Disseminated Tumor Cells in Prostate Cancer Patients after Radical Prostatectomy and without Evidence of Disease Predicts Biochemical Recurrence

Abstract

Purpose Men with apparently localized prostate cancer often relapse years after radical prostatectomy (RP). We sought to determine if epithelial-like cells identified from bone marrow (BM) in patients after RP (commonly called disseminated tumor cells, DTC) were associated with biochemical recurrence (BR). Experimental Design We obtained BM aspirates from 569 men prior to RP and from 34 healthy men with PSA<2.5 ng/ml to establish a comparison group. Additionally, an analytic cohort consisting of 98 patients after RP with no evidence of disease (NED) was established to evaluate the relationship between DTC and BR. Epithelial cells in the BM were detected by magnetic bead enrichment with antibodies to CD45 and CD61 (negative selection) followed by antibodies to human epithelial antigen (positive selection) and confirmation with FITC-labeled anti-BerEP4 antibody. Results DTC were present in 72% (408/569) of patients prior to RP. There was no correlation with pathologic stage, Gleason grade, or pre-operative PSA. Three of 34 controls (8.8%) had DTC present. In patients NED post-RP, DTC were present in 56/98 (57%). DTC were detected in 12/14 (86%) NED patients post-RP who subsequently suffered BR. Presence of DTC in NED patients was an independent predictor of recurrence (HR 6.9, CI 1.03–45.9). Conclusions Approximately 70% of men undergoing RP had DTC detected in their BM prior to surgery, suggesting that these cells escape early in the disease. Though pre-operative DTC status does not correlate with pathologic risk factors, persistence of DTC after RP in NED patients was an independent predictor of recurrence.

A Urologist’s Personal View of Prostate Cancer

“…[14,15] However, studies using magnetic resonance imaging have shown a much higher incidence of bone metastatic disease than would be found by the traditional bone scan, [16] and disseminated tumor cells are present in the bone marrow in men with PSA failure with unexpected frequency. [17] These findings also support the distant failure component of PSA recurrence. Observational studies from Stanford demonstrated the benefit of using androgen deprivation and whole pelvic radiation versus prostate bed radiation alone.…”

Secreted Protein Acidic and Rich in Cysteine (SPARC) Mediates Metastatic Dormancy of Prostate Cancer in Bone

“…However, patients often develop fatal recurrent disease months or years after treatment of the primary tumor. The culprits for the recurrent disease are the small number of residual cells that are disseminated from the primary tumor prior to treatment (4). Even patients with asymptomatic disease or no evidence of primary disease progression are known to often harbor cancer cells at distant organs such as bone, and they can be isolated from the bone marrow aspirate (5).…”

Bone marrow as a metastatic niche for disseminated tumor cells from solid tumors

“…Although the mechanisms are yet to be defined, it is generally believed that DTCs can become overt and clinically relevant metastases 63 that lead to disease recurrence even after treatment. 67 Therefore, new approaches to treat bone metastasis are urgently needed. For example, HSC mobilizing drug (for example, G-CSF and AMD3100) can be used to mobilize the niche-engaged dormant DTCs to re-enter the cell cycle.…”