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Discovery and validation of a serum microRNA signature to characterize oligo- and polymetastatic prostate cancer : not ready for prime time

Bert Dhondt (UGent) , Elise De Bleser (UGent) , Tom Claeys, Sarah Buelens (UGent) , Nicolaas Lumen (UGent) , Jo Vandesompele (UGent) , Anneleen Beckers, Valerie Fonteyne (UGent) , Kim Van der Eecken (UGent) , Aurélie De Bruycker (UGent) , et al.
(2019) WORLD JOURNAL OF UROLOGY. 37(12). p.2557-2564
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Abstract
Purpose Patients with oligometastatic prostate cancer (PC) may benefit from metastasis-directed therapy (MDT), delaying disease progression and the start of palliative systemic treatment. However, a significant proportion of oligometastatic PC patients progress to polymetastatic PC within a year following MDT, suggesting an underestimation of the metastatic load by current staging modalities. Molecular markers could help to identify true oligometastatic patients eligible for MDT. Methods Patients with asymptomatic biochemical recurrence following primary PC treatment were classified as oligo- or polymetastatic based on 18(F)-choline PET/CT imaging. Oligometastatic patients had up to three metastases at baseline and did not progress to more than three lesions following MDT or surveillance within 1 year of diagnosis of metastases. Polymetastatic patients had > 3 metastases at baseline or developed > 3 metastases within 1 year following imaging. A model aiming to prospectively distinguish oligo- and polymetastatic PC patients was trained using clinicopathological parameters and serum-derived microRNA expression profiles from a discovery cohort of 20 oligometastatic and 20 polymetastatic PC patients. To confirm the models predictive performance, it was applied on biomarker data obtained from an independent validation cohort of 44 patients with oligometastatic and 39 patients with polymetastatic disease. Results Oligometastatic PC patients had a more favorable prognosis compared to polymetastatic ones, as defined by a significantly longer median CRPC-free survival (not reached versus 38 months; 95% confidence interval 31-45 months with P < 0.001). Despite the good performance of a predictive model trained on the discovery cohort, with an AUC of 0.833 (0.693-0.973; 95% CI) and a sensitivity of 0.894 (0.714-1.000; 95% CI) for oligometastatic disease, none of the miRNA targets were found to be differentially expressed between oligo- and polymetastatic PC patients in the signature validation cohort. The multivariate model had an AUC of 0.393 (0.534 after cross-validation) and therefore, no predictive ability. Conclusions Although PC patients with oligometastatic disease had a more favorable prognosis, no serum-derived biomarkers allowing for prospective discrimination of oligo- and polymetastatic prostate cancer patients could be identified.
Keywords
Urology, Prostate cancer, Oligometastasis, miRNA, Serum, Biomarker, Machine learning, METASTASIS-DIRECTED THERAPY, RECURRENCE, SURVIVAL

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MLA
Dhondt, Bert, et al. “Discovery and Validation of a Serum MicroRNA Signature to Characterize Oligo- and Polymetastatic Prostate Cancer : Not Ready for Prime Time.” WORLD JOURNAL OF UROLOGY, vol. 37, no. 12, 2019, pp. 2557–64, doi:10.1007/s00345-018-2609-8.
APA
Dhondt, B., De Bleser, E., Claeys, T., Buelens, S., Lumen, N., Vandesompele, J., … Ost, P. (2019). Discovery and validation of a serum microRNA signature to characterize oligo- and polymetastatic prostate cancer : not ready for prime time. WORLD JOURNAL OF UROLOGY, 37(12), 2557–2564. https://doi.org/10.1007/s00345-018-2609-8
Chicago author-date
Dhondt, Bert, Elise De Bleser, Tom Claeys, Sarah Buelens, Nicolaas Lumen, Jo Vandesompele, Anneleen Beckers, et al. 2019. “Discovery and Validation of a Serum MicroRNA Signature to Characterize Oligo- and Polymetastatic Prostate Cancer : Not Ready for Prime Time.” WORLD JOURNAL OF UROLOGY 37 (12): 2557–64. https://doi.org/10.1007/s00345-018-2609-8.
Chicago author-date (all authors)
Dhondt, Bert, Elise De Bleser, Tom Claeys, Sarah Buelens, Nicolaas Lumen, Jo Vandesompele, Anneleen Beckers, Valerie Fonteyne, Kim Van der Eecken, Aurélie De Bruycker, Jérôme Paul, Pierre Gramme, and Piet Ost. 2019. “Discovery and Validation of a Serum MicroRNA Signature to Characterize Oligo- and Polymetastatic Prostate Cancer : Not Ready for Prime Time.” WORLD JOURNAL OF UROLOGY 37 (12): 2557–2564. doi:10.1007/s00345-018-2609-8.
Vancouver
1.
Dhondt B, De Bleser E, Claeys T, Buelens S, Lumen N, Vandesompele J, et al. Discovery and validation of a serum microRNA signature to characterize oligo- and polymetastatic prostate cancer : not ready for prime time. WORLD JOURNAL OF UROLOGY. 2019;37(12):2557–64.
IEEE
[1]
B. Dhondt et al., “Discovery and validation of a serum microRNA signature to characterize oligo- and polymetastatic prostate cancer : not ready for prime time,” WORLD JOURNAL OF UROLOGY, vol. 37, no. 12, pp. 2557–2564, 2019.
@article{8586484,
  abstract     = {Purpose Patients with oligometastatic prostate cancer (PC) may benefit from metastasis-directed therapy (MDT), delaying disease progression and the start of palliative systemic treatment. However, a significant proportion of oligometastatic PC patients progress to polymetastatic PC within a year following MDT, suggesting an underestimation of the metastatic load by current staging modalities. Molecular markers could help to identify true oligometastatic patients eligible for MDT.
Methods Patients with asymptomatic biochemical recurrence following primary PC treatment were classified as oligo- or polymetastatic based on 18(F)-choline PET/CT imaging. Oligometastatic patients had up to three metastases at baseline and did not progress to more than three lesions following MDT or surveillance within 1 year of diagnosis of metastases. Polymetastatic patients had > 3 metastases at baseline or developed > 3 metastases within 1 year following imaging. A model aiming to prospectively distinguish oligo- and polymetastatic PC patients was trained using clinicopathological parameters and serum-derived microRNA expression profiles from a discovery cohort of 20 oligometastatic and 20 polymetastatic PC patients. To confirm the models predictive performance, it was applied on biomarker data obtained from an independent validation cohort of 44 patients with oligometastatic and 39 patients with polymetastatic disease.
Results Oligometastatic PC patients had a more favorable prognosis compared to polymetastatic ones, as defined by a significantly longer median CRPC-free survival (not reached versus 38 months; 95% confidence interval 31-45 months with P < 0.001). Despite the good performance of a predictive model trained on the discovery cohort, with an AUC of 0.833 (0.693-0.973; 95% CI) and a sensitivity of 0.894 (0.714-1.000; 95% CI) for oligometastatic disease, none of the miRNA targets were found to be differentially expressed between oligo- and polymetastatic PC patients in the signature validation cohort. The multivariate model had an AUC of 0.393 (0.534 after cross-validation) and therefore, no predictive ability.
Conclusions Although PC patients with oligometastatic disease had a more favorable prognosis, no serum-derived biomarkers allowing for prospective discrimination of oligo- and polymetastatic prostate cancer patients could be identified.},
  author       = {Dhondt, Bert and De Bleser, Elise and Claeys, Tom and Buelens, Sarah and Lumen, Nicolaas and Vandesompele, Jo and Beckers, Anneleen and Fonteyne, Valerie and Van der Eecken, Kim and De Bruycker, Aurélie and Paul, Jérôme and Gramme, Pierre and Ost, Piet},
  issn         = {0724-4983},
  journal      = {WORLD JOURNAL OF UROLOGY},
  keywords     = {Urology,Prostate cancer,Oligometastasis,miRNA,Serum,Biomarker,Machine learning,METASTASIS-DIRECTED THERAPY,RECURRENCE,SURVIVAL},
  language     = {eng},
  number       = {12},
  pages        = {2557--2564},
  title        = {Discovery and validation of a serum microRNA signature to characterize oligo- and polymetastatic prostate cancer : not ready for prime time},
  url          = {http://dx.doi.org/10.1007/s00345-018-2609-8},
  volume       = {37},
  year         = {2019},
}

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