also provides a concept that raising individual treatment strategies are necessary to strive more effective clinical outcomes for patients with high ctDNA concentration.…”

Tumor DNA From Tumor In Situ Fluid Reveals Mutation Landscape of Minimal Residual Disease After Glioma Surgery and Risk of Early Recurrence

“…Many studies have found that circulating tumor DNA (ctDNA) is a reliable biomarker for residual tumor diseases and can be used to identify high-risk patients with tumor recurrence. These findings have been confirmed in tumors outside the nervous system, such as breast cancer (12), colon cancer (13), lung cancer (14,15), esophageal cancer (16), and prostate cancer (17). But because of the existence of blood-brain barrier, the detection of ctDNA in blood is very limited.…”

The use of fulvestrant before chemotherapy improves survival in hormone-positive breast cancer: a real-life study

“…Baseline demographic features (age, sex, menopause status), histologic subtypes, HER-2 expression status, tumor grades, patterns of metastases (visceral, soft tissue, bone), endocrine sensitivity status (primary resistance, secondary resistance, and endocrine sensitive), the use of trastuzumab with fulvestrant and previous lines of treatment before fulvestrant recorded together with the best response under treatment, date, and pattern of progression under fulvestrant, clinical benefit rate 8 and survival data. Endocrine sensitivity was categorized according to the definitions in the 5th ESO-ESMO international consensus guidelines for advanced breast cancer (ABC5) guideline, 9 and CBR was defined as the best response of complete response, partial response, or stable disease lasting more than 24 weeks as suggested in the previous clinical trials.…”