Interrogating Metastatic Prostate Cancer Treatment Switch Decisions: A Multi-institutional Survey

Lorente, David; Ravi, Praful; Mehra, Niven; Pezaro, Carmel; Omlin, Aurelius; Gilman, A.; Miranda, Miguel; Rescigno, Pasquale; Kolinsky, Michael; Porta, Núria; Bianchini, Diletta; Tunariu, Nina; Perez, Raquel; Mateo, Joaquín; Payne, Heather; Terstappen, Leon W.M.M.; IJzerman, Maarten Joost; Hall, Emma; Bono, Johann S. de

doi:10.1016/j.euf.2016.09.005

Cited by 19 publications

(20 citation statements)

References 31 publications

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“…In the management of CRPC patients, adequate response to therapy is challenging as the traditional Response Evaluation Criteria in Solid Tumors [ 11 ] frequently cannot be applied. The presence or absence of CTCs has emerged as a powerful biomarker to assess prognosis and therapy response [ 1 – 5 ]. Although the CTC numbers measured are extremely low, several ring studies have been conducted and demonstrated the robustness of the test, though a certain level of operator bias cannot be completely eliminated [ 12 – 15 ].…”

Section: Discussionmentioning

confidence: 99%

“…Although the CTC numbers measured are extremely low, several ring studies have been conducted and demonstrated the robustness of the test, though a certain level of operator bias cannot be completely eliminated [ 12 – 15 ]. In the original studies conducted with the CellSearch system, patient groups were divided in those with less or more than 5 CTCs per 7.5 mL of blood and shown to have different clinical outcomes [ 1 – 5 ]. However, recently it was demonstrated that the actual number of CTCs -and not just a count above or below a selected cut-off value- is of importance in order to assess response to therapy [ 4 , 5 , 15 ].…”

Section: Discussionmentioning

confidence: 99%

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Circulating tumor cells, tumor-derived extracellular vesicles and plasma cytokeratins in castration-resistant prostate cancer patients

et al. 2018

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PurposeThe presence of Circulating Tumor Cells (CTCs) in Castration-Resistant Prostate Cancer (CRPC) patients is associated with poor prognosis. In this study, we evaluated the association of clinical outcome in 129 CRPC patients with CTCs, tumor-derived Extracellular Vesicles (tdEVs) and plasma levels of total (CK18) and caspase-cleaved cytokeratin 18 (ccCK18).Experimental DesignCTCs and tdEVs were isolated with the CellSearch system and automatically enumerated. Cut-off values dichotomizing patients into favorable and unfavorable groups of overall survival were set on a retrospective data set of 84 patients and validated on a prospective data set of 45 patients. Plasma levels of CK18 and ccCK18 were assessed by ELISAs.ResultsCTCs, tdEVs and both cytokeratin plasma levels were significantly increased in CRPC patients compared to healthy donors (HDs). All biomarkers except for ccCK18 were prognostic showing a decreased median overall survival for the unfavorable groups of 9.2 vs 21.1, 8.1 vs 23.0 and 10.0 vs 21.5 months respectively. In multivariable Cox regression analysis, tdEVs remained significant.ConclusionsAutomated CTC and tdEV enumeration allows fast and reliable scoring eliminating inter- and intra- operator variability. tdEVs provide similar prognostic information to CTC counts.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Circulating tumor cells, tumor-derived extracellular vesicles and plasma cytokeratins in castration-resistant prostate cancer patients

et al. 2018

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“…Circulating tumor cell analysis may play an important role as a 'liquid biopsy', which will allow physicians to follow changes of the systemic part of the disease over time, enabling adjustment of treatment and thus a promising new diagnostic tool for patients suffering from e.g., breast cancer (36). The majority of the procedures have, however, been hampered by the paucity of these cells recovered by the different approaches particularly those using magnetic bead enrichment after a fixation step (38), which impedes statistical analysis of the circulating tumor cells (39). Apart from mere quantitative analysis, current research on circulating tumor cells is focusing on the identification of novel diagnostic and therapeutic biomarkers expressed by these cells, such as B7-H3 and Ki-67 on tumor cells circulating in the blood, which allows for the determination of the aggressiveness of the residual tumor load, and can thus contribute to the determination of prognosis.…”

Section: Discussionmentioning

confidence: 99%

B7-H3 on circulating epithelial tumor cells correlates with the proliferation marker, Ki-67, and may be associated with the aggressiveness of tumors in breast cancer patients

Pizon¹,

Schott²,

Pachmann³

et al. 2018

Int J Oncol

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Circulating epithelial tumor cells (CETCs) in peripheral blood are a prerequisite for the development of metastases. B7-H3 is an important immune checkpoint member of the B7 family and inhibits T-cell mediated antitumor immunity. Its expression is associated with a negative prognosis and a poor clinical outcome. Based on the clinical success of inhibitory immune checkpoint blockade, monoclonal antibodies (mAbs) against B7-H3 appear to be a promising therapeutic strategy. The proliferation biomarker, Ki-67, is used as a prognostic factor for breast cancer and reflects the proliferative potential of the tumor. In order to better understand the role of B7-H3 and Ki-67 in cancer development, in this study, we used a real-time biopsy for determining both biomarkers on CETCs in breast cancer patients. Blood from 50 patients suffering from breast cancer was analyzed for CETCs and the expression of B7-H3 and Ki-67 using the maintrac® method. B7-H3 expression on CETCs was found in 82% of the patients. The frequency of B7-H3- and Ki-67‑positive CETCs was significantly higher in patients who had received radiation therapy compared to patients who had not received irradiation. B7-H3‑positive CETCs seemed to be more aggressive as the percentage of B7-H3‑positive CETCs correlated with the percentage of cells positive for the proliferation marker, Ki-67 (r=0.72 P<0.001). A significant association between the Ki-67 and B7-H3 expression level on the CETCs and nodal status was observed. On the whole, the findings of this study indicate that breast cancer patients have detectable CETCs with a high frequency of B7-H3 expression regardless of the stage of the disease. B7-H3 seems to be an important factor in immune evasion and may thus be a promising target for anticancer therapies. Radiation may lead to an upregulation of B7-H3 expression on CETCs, which could be a possible mechanism of acquired radio-resistance.

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“…It is common practice to change mCRPC treatment if there are signs of progressive disease, and in EXTREQOL 54% of patients had switched to next line therapies. According to a recent survey of 118 prostate cancer specialists, most clinicians favour clinical progression over prostate-specific antigen or imaging to drive treatment switch decisions [28]. Another recent survey of 109 specialists showed that treatment decisions are also influenced by whether or not patients live alone.…”

Section: Discussionmentioning

confidence: 99%

Treatment Experiences, Information Needs, Pain and Quality of Life in Men with Metastatic Castrate-resistant Prostate Cancer: Results from the EXTREQOL Study

et al. 2019

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Delaying progression, ameliorating symptoms and maintaining Quality of Life (QoL) are primary aims of treatment for metastatic Castrate Resistant Prostate Cancer (mCRPC). Real world rather than clinical trial data about symptoms and side effects are sparse. In EXTREQOL patients' QoL, pain and information needs were recorded during treatment. Methods Men with mCRPC from 20 UK cancer centres commencing various systemic mCRPC treatments completed QoL, pain and information needs questionnaires at baseline, 3 and 6 months. Results 132 patients were recruited. Overall QoL declined significantly by 6 months (Functional Assessment of Cancer Therapy-Prostate (FACT-P) mean=-3.89, 95% CI:-6.7 to-1.05, p =0.007; Trial Outcome Index analysis (TOI) mean=-3.10, 95% CI:-5.34 to-0.83, p = 0.007. Those who came off novel therapy and remained on LHRH agonist therapy alone had worse scores than patients receiving concomitant chemotherapy (Prostate Concerns Subscale (PSC) mean difference=-4.45, 95% CI: 95%

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Interrogating Metastatic Prostate Cancer Treatment Switch Decisions: A Multi-institutional Survey

Cited by 19 publications

References 31 publications

Circulating tumor cells, tumor-derived extracellular vesicles and plasma cytokeratins in castration-resistant prostate cancer patients

Circulating tumor cells, tumor-derived extracellular vesicles and plasma cytokeratins in castration-resistant prostate cancer patients

B7-H3 on circulating epithelial tumor cells correlates with the proliferation marker, Ki-67, and may be associated with the aggressiveness of tumors in breast cancer patients

Treatment Experiences, Information Needs, Pain and Quality of Life in Men with Metastatic Castrate-resistant Prostate Cancer: Results from the EXTREQOL Study

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