Serum Biomarkers of Bone Metabolism in Castration-Resistant Prostate Cancer Patients With Skeletal Metastases: Results From SWOG 0421

Lara, Primo N.; Ely, Benjamin; Quinn, David I.; Mack, Philip C.; Tangen, Catherine M.; Gertz, Erik; Twardowski, Przemyslaw; Goldkorn, Amir; Hussain, Maha; Vogelzang, Nicholas J.; Thompson, Ian M.; Loan, Marta D. Van

doi:10.1093/jnci/dju013

Cited by 49 publications

(41 citation statements)

References 25 publications

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“…These include serum androgens . serum biomarkers based on quantitative analysis of the phosphatase and tensin homolog conditional knockout mouse proteome, serum biomarkers of bone metabolism, molecular markers in key steroidogenic pathways, and circulating tumors cells . The utility of inflammation‐based markers in prostate cancer also appears valid in this setting.…”

Section: Discussionmentioning

confidence: 99%

Simple prognostic score for metastatic castration‐resistant prostate cancer with incorporation of neutrophil‐to‐lymphocyte ratio

Templeton

Pezaro

Omlin

et al. 2014

Cancer

128

106

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BACKGROUND:The neutrophil-to-lymphocyte ratio (NLR), a marker of inflammation, has been reported to be a poor prognostic indicator in prostate cancer. Here we explore the use of the NLR to establish a simple prognostic score for men with metastatic castration-resistant prostate cancer (mCRPC) treated with docetaxel. METHODS: In the training cohort, the NLR and other known prognostic variables were evaluated among a cohort of chemotherapy-na€ ıve patients treated with thrice-weekly docetaxel at the Princess Margaret Cancer Centre. Significant prognostic variables identified by univariable Cox regression were evaluated by the area under the receiver operating characteristic curves. Multivariable Cox regression was then used to derive a prognostic score where 1 risk point was assigned for each significant variable. The model was externally validated in a cohort of patients treated at the Royal Marsden. RESULTS: Three hudred fifty-seven patients were analyzed in the training cohort. Median age was 71 years, 12% had liver metastasis, and median overall survival (OS) was 14.7 months. Liver metastases, hemoglobin <12 g/dL, alkaline phosphatase >2.03 upper limit of normal (ULN), lactate dehydrogenase >1.23 ULN, and NLR >3 were associated with significantly worse OS in multivariable analysis. Four risk categories were subsequently established with 0, 1, 2, and 3-5 points. Two-year OS rates for these categories were 43%, 37%, 12%, and 3%, respectively. Area under the curve for the training cohort was 0.78 (95% CI, 0.72-0.84) compared with 0.66 (95% CI, 0.58-0.74) for the 215 patients in the validation cohort. CONCLUSIONS: This simple risk score provides good prognostic and discriminatory accuracy for men with mCRPC. Cancer 2014;120:3346-53.

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Section: Discussionmentioning

confidence: 99%

Simple prognostic score for metastatic castration‐resistant prostate cancer with incorporation of neutrophil‐to‐lymphocyte ratio

Templeton

Pezaro

Omlin

et al. 2014

Cancer

128

106

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“…The authors evaluated two “bone formation” (BALP, P1CP) and two “bone resorption” (NTX, PYD) markers, both at baseline and at regular intervals, describing a correlation between worse survival and the evidence of high baseline levels and/or progressive increase of each marker (p < .001). The trial did not meet its primary endpoint, but the patients with the highest BTM concentration (upper 25th percentile) benefited from atrasentan in terms of median survival (13 months vs 5 months with placebo; p = .005) [50] .…”

Section: Methodsmentioning

confidence: 96%

The role of biomarkers in the management of bone-homing malignancies

D’Oronzo

Brown

Coleman

2017

Journal of Bone Oncology

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Bone represents a common site of metastasis from several solid tumours, including breast, prostate and lung malignancies. The onset of bone metastases (BM) is associated not only with serious skeletal complications, but also shortened overall survival, owing to the lack of curative treatment options for late-stage cancer.Despite the diagnostic advances, BM detection often occurs in the symptomatic stage, underlining the need for novel strategies aimed at the early identification of high-risk patients. To this purpose, both bone turnover and tumour-derived markers are being investigated for their potential diagnostic, prognostic and predictive roles.In this review, we summarize the pathogenesis of BM in breast, prostate and lung tumours, while exploring the current research focused on the identification and clinical validation of BM biomarkers.

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“…Biochemical markers of bone resorption (serum C-terminal telopeptide [CTX], urinary N-terminal telopeptide [NTX] and others) and bone formation (bone-specific alkaline phosphatase [BSAP], serum N-terminal propeptide of type 1 collagen [PINP] and others) have been proposed for the diagnosis, prognosis and monitoring of bone metastases 106,107 . Their role in routine practice has yet to be defined with certainty, but a study evaluating the role of bone markers in the future selection of patients who might benefit from certain specific therapies is ongoing 108 . In addition, cross-sectional imaging techniques (CT or MRI) are considered adequate modalities to measure lytic or mixed lesions with a soft tissue component 109 .…”

Section: Managing Skeletal Complications Of Cancermentioning

confidence: 99%

The best of both worlds — managing the cancer, saving the bone

et al. 2015

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In the context of breast cancer, the importance of the skeleton in the regulation of primary tumour development and as a site for subsequent metastasis is well characterized. Our understanding of the contributions made by the host bone and bone marrow cells increasingly demonstrates the extent of the interaction between tumour cells and normal host cells. As a result, the need to develop and utilize therapies that can impede the growth and/or function of tumour cells while sparing normal host bone and bone marrow cells is immense and expanding. The need for these new treatments is, however, superimposed on the orthopaedic management of patients’ quality of life, where pain control and continued locomotion are paramount. Indeed, the majority of the anticancer therapies used to date often result in direct or indirect damage to bone. Thus, although the bone microenvironment regulates tumour cell growth in bone, cells within the bone marrow niche also mediate many of the orthopaedic consequences of tumour progression as well as resistance to the antitumour effects of existing therapies. In this Review, we highlight the effects of existing cancer treatments on bone and the bone marrow microenvironment as well as the mechanisms mediating these effects and the current utility of modern orthopaedic interventions.

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Serum Biomarkers of Bone Metabolism in Castration-Resistant Prostate Cancer Patients With Skeletal Metastases: Results From SWOG 0421

Abstract: Serum bone metabolism markers have statistically significant independent prognostic value in CRPC. Importantly, a small group of patients (6%) with highly elevated markers of bone turnover appear to preferentially benefit from atrasentan therapy.

Cited by 49 publications

References 25 publications

Simple prognostic score for metastatic castration‐resistant prostate cancer with incorporation of neutrophil‐to‐lymphocyte ratio

Simple prognostic score for metastatic castration‐resistant prostate cancer with incorporation of neutrophil‐to‐lymphocyte ratio

The role of biomarkers in the management of bone-homing malignancies

The best of both worlds — managing the cancer, saving the bone

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