Circulating tumor cells are strong early signal of prostate cancer recurrence

June 18, 2020

Following radical prostatectomy, circulating tumor cells may indicate an increased risk of recurrence earlier than a PSA rise.

A study found that circulating tumor cells (CTCs) were often detected in patients who had undetectable PSA levels following radical prostatectomy, and these patients with CTCs had an increased risk of biochemical recurrence.

Among 203 patients in the study, CTCs were detected in 36% (n = 73). The 3-year biochemical recurrence-free survival rate from the time of surgery was 81.6% in patients who were CTC-negative compared with 48.9% in patients who were CTC-positive, representing a statistically significant difference (P <.001).

“Circulating tumor cells in the blood were frequently detected in patients with undetectable prostate specific antigen levels after radical prostatectomy for localized prostate cancer. Furthermore, circulating tumor cell detection was associated with an increased risk of biochemical recurrence, suggesting that circulating tumor cell detection precedes prostate specific antigen rise after surgery in cases of prostate cancer recurrence. Large-scale validation is needed in the future,” the investigators wrote.

The study enrolled 218 patients with prostate cancer who had received radical prostatectomy between February 2014 and July 2016. Exclusion criteria removed 15 patients from the analysis.

Across the overall 203-patient analysis population, the median patient age was 66 and the median preoperative PSA level was 7.70 ng/ml (IQR, 5.20-11.80), with 22 patients having a PSA level ≥20 mg/ml. The mean prostate size was 38.28 cc. The disease stages were T2 (n = 117), T3a (n = 55), T3b (n = 31). Nine patients had lymph node involvement. Patients’ Gleason scores were 6 (n = 55), 3+4 (n = 84), 4+3 (n = 45), 8 (n = 11), and 9-10 (n = 8). Fifty-one patients had a positive surgical margin. Sixteen patients received adjuvant radiotherapy. Seventy-three patients had biochemical recurrence and 9 patients had distant metastasis.

All patients had undetectable PSA concentrations at the time of CTC sampling. The CTC sampling was conducted at a median of 4.5 months after surgery. According to the authors, “Detection of circulating tumor cells in the blood of patients was performed using a novel approach with a replication-competent adenovirus controlled by prostate specific antigen/prostate specific membrane antigen transcription regulatory elements (Ad5/35E1aPSESE4).”

Biochemical recurrence-free survival was the primary end point. The median follow-up time was 41.8 months.

The recurrence-free survival benefit for CTC-negative patients was upheld across subgroups defined by Gleason score, surgical margin status, and pathological stage. Among a 105-patient subgroup with available preoperative CTC data, patients with no detectable CTCs after surgery had better biochemical recurrence-free survival, regardless of whether or not they had preoperative CTCs.

The investigators also conducted a multivariable analysis showing that having CTCs after surgery was independently associated with a higher risk of biochemical recurrence (HR, 5.42; 95% CI 3.24-9.06; P <.001).

“We believe that this analysis of prospectively collected samples provides a valuable contribution as the first study to investigate the role of postoperative CTC analysis in patients who have undergone radical prostatectomy for prostate cancer, regardless of cancer grade and stage. In addition to recent genomic tests and novel imaging modalities, CTC analysis may help support clinical decision making for postoperative management in patients after radical prostatectomy.”

The study was supported by the National Cancer Center, Korea.

Reference

Pak S, Seok Suh Y, Lee D-E, et al. Association between postoperative detection of circulating tumor cells and recurrence in patients with prostate cancer. J Urol. 2020;203(6):1128-1134. doi: 10.1097/JU.0000000000000704