How To Know If You Have Colorectal Cancer, Other Primary Cancer, Or Sporadic Cancer

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1 CLINICAL CHARACTERISTICS OF PATIENTS WITH SPORADIC COLORECTAL CANCER AND PRIMARY CANCERS OF OTHER ORGANS Jung-Yu Kan, 1 Jan-Sing Hsieh, 1,3 Yong-Sang Pan, 2,3 Wen-Ming Wang, 2,3 Fang-Ming Chen, 1,3 Chang-Ming Jan, 2,3 Yu-Sheng Huang, 1,3 Tsung-Jen Huang, 1,3 and Jaw-Yuan Wang 1,3 Departments of 1 Surgery and 2 Internal Medicine, Kaohsiung Medical University Hospital, and 3 Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. Most cancer patients often neglect the possibility of secondary cancer. Colorectal cancer (CRC) is the third leading cause of cancer death in Taiwan. It is important to be aware of the clinical characteristics of double cancer in CRC patients for early diagnosis and treatment. We retrospectively analyzed 1,031 CRC patients who underwent surgical treatment at the Department of Surgery of Kaohsiung Medical University Hospital between January 1998 and December Among these patients, CRC was accompanied by cancer of other organs in 17 patients (1.65%), either synchronously or metachronously. Therefore, we describe our experience regarding the location of CRC, the clinical symptoms and signs of these patients, the TNM stage, histology, phase, association with other malignancies, interval between cancers and clinical outcomes. Of the 17 patients in whom CRC was accompanied by primary cancer of other organs, there were four synchronous and 13 metachronous multiple cancer patients. Our patient group comprised six men and 11 women with ages ranging from 47 to 88 years (median age, 66 years). The most common location of CRC was the sigmoid colon. Six gastric cancers (35.2%) and six breast cancers (35.2%) were associated with primary CRC. The remaining six second primary cancers were one lung cancer, one thyroid cancer, one cervical cancer, one ovarian cancer, one skin cancer, and one urinary bladder cancer. Of the 13 metachronous multiple cancer patients, eight patients developed subsequent CRC after primary cancers of other organs, whereas two patients developed a subsequent second primary cancer after CRC. The intervals between the development of metachronous multiple cancers ranged from 2 to 19 years. In this retrospective analysis, breast and gastric cancer patients were at increased risk of developing subsequent secondary CRC. Careful attention should always be paid to the possibility of secondary CRC in treating these cancer patients. Cancer patients with hematochezia or gastrointestinal symptoms/signs should be evaluated for the possibility of second primary CRC during their regular follow-up. Key Words: colorectal cancer, other primary cancer, sporadic (Kaohsiung J Med Sci 2006;22:547 53) Colorectal cancer (CRC) is the second leading cause of cancer-related mortality in Europe and USA, and Received: May 26, 2006 Accepted: August 1, 2006 Address correspondence and reprint requests to: Dr Jaw-Yuan Wang, Department of Surgery, Kaohsiung Medical University Hospital, 100 Tzyou 1 st Road, Kaohsiung 807, Taiwan. cy614112@ms14.hinet.net approximately 300,000 new cases and 200,000 deaths due to CRC are reported in these areas annually [1]. CRC is also the third major cause of cancer-related death in Taiwan, with over 7,000 new cases and 3,000 deaths/year [2]. With the recent advent of improvements in prognosis, many CRC patients may survive for longer after treatment. However, these patients are expected to be at increased risk of Kaohsiung J Med Sci November 2006 Vol 22 No Elsevier. All rights reserved.

2 J.Y. Kan, J.S. Hsieh, Y.S. Pan, et al developing second other-site primary cancers, or they may redevelop CRC after primary cancer of other organs. Although synchronous and metachronous CRC are now well known to all colorectal surgeons, second other-site primary cancers accompanying CRC are unfamiliar to most colorectal physicians. Knowledge of the clinical characteristics of these second primary cancers becomes important especially during postoperative surveillance of these patients. In this article, we describe our clinical experience of CRC patients with other associated primary cancers, and review the literature. MATERIALS AND METHODS Between January 1998 and December 2004, 1,031 sporadic CRC patients underwent surgical treatment at the Department of Surgery of Kaohsiung Medical University Hospital. Among these patients, CRC was accompanied by cancer of other organs in 17 (1.65%), either synchronously or metachronously. The inclusion criteria were that each tumor had to have a definite histologic picture of malignancy, and clearly no origin of metastasis from another tumor. Second cancers detected within 1 year after the detection of the initial cancers were regarded as synchronous cancers. The medical records including patients demographics, clinical and pathologic features, operative details, and outcomes were retrospectively reviewed. Clinical stage and pathologic features of primary CRC were defined according to the criteria of the American Joint Commission on Cancer [3]. RESULTS Table 1 lists the demographics and clinical features of CRC patients with other primary cancers. There were four synchronous and 13 metachronous multiple cancer patients. The group comprised six men and 11 women with ages ranging from 47 to 88 years (median age, 66 years). The most common site of CRC was the sigmoid colon. Primary cancers of other organs were six breast cancers (35.2%) and six gastric cancers (35.2%). The remaining six cancers included one lung cancer, one thyroid cancer, one cervical cancer, one ovarian cancer, one skin cancer, and one urinary bladder cancer. One patient had triple primary cancers involving the stomach, breast, and colon. The intervals between the development of multiple primary cancers ranged from 2 to 19 years. The TNM stages of the CRC patients were as follows: five patients were stage I (29.4%), three patients were stage II (17.6%), seven patients were stage III (41.2%), and two patients were stage IV (11.8%). With regard to the histologic types of these tumors, six (35.3%) were well-differentiated carcinoma, eight (47.1 %) were moderately differentiated carcinoma, and three (17.6%) were poorly differentiated carcinoma. Of the 13 metachronous multiple cancer patients, 11 developed subsequent CRC after cancers of other organs, whereas two patients developed subsequent primary cancer after CRC. Most of the synchronous double cancer patients (3/4, 75%) were gastric cancer combined with CRC. Most of the CRC patients (15/17) were diagnosed by colonoscopy due to the presence of hematochezia or gastrointestinal symptoms/signs, while two CRC patients with severe bowel obstruction were diagnosed by abdominal computed tomography (Table 2). The most common clinical symptoms and signs included hematochezia, followed by abdominal pain, constipation, anemia, and ileus. To date, most patients have survived, but two stage IV patients died of CRC due to delayed diagnosis of the disease. DISCUSSION CRC is a leading cause of death in the Western world, and it has also become the third leading cause of death from cancer in Taiwan. Survival can be improved if the disease is detected earlier. Cancer-bearing patients are assumed to be at increased risk of developing cancers of other organs [4]. The rapidly increasing rate of CRC in recent years has drawn special attention to this site in terms of synchronous and metachronous malignancies of other organs. In this current investigation, the incidence of a second othersite primary cancer is 1.65%, which is within the range of % from previous reports [5 7]. Of these 17 cases, breast and gastric cancer patients had the highest risk of second cancer for CRC. Our results are consistent with those of a Japanese research group [5,8], where gastric cancer 548 Kaohsiung J Med Sci November 2006 Vol 22 No 11

3 Colorectal cancer patients with primary cancer of other organs Table 1. Demographic and clinical description of colorectal cancer (CRC) patients with primary cancers of other organs Age (yr)/ Interval between Patient Phase Location of CRC TNM stage (CRC) Histology Other malignancy gender cancers (yr) 1 66/F Metachronous Rectum T2N0M0 stage I MD Cervical cancer /F Metachronous Sigmoid colon T3N1M0 stage III WD Ovarian cancer /M Metachronous Sigmoid colon T2N0M0 stage I MD Lung cancer /F Metachronous Sigmoid colon T4N0M1 stage IV MD Basal cell carcinoma 2 of skin 5 66/F Metachronous Sigmoid colon T3N0M1 stage IV MD Thyroid cancer /M Metachronous Sigmoid colon T4N1M0 stage III MD Gastric cancer /M Metachronous Rectum T4N1M0 stage III PD Gastric cancer /F Metachronous Ascending and sigmoid T3N0M0 stage II PD Gastric cancer 12 colon (synchronous) (metachronous) Breast cancer 9 (metachronous) 9 62/F Metachronous Sigmoid colon T3N1M0 stage III WD Breast cancer /F Metachronous Sigmoid colon T3N0M0 stage II WD Breast cancer /F Metachronous Sigmoid colon T2N0M0 stage I WD Breast cancer /F Metachronous Sigmoid colon T2N0M0 stage I WD Breast cancer /F Metachronous Sigmoid colon T3N1M0 stage III MD Breast cancer /F Synchronous Descending colon T4N1M0 stage III MD Gastric cancer Within /M Synchronous Rectum T3N1M0 stage III PD Gastric cancer Within /M Synchronous Sigmoid T2N0M0 stage I WD GIST (stomach) Within /M Synchronous Rectum T3N0M0 stage II MD Urinary bladder cancer Within 1 MD = moderately differentiated; WD = well differentiated; PD = poorly differentiated; GIST = gastrointestinal stromal tumor. Kaohsiung J Med Sci November 2006 Vol 22 No

4 J.Y. Kan, J.S. Hsieh, Y.S. Pan, et al Table 2. Diagnosis of colorectal cancer (CRC) and treatment procedure for multiple cancers Clinical symptoms Preoperative Associated cancer and Histology of other Patient Procedure for CRC Outcome and signs examination procedure cancers 1 Hematochezia Colonoscopy Lower anterior resection Total hysterectomy SCC Alive 2 Hematochezia Colonoscopy Anterior resection Oophorectomy and Mucinous cystadenocarcinoma Alive total hysterectomy 3 Hematochezia Colonoscopy Low anterior resection Left lung lobectomy SCC Alive 4 Hematochezia Colonoscopy Hartmann s procedure Mohs surgical technique* BCC Alive 5 Hematochezia Colonoscopy Low anterior resection Total thyroidectomy Follicular carcinoma Death due to colon cancer 6 Ileus Abdominal CT Anterior resection Radical total gastrectomy Adenocarcinoma Alive colonoscopy 7 Hematochezia and Colonoscopy Loop colostomy Radical subtotal gastrectomy Adenocarcinoma Death due to constipation rectal cancer 8 Abdominal pain Abdominal CT Subtotal colectomy Modified radical mastectomy and Infiltrating ductal carcinoma Alive radical subtotal gastrectomy (grade II) and adenocarcinoma 9 Anemia Colonoscopy Anterior resection Modified radical mastectomy Infiltrating ductal carcinoma Alive 10 Abdominal pain and Colonoscopy Anterior resection Modified radical mastectomy Infiltrating ductal carcinoma Alive constipation 11 Hematochezia Colonoscopy Low anterior resection Breast conservative surgery Infiltrating ductal carcinoma Alive 12 Hematochezia and Colonoscopy Anterior resection Modified radical mastectomy Infiltrating ductal carcinoma Alive small caliber 13 Hematochezia Colonoscopy Anterior resection Modified radical mastectomy Intraductal carcinoma Alive 14 Ileus and Colonoscopy Subtotal colectomy Chemotherapy Adenocarcinoma Alive abdominal pain 15 Hematochezia and Colonoscopy Abdominoperineal Radical total gastrectomy Adenocarcinoma Alive bowel habit change resection 16 Hematochezia and Colonoscopy Anterior resection Radical subtotal gastrectomy GIST and CD117 staining(+) Alive anemia 17 Ileus Colonoscopy Abdominoperineal Right nephroureterectomy Transitional cell carcinoma Alive resection *Mohs surgical technique = horizontal sectioning of the depths of an excised skin cancer. SCC = squamous cell carcinoma; BCC = basal cell carcinoma; CT = computed tomography; GIST = gastrointestinal stromal tumor. 550 Kaohsiung J Med Sci November 2006 Vol 22 No 11

5 Colorectal cancer patients with primary cancer of other organs predominates among CRC patients with primary cancer of other organs. Ueno et al indicated that when colon cancer was combined with other cancers, stomach cancer (1.4%) was the most frequently encountered neoplasm, followed by breast cancer (0.4%); and when rectal cancer was combined with other cancers, stomach cancer (0.6%) was also the most frequently encountered neoplasm, but this was followed by lung cancer (0.5%) [5]. Consequently, we should closely follow up and ascertain the possibility of developing secondary CRC among gastric and breast cancer patients postoperatively. Conversely, our incidence of lung cancer together with CRC is only 0.1%, which is far less than the Japanese study. Another research group from Taiwan [7] observed that the most common second other-site primary cancer in CRC patients was the liver, and this was followed by the stomach. Recently, the decreasing incidence of hepatoma in Taiwan may possibly explain this phenomenon. Furthermore, there is an increased risk of developing breast or reproductive organ cancer in women who survive CRC [9 12]. Screening for colorectal tumors in women with a past history of breast, uterine, or ovarian malignancies is suggested [12]. It was reported that cervical cancer was the most predominant malignancy associated with CRC, followed by gastric cancer in the past [13]. However, with the increasing incidence of breast cancer in developed countries in recent years, breast cancer has become the highest risk malignancy accompanying CRC. Most patients have the symptoms and signs of hematochezia or bowel habit change, and the disease is usually diagnosed by colonoscopy. The essentials of colonoscopy for patients with previous malignancy must be kept in mind. A significantly higher proportion of TNM stage I CRC (29.4%) would be responsible for the favorable clinical outcomes of these patients in our investigations. Early diagnosis and surgical intervention should also be emphasized, though two patients were diagnosed as late as stage IV. We observed three gastric cancers of four synchronous second other-site primary cancers among our CRC patients, and these findings raised an issue of performing upper gastrointestinal endoscopy before management of CRC. Ueno et al suggested that all CRC patients should undergo screening by upper gastrointestinal endoscopy before operation [5]. In addition, they recommend repeated upper gastrointestinal endoscopy at 2-year intervals during the first 5 years after operation. However, its cost-effectiveness remains to be further evaluated. We suggest that CRC patients with gastrointestinal symptoms or signs should be carefully evaluated and checked up for the necessity of upper gastrointestinal endoscopy in advance. Precursor lesions (adenomatous polyps) almost always precede the development of the neoplasm by several years. In our study, one gastric cancer patient who had undergone transanal polypectomy 15 years previously and who was lost to follow-up unfortunately developed unresectable rectal cancer later. Systematic surveillance for second cancer is essential after cancer surgery. A good surveillance program should be cost-effective, and more detailed analysis is mandatory for the high-risk sites of developing second cancers. Breast and gastric cancer patients in particular have high risk for second cancers of CRC. Patients presenting with hematochezia or other gastrointestinal symptoms/signs should be carefully evaluated. REFERENCES 1. Parkin DM. Global cancer statistics in the year Lancet Oncol 2000;2: Health and National Health Insurance Annual Statistics Information Service. Department of Health, Taiwan. Available from: statistic/index.htm [Date accessed: January 2006] 3. Greene FL, Page DL, Fleming ID, et al (eds). AJCC Cancer Staging Handbook. New York: Springer-Verlag, 2001: Kobayashi Y, Arimoto H, Watanabe S. Occurrence of multiple primary cancer at the National Cancer Center Hospital Jpn J Cin Oncol 1991;21: Ueno M, Muto T, Oya M, et al. Multiple primary cancer: an experience at the Cancer Institute Hospital with special reference to colorectal cancer. Int J Clin Oncol 2003;8: Wang HZ, Huang XF, Wang Y, et al. Clinical features, diagnosis, treatment and prognosis of multiple primary colorectal carcinoma. World J Gastroenterol 2004;10: Chiang JM, Yeh CY, Changchien CR, et al. Clinical features of second other-site primary cancers among sporadic colorectal cancer patients a hospital-based study of 3,722 cases. Hepatogastroenterology 2004;51: Schoenberg BS, Greenberg RA, Eisenberg H. Occurrence of certain multiple primary cancers in females. J Natl Cancer Inst 1969;43: Howell MA. The association between colorectal cancer and breast cancer. J Chronic Dis 1976;29: Kaohsiung J Med Sci November 2006 Vol 22 No

6 J.Y. Kan, J.S. Hsieh, Y.S. Pan, et al 10. Agarwal N, Ulahannan MJ, Mandile MA, et al. Increased risk of colorectal cancer following breast cancer. Am J Gastroenterol 1984;79:822. [Abstract] 11. Lee TK, Barringer M, Myers RT, et al. Multiple primary carcinomas of the colon and associated extracolonic primary malignant tumors. Ann Surg 1982;195: Rozen P, Fireman Z, Figer A, et al. Colorectal tumor screening in women with past history of breast, uterine, or ovarian malignancies. Cancer 1968;57: Chen YR, Wang HM, Chen SS, et al. A clinical study of colorectal cancer accompanied by cancer of other organs. Chin Med J (Taipei) 1995;55: Kaohsiung J Med Sci November 2006 Vol 22 No 11

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