Utility of serum tumor markers during ... - Wiley Online Library

Original Article

Utility of Serum Tumor Markers During Surveillance for Stage I Seminoma Danny Vesprini, MD1,2,10; Peter Chung, MD2,10; Shaun Tolan, MD2,10; Mary Gospodarowicz, MD2,10; Michael Jewett, MD4,10; Martin O’Malley, MD5,10; Joan Sweet, MD6,10; Malcolm Moore, MD7,10; Tony Panzarella, MSc8,10; Jeremy Sturgeon, MD9; Linda Sugar, MD3; Lynn Anson-Cartwright, BSc2; and Padraig Warde, MD2,10

BACKGROUND: The serum tumor markers a-fetoprotein (AFP), b-human chorionic gonadotropin (HCG), and lactate dehydrogenase (LDH) are often measured as part of surveillance protocols in patients with stage I seminoma. In this study, the authors evaluated the utility of routine measurement of these markers in the detection of disease relapse. METHODS: Data were gathered from a prospectively maintained database of patients who underwent surveillance for stage I testicular seminoma diagnosed between 1982 and 2005 at Princess Margaret Hospital. Patients were followed on a predefined schedule with physical examination (PE), serum tumor markers, abdominopelvic computed tomography, and chest x-rays. The records of patients who relapsed were examined for details of imaging and serum tumor markers throughout the period of follow-up until the time of relapse. RESULTS: Of the 527 patients who were managed by surveillance, 75 patients (14%) relapsed at a median follow-up of 72 months. Of these, 65 patients relapsed within the first 3 years and had routine serum tumor markers measured. In total, 11 patients had abnormal tumor markers at the time of relapse (AFP, 0 patients; HCG, 6 patients; LDH, 4 patients; and HCG and LDH, 1 patient). Only 1 patient had an elevated tumor marker (LDH) before relapse, as defined by an abnormal imaging study (n ¼ 64) or physical examination (n ¼ 1), for which the treatment and outcome were not affected. CONCLUSIONS: Serum tumor marker levels did not aid in the early diagnosis of disease relapse in patients with stage I seminoma who were managed with surveillance. The current results indicated that routine measurement of C 2012 American serum tumor markers can be discontinued safely in seminoma surveillance schedules. Cancer 2012;118:5245-50. V Cancer Society. KEYWORDS: serum tumor markers, stage I seminoma, surveillance, biomarkers, relapse.

INTRODUCTION Surveillance is the management option of choice in patients with stage I seminoma.1-3 Although surveillance schedules may differ, most patients are followed with chest x-rays (CXR), computed tomography (CT) scans of the abdomen and pelvis (CT-AP), and measurement of the serum tumor markers a-fetoprotein (AFP), b-human chorionic gonadotropin (HCG), and lactate dehydrogenase (LDH).4,5 It has been demonstrated that knowledge of serum tumor markers levels is useful in the diagnosis and prognostication of germ cell tumors (GCTs),1,6 and studies have examined the role of tumor markers in detecting GCT relapse in patients with nonseminomatous GCTs (NSGCTs) or in heterogeneous populations of patients with GCTs.5,7-9 However, it is unclear whether routine measurement during surveillance in patients with stage I seminoma has any value in the early detection of relapse in addition to regular imaging studies.10,11 The focus of more recent work has been to optimize follow-up schedules to minimize the ‘‘burden’’ that men face after a diagnosis of stage I seminoma.5,11 However, the optimal surveillance schedule has not been established. Thus, as a part of this optimization process, we recently published a report on the lack of utility of CXR in seminoma surveillance.11 In the current study, we continue this work and examine the role of routine measurement of serum tumor markers in the identification of relapse in patients with stage I seminoma who undergo surveillance. MATERIALS AND METHODS Data were gathered from a prospectively maintained institutional database after we obtained local research ethics board approval. The medical records of all patients with histologically confirmed, stage I testicular seminoma who were managed with surveillance between 1982 and 2005 were examined to allow for a minimum of 3 years of follow-up. Patients initially Corresponding author: Peter Chung, MD, University of Toronto, Department of Radiation Oncology, Radiation Medicine Program, Princess Margaret Hospital, University Health Network, 5th Floor, 610 University Avenue, Toronto, Ontario, M5G 2M9 Canada; Fax: (416) 946-2111; [email protected] 1 Department of Radiation Oncology, Sunnybrook Odette Cancer Center, Toronto, Ontario, Canada; 2Department of Radiation Oncology, Princess Margaret Hospital, University Health Network, Toronto, Ontario, Canada; 3Department of Pathology, Sunnybrook Health Sciences Center, Toronto, Ontario, Canada; 4Department of Urology, Princess Margaret Hospital, Toronto, Ontario, Canada; 5Department of Diagnostic Radiology, University of Toronto, Toronto, Ontario, Canada; 6Department of Pathology, Princess Margaret Hospital, University Health Network, Toronto, Ontario, Canada; 7Department of Medical Oncology, Princess Margaret Hospital, University Health Network, Toronto, Ontario, Canada; 8Department of Biostatistics, Princess Margaret Hospital, University Health Network, Toronto, Ontario, Canada; 9Department of Medical Oncology, McGill University Health Center, Montreal, Quebec, Canada; 10University of Toronto, Toronto, Ontario, Canada

DOI: 10.1002/cncr.27539, Received: November 23, 2011; Revised: February 13, 2012; Accepted: February 21, 2012, Published online April 19, 2012 in Wiley Online Library (wileyonlinelibrary.com)

Cancer

November 1, 2012

5245

Original Article Table 1. Typical Surveillance Schedule for Patients With Stage I Seminoma at Princess Margaret Hospital During the Study Period

Month Year

1

2

3

4

5

6

7

8

9

10

11

12

1 2 3 4 5 6 7 8 9 10

— — — — — — — — — —

— — — — — — — — — —

— — — — — — — — — —

Markers, CT-AP Markers, CT-AP, CXR Markers, CT-AP — — — — — — —

— — — — — — — — — —

— — — CT-AP CT-AP CT-AP CT-AP — — —

— — — — — — — — — —

Markers, CT-AP, CXR Markers, CT-AP Markers, CT-AP — — — — — — —

— — — — — — — — — —

— — — — — — — — — —

— — — — — — — — — —

Markers, CT-AP Markers, CT-AP, CXR Markers, CT-AP, CXR CT-AP, CXR CT-AP, CXR CT-AP, CXR CT-AP, CXR CT-AP, CXR CT-AP, CXR CT-AP, CXR

Abbreviations: CT-AP, computed tomography scan of the abdomen and pelvis; CXR, chest radiograph; Markers, serum tumor markers.

Table 2. Abnormal Serum Tumor Markers in Patients Who Relapsed During the Stage I Seminoma Surveillance Protocol

Serum Tumor Marker Levels at Relapsea Patient

AFP, lg/L

HCG, IU/L

LDH, U/L

Site of Relapse

LN Size in Greatest Dimension, cmb

Time to Relapse From Diagnosis, mo

Treatment of Relapse

1c 2c 3c 4c 5c,d 6e 7e 8e 9e 10e 11e