The efficacy of a serum carboxyterminal pyridinoline cross-linked telopeptide of type I collagen as a quantitative screening marker for bone metastases in patients with urological malignancies

doi:10.1016/S0361-090X(02)00172-1

Cancer Detection and Prevention

Volume 27, Issue 1, 2003, Pages 14-18

https://doi.org/10.1016/S0361-090X(02)00172-1 Get rights and content

Abstract

In order to ascertain whether carboxyterminal pyridinoline cross-linked telopeptide of type I collagen (ICTP) might be useful as a serum screening parameter for bone metastases from non-prostate urological malignancies as well as prostate cancers, as series of 210 patients were examined. In addition to ICTP, serum alkaline phosphatase (ALP) and also prostate specific antigen (PSA) in the prostate cancer cases were assayed using commercial kits. The areas under the receiver operating characteristic (ROC) curves were 0.7846 for ICTP (cut-off point 9.6 μg/l), 0.8304 for ALP in prostate cancer cases, and 0.8278 for ICTP (cut-off point 10.6 μg/l), and 0.7139 for ALP in non-prostate cancer cases. While significance was only observed for ICTP and PSA in prostate cancer cases, borderline significance was also evident with ICTP for non-prostate malignancies, and with ALP for prostate cancer case. The results suggest that serum ICTP may be useful in combination with ALP as a quantitative clinical marker for low cost screening for bone metastases in patients with all types of urological malignancies.

Introduction

Bone metastasis is a frequent event with various malignancies and is a significant clinical problem in advanced cases, associated with pain and pathological bone fractures. In the urological field, prostate cancer is well known to metastasize selectively to bone, but this site may also be frequently involved with other urological malignancies. Therefore, detecting and monitoring bone metastases are very important regarding treatment of these cancers.

Bone scintigraphy combined with magnetic resonance imaging (MRI) is considered to be the most sensitive and non-invasive technique for detection of bone metastasis. However, these imaging techniques are both quite expensive, and are not accurate for comparison purposes. Moreover, bone scintigraphy detects not only active metastatic lesions, but also healing processes after treatment of bone metastases.

In contrast, blood sampling for analysis of serum markers is very simple and well tolerated for repeated checks. ALP activity, osteocalcin, and many kinds of markers of bone metastases in blood have therefore been employed, but none has so far proven to be really clinically useful [1], [2], [3].

Bone metastasis is quite different from other metastases regarding its unique pattern of development, which consists of multiple and complex sequential steps, as noted by Yoneda in his description of mechanisms of cellular and molecular bone metastasis from breast and prostate cancers [4]. Clearly, if some specific substance involved in bone metabolism demonstrate altered levels, it should be possible to apply this for early detection and assess early treatment effects.

Telopeptide of type I collagen (ICTP) has for several years been widely used for detecting bone metastases in lung and breast cancer cases [5], [6], [7], and is also well recognized to have utility for prostatic cancers [8], [9], [10]. It is documented to be a serum marker of bone collagen degradation [11], [12], [13]. However, there have been almost no reports on ICTP regarding urothelial or kidney cancers which are relatively commonly associated with bone metastasis. Therefore, we compared clinical results for bone metastasis and serum concentrations of ICTP in patients with such urological malignancies.

Section snippets

Patients and methods

From April 1999 to July 2000, we experienced a total of 210 cases of histopathologically proven urological malignancies (prostatic cancer: 119 cases; urothelial cancer: 68 cases; kidney cancer: 23 cases) in Nagoya City University and affiliated hospitals. Of the 119 prostatic cancer patients, 9 were untreated, and the remainder under-went radical prostatectomy, hormone therapy, radiation therapy, or a combination of these treatments. Of the 68 urothelial cancers, 9 were untreated, and the rest

Results

The overall results for prostate and non-prostate cancers are summarized in Fig. 1. In both cases, significant elevation was evident in ICTP values for cases with metastases. Similar results were obtained with ALP and PSA for prostate, and with one exception, ALP with other urothelial malignancies. Because of the relatively small numbers, urothelial and kidney cancers were combined as one non-prostate cancer group.

In prostate cancer patients, the areas under the ROC curves and corresponding

Discussion

The results of the present study indicate that serum ICTP may have superior or equal efficacy to ALP for prediction of bone metastases from prostate and urothelial malignancies. It has been well documented that ICTP is useful for this purpose with prostate cancer cases (Kylmälä et al. [8]). In fact, it was earlier also proposed as a serum marker for multiple myeloma (Elomaa et al. [16]) and bone collagen degradation (Risteli et al. [13]).

Regarding the statistical treatment of our results, it is

Acknowledgements

We wish to thank Mr. Yoshikazu Nakao, Chugai Diagnostics Science Co. Ltd. for statistical analyses, and Dr. Malcolm Moore for reviewing the English language of our manuscript.

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The efficacy of a serum carboxyterminal pyridinoline cross-linked telopeptide of type I collagen as a quantitative screening marker for bone metastases in patients with urological malignancies

Abstract

Introduction

Section snippets

Patients and methods

Results

Discussion

Acknowledgements

Eur. J. Cancer

Eur. J. Cancer

J. Urol.

Bone alkaline phosphatase isoenzyme and urinary hydroxyproline in healthy subjects, patients with osteolytic metastasis, and patients with primary hyperparathyroidism

Neoplasia

Biochemical prediction of response of bone metastases to treatment

Br. J. Cancer

Assay of urinary pyridinoline and deoxypyridinoline as potential markers of the rate bone resorption: usefulness of urinary pyridinoline and deoxypyridinoline in patients with prostate cancer with bone metastasis

Jpn. J. Urol.

Serum concentrations of type I collagen carboxyterminal telopeptide (ICTP) and type I procollagen carboxy- and aminoterminal propeptides (PIPC, PINP) as markers of metastatic bone disease in breast cancer

Anticancer Res.

Bone metabolic markers in bone metastasis of breast cancer

Int. J. Clin. Oncol.

Usefulness of serum carboxy-terminal telopeptide of type I collagen (ICTP) as a marker of bone metastasis from lung cancer

Jpn. J. Clin. Oncol.