Japanese Journal of Clinical Oncology 32:118-119 (2002)
© 2002 Foundation for Promotion of Cancer Research
Editorial |
Cancer Screening in Patients with Cancer
National Cancer Center Hospital, Tokyo, Japan
Interest in multiple primary malignant neoplasms is long-standing since the Warren–Gates report (1) in 1932. We have the impression that multiple cancer cases have recently been increasing in number. Multiple primary neoplasms in the same individual are experienced more frequently as advances in cancer treatment prolong life. Improved survival rates for patients with neoplastic disease, largely due to early diagnosis, allow more patients to survive long enough to develop subsequent primary tumors.
The development of more sophisticated invasive and non-invasive diagnostic tools has made it possible to detect cancer at an early stage. Furthermore, it has contributed to the detection of synchronous occult tumors which were formerly overlooked. Cases of multiple primary cancers raise questions about underlying environmental factors or host susceptibility factors. A true increase in the occurrence of additional carcinoma from an unknown cause is strongly suspected.
Environmental factors are thought to play a major role in carcinogenesis. Carcinogens have a regional carcinogenic effect over an area in which multiple cell groups undergo a process toward malignancy. In individuals developing multiple primary malignancies in functionally and anatomically allied organs, environmental factors are thought to play a major role in carcinogenesis. Carcinogenesis in different organs subjected to the same carcinogens and promoting factors has led to the concept of a multicentric pathogenic process termed ‘field cancerization’ (2). In patients with multiple primary cancers, intercancer correlations were found to be statistically significant.
An individual developing more than one primary tumor in anatomically and functionally unrelated organs may be considered ‘cancer-prone.’ Genetic cancer susceptibility is acquired when cancer-predisposing mutations occur. People with a family history of cancer will inherit genetic cancer susceptibility as a risk factor for cancer. Gene mutations influence cancer susceptibility through changes of metabolism and catabolism of carcinogens. Tumor suppressor genes, such as p53 and FHIT, may be candidates for target genes of these risk factors (3). Genetic instability is also considered a driving force behind carcinogenesis and the alterations of the length of single repetitive genomic sequences or microsatellite instability, implicating impaired DNA repair mechanism (4). Genetic background may influence the development of multiple primary tumors. Newly diagnosed people and survivors of earlier cancers, who have genetic cancer susceptibility, therefore, have an increased risk of multiple primary tumors.
The incidence of multiple primary cancers in patients with esophageal cancer is known to be high. Subsequent other primary cancers have become a new problem for patients who survive esophageal cancer. Squamous cell carcinoma of the esophagus is associated with cancers of the upper respiratory and digestive tract. Although the reason for the high frequency of additional malignancies in esophageal cancer patients is yet to be identified, the most convincing hypothesis is the field cancerization theory. Carcinogens affecting the esophagus also affect the entire respiratory and upper digestive tracts. Alcohol and tobacco consumption are the most common risk factors in patients with esophageal carcinoma. These are also known as crucial environmental risk factors for multiple cancers of the upper aero-digestive tract. Subsequent cancers of the stomach and hypopharynx develop significantly more frequently in heavy smokers (5). Oncoprotein overexpression or gene amplification is also associated with almost all gastrointestinal tract malignancies including esophageal, gastric and colorectal cancers (6).
In this issue, Kagei et al. (7) report the high incidence and relatively good outcome for patients with second primary carcinoma to justify the efficacy of screening for multiple primary cancers in patients with esophageal cancer. Patients with esophageal cancer are especially at high risk of developing squamous cell carcinoma in the head and neck. Panendoscopy is recommended on all patients with a carcinoma of the aero-digestive tract to diagnose simultaneous or synchronous primary tumors based on the field cancerization theory (8). Among carcinomas of the aero-digestive tract, esophageal squamous cell carcinoma and gastric cancer are rarely associated except in Japan. An association with adenocarcinomas of the stomach may be coincidental owing to the high frequency of gastric and esophageal tumors in Japan (9). Esophageal squamous cell carcinoma and lung cancer also appear to be rarely associated (10). The prospective study could not distinguish the patients at high risk of developing esophageal and co-existing colorectal cancer (11).
Kagei et al. reported the efficacy of screening and surveillance for synchronous second primary cancer in patients with esophageal cancer (7). The efficacy of screening should be estimated in terms of cost–benefit. For improving cost–benefit, it is important to define the appropriateness of particular surveillance approaches and identify a subject with an increased risk of cancer. The significance of the high detection rates of synchronous second primary cancer should be evaluated using the observed-to-expected ratio (O/E ratio) (12). The patterns of occurrence of additional cancers may be coincidental and the frequency of occurrence largely determined by the age, gender, year or nation of the patient. To obtain the expected number of additional primary carcinomas by site, we should calculate the person-year for each patient and apply the person-years to the site-, age-, gender- and year-specific cancer incidence tables for the nation and total the resulting numbers for all the patients. In Kagei et al.’s paper, however, their study was not evaluated with correction for age, gender or calendar year.
In general, patients who have a cancer are considered to have underlying environmental factors or host susceptibility factors for neoplasms. They might be at high risk of developing other tumors. The frequency of occurrence of malignancy is largely determined by the age of the patient. Also, a positive correlation of a high degree was confirmed between the male and female cancer risks in cancer sites including the esophagus, stomach, colon, rectum and lung (13). Patients with esophageal carcinoma are mostly elderly men with smoking and drinking behaviors. They are a high-risk group for cancer of the upper aero-digestive tract with age, gender, environmental factors and host susceptibility. They are the most selected candidates for screening programs for cancer.
For screening and surveillance for synchronous second primary cancer, Kagei et al. applied procedures including endoscopy and CT scanning (7). These techniques are already indispensable for histological diagnosis and accurate staging at the time of initiating treatment for esophageal cancer. During esophagogastroscopy, the stomach is inspected for availability for reconstruction after esophagectomy and detection of coincident occult gastric tumor. The major role of CT scanning in staging of esophageal cancer is to identify lung and liver metastasis. Furthermore, it plays a useful role for screening for second primary tumors in the lung and liver.
According to recent reports (14), staging accuracy in esophageal cancer was improved by positron emission tomography (PET). PET is useful in identifying sites of distant metastasis missed by conventional scanning including CT, EUS and bone scan. Some reports have appeared on the detection of occult metastatic disease and primary coincident malignancy (15). This imaging may reveal clinically occult second lesions. With the introduction of PET as a means of staging of cancer, clinically occult coincident primary tumors at initial presentation may be expected to increase. PET has the potential to change oncological examination for screening and surveillance for occult primary cancers for subjects with or even without a primary carcinoma.
REFERENCES
1 Warren S, Gates O. Multiple primary malignant tumors. A survey of the literature and a statistical study. Am J Cancer 1932;16:1358–414.
2 Slaughter DP, Southwick HW, Smejkal W. Field cancerization in oral stratified squamous epithelium. Clinical implications of multicentric origin. Cancer 1953;6:963–8.[Web of Science][Medline]
3 Morita M, Saeki H, Mori M, Kuwano H, Sugimachi K. Risk factors for esophageal cancer and the multiple occurrence of carcinoma in the upper aerodigestive tract. Surgery 2002;131(1 Suppl):S1–S6.[Medline]
4 Sardi I, Franchi A, Bocciolini C, Mechi C, Frittelli A, Bruschini L, et al. Microsatellite instability as biomarker for risk of multiple primary malignancies of the upper aerodigestive tract. Oncol Rep 2001;8:393–9.[Medline]
5 Kokawa A, Yamaguchi H, Tachimori Y, Kato H, Watanabe H, Nakanishi Y. Other primary cancers occurring after treatment of superficial oesophageal cancer. Br J Surg 2001;88:439–43.[Medline]
6 Ross JS, McKenna BJ. The HER-2/neu oncogene in tumors of the gastrointestinal tract. Cancer Invest 2001;19:554–68.[Web of Science][Medline]
7
Kagei K, Hosokawa M, Shirato H, Kusumi T, Shimizu Y, Watanabe A, et al. Efficacy of intense screening and treatment for synchronous second primary cancers in patients with esophageal cancer. Jpn J Clin Oncol 2002;32:120–27.
8 Makuuchi H, Machimura T, Shimada H, Mizutani K, Chino O, Kise Y, et al. Endoscopic screening for esophageal cancer in 788 patients with head and neck cancers. Tokai J Exp Clin Med 1996;21:139–45.[Medline]
9 Kumagai Y, Kawano T, Nakajima Y, Nagai K, Inoue H, Nara S, et al. Multiple primary cancers associated with esophageal carcinoma. Surg Today 2001;31:872–6.[Medline]
10 Fekete F, Sauvanet A, Kaisserian G, Jauffret B, Zouari K, Berthoux L, et al. Associated primary esophageal and lung carcinoma: a study of 39 patients. Ann Thorac Surg 1994;58:837–42.[Abstract]
11 Kuwano H, Nozoe T, Sumiyoshi K, Yasuda M, Watanabe M, Ohno S, et al. Oesophageal cancer coexisting with colorectal lesions. Eur J Surg 1996;162:797–800.[Medline]
12 Saikawa M, Ebihara S, Yoshizumi T, Ohyama W. Multiple primary cancers in patients with squamous cell carcinoma of the oral cavity. Jpn J Cancer Res 1991;82:40–5.[Web of Science][Medline]
13 Kodama M, Kodama T. The interference of geographical changes of cancer risk in tumor etiology in Japan. Anticancer Res 1993;13:1035–42.[Medline]
14
Flamen P, Lerut A, Van Cutsem E, De Wever W, Peeters M, Stroobants S, et al. Utility of positron emission tomography for the staging of patients with potentially operable esophageal carcinoma. J Clin Oncol 2000;18:3202–10.
15 Stokkel MP, de Klerk JM, Hordijk GJ. Fluorodeoxyglucose positron emission tomography, a new technique for increasing the detection rate of coincident thyroid cancer in head and neck oncology. Eur Arch Otorhinolaryngol 2000;257:552–4.[Medline]
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||