MP79-08 PTEN LOSS IN LOCALIZED PROSTATE CANCER: CLINICOPATHOLOGIC PARAMETERS AND RELATIONSHIP WITH DISEASE OUTCOME

PURPOSE Using nonenrichment-based, potentially more sensitive Epic Sciences circulating tumor cell (CTC) platform, we sought to detect and characterize CTCs in untreated, high-risk localized prostate cancer and to evaluate their clinical implication. METHODS Between 2012 and 2015, blood samples were prospectively collected from patients with National Comprehensive Cancer Network high-risk localized prostate cancer undergoing either radiotherapy (XRT) plus androgen deprivation therapy or radical prostatectomy (RP) with curative intent. Samples were analyzed with the Epic Sciences platform with 4′,6-diamidino-2-phenylindole, CD45, cytokeratin (CK), and androgen receptor (AR) N-terminal staining. CTC counts were correlated with biochemical recurrence (BCR). RESULTS A diversity of CTC subtypes, including CK-positive, CK-negative, AR-positive, and CTC clusters, were observed in 73.3% (33 of 45) of patients with evaluable data. The median follow-up was 14.2 months (range, 0.5 to 43.7 months). BCR occurred more frequently in the RP group than XRT (15 of 26 v one of 19), with most patients in the XRT group continuing to receive androgen deprivation therapy. A higher proportion of metastatic events were observed in the RP group (five of 26 v one of 19). In the RP group, BCR and development of metastases were associated with a higher total number of CTCs, AR-positive CTCs, and CTC phenotypic heterogeneity. One patient who developed BCR and metastases quickly after RP had diverse phenotypical CTC subtypes, and single-cell genomic analyses of all detectable CTCs confirmed common prostate cancer copy number alterations and PTEN loss. CONCLUSION CTCs can be identified in most patients with high-risk localized prostate cancer before definitive therapy using the Epic Sciences platform. If confirmed in a larger cohort with longer follow-up, phenotypic and genomic characterization of CTCs pretherapy may provide an additional means of risk stratifying patients with newly diagnosed high-risk disease and potentially help identify patients who could require multimodal therapy.

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Prostate-specific antigen as a pretherapy prognostic factor in patients treated with radiation therapy for clinically localized prostate cancer.

Journal of Clinical Oncology ◽

10.1200/jco.1993.11.11.2158 ◽

1993 ◽

Vol 11 (11) ◽

pp. 2158-2166 ◽

Cited By ~ 104

Author(s):

T M Pisansky ◽

S S Cha ◽

J D Earle ◽

E D Durr ◽

T F Kozelsky ◽

...

Keyword(s):

Prostate Cancer ◽

Prognostic Factor ◽

Prostate Specific Antigen ◽

Combined Modality Therapy ◽

Clinical Stage ◽

Specific Antigen ◽

Tumor Grade ◽

Localized Prostate Cancer ◽

Disease Outcome ◽

Tumor Relapse

PURPOSE This study was conducted to determine the value of prostate-specific antigen (PSA) as a pretherapy prognostic factor for localized prostate cancer treated with primary irradiation (RT). PATIENTS AND METHODS Between March 1987 and December 1990, 254 patients with pretherapy PSA determinations were treated for clinical stage A2 to C prostate adenocarcinoma. In conjunction with other prognostic factors, pretherapy PSA was evaluated to determine whether it had independent predictive value for disease outcome. RESULTS Pretherapy PSA was highly and directly correlated with clinical stage, tumor grade, and acid phosphatase level. With a median follow-up duration of 24 months, 241 patients (95%) were fully assessable for disease outcome. In these patients, PSA and tumor grade were the sole independent predictive factors for tumor relapse (ie, clinically determined and/or increasing PSA level). The combination of pretherapy PSA and tumor grade information defined groups of patients with distinctly different outcome. For patients in low- (favorable PSA and tumor grade), intermediate- (favorable PSA or tumor grade), and high- (adverse PSA and tumor grade) risk categories, the actuarial rates of survival free of tumor relapse or increasing PSA level were 94%, 77%, and 42% at 3 years, respectively (P < .0001). CONCLUSION Pretherapy PSA is a strongly independent prognostic factor for disease outcome following primary RT. The combination of adverse pretherapy PSA and unfavorable tumor grade identified a cohort of patients with a high risk of early treatment failure in whom combined modality therapy may be appropriately investigated.

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