Journal of Surgical Oncology 51:179-182 (1992)

Colorectal Carcinoma in Young Patients KIMBERLY MARBLE, MD, S A U M I T R A BANERJEE, MU, AND LORI G R E E N W A L D , MD From the Department o f Surgery, Saint Francis Hospital and Medical Center (K.M., S.B., L.C.), Hartford, and the Department o f Surgery, University o f Connecticut School of Medicine (K.M.), Farmington, Connecticut ~~

Utilizing Tumor Registry records dating from 1935 to 1988, 50 patients diagnosed with colorectal adenocarincoma at the age of 40 years or younger were retrospectively studied with respect to sex, race, family history, delay in diagnosis, primary tumor location, tumor differentiation, mucin production, stage at presentation, and the effect of these factors on 5-year survival. This younger group of patients was compared to a computer-generated, randomly selected group of 50 patients 40 years of age or older. There was no difference with respect to sex, racial distribution, family history, symptoms at presentation, or expediency of physician diagnosis between the two groups. Younger patients waited significantly longer to seek medical attention than did their older counterparts. However, those patients who delayed presentation had no higher incidence of advanced disease than those patients who presented earlier. Younger patients had a higher incidence of poorly differentiated, advanced, rightsided tumors. This is in contrast to a predominance of well-differentiated, less advanced, rectosigmoid lesions in the older patients. There was no age-related difference in the incidence of mucin-producing tumors. Overall 5-year survival was 75% in older patients, in contrast to only 51% in younger patients ( P = 0.01). We conclude in this study that it is advanced stage at presentation that is the most significant prognostic indicator in patients of all ages. The high incidence of poorly differentiated, right-sided tumors is responsible for the majority of young patients presenting with advanced disease, resulting in their poorer prognosis. 0 1992 Wiley-Liss, Inc.

KEYWORDS:cancer, colon, rectum, youth, differentiation, survival, stage

INTRODUCTION During their lifetimes, 5% of the U.S. population will develop colorectal cancer [ 11. Each year, 140,000 Americans are diagnosed with this disease [ 11. The majority of these patients are in the sixth to seventh decade of life; however, 2-8% of such tumors occur in patients less than 40 years of age [2]. There is controversy in the current literature as to how this disease differs, if at all, in younger patients vs. older patients. Okuno [3] and colleagues from Japan, in a retrospective study 1987, concluded that younger patients had a significantly higher incidence of aggressive, mucinous tumors that presented at more advanced stages. The proposed mechanism for this is that copious mucin produc0 1992 Wiley-Liss, Inc.

tion causes a dissection within the colonic wall, thereby facilitating tumor spread [3]. Adkins and coworkers [4] from Vanderbilt University demonstrated an increased incidence of poorly differentiated tumors in this younger patient population. The study

Accepted for publication July 23, 1992. Address reprint requests to Dr. Kimberly Marble, 205 Vernon Ave., #163, Vernon, CT 06066. This paper was awarded third prize at the New England Cancer Society Fall Program, l0lst Meeting in Burlington, VT, on November 10, 1990. It was also presented at the Connecticut Chapter of the American College of Surgeons and the Connecticut Society of the American Board Surgeons 1990 Combined Meeting in Cromwell, CT, on December 12, 1990.

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TABLE I. Colorectal Carcinoma in Younger vs. Older Patients Studv Parameters

--

* Sex

-

Race Family history Predisposing conditions Delay in diagnosis Primary site Tumor differentiation Mucin production Stage at presentation 5-year survival

TABLE 11. Characteristics of Patients With Colorectal Carcinoma Diagnosed From 1935 to 1988

-

Sex Race FH PD

< 40 Years

> 40 Years

58% F 94% w 6% B 8% + 0%

52% F 98% w 2% B 6% + 0%

Key: F = Female, W = White, B = Black, FH = Family history, PD = Predisposing conditions, + = Positive.

n

5.5 rno

concluded that their poorer survival was due to the poorly differentiated nature of these tumors [4]. In contrast, Isbister and Fraser in New Zealand [ S ] concluded in a retrospective study that there is no difference in subsite incidence within the colon or in 10-year survival when comparing younger vs. older patient populations. Controversy persists in the current literature regarding whether or not colon cancer is a different disease in younger vs. older patients. The goal of our study was to answer this question.

PATIENTS AND METHODS We performed a retrospective study of our institution’s Tumor Registry records dating from 1935 to 1988. We reviewed 1,200 charts and found that, during this time period, 4% of all colorectal adenocarcinomas occurred in patients 40 years of age or younger. During the study period, a total of 50 younger patients were diagnosed with colorectal cancer. Their ages ranged from 14 to 40 years, with a mean age of 36. This group was compared to a computer-generated, randomly selected group of older patients diagnosed during the study period. Their ages ranged from 49 to 86 years, with a mean age of 70. Table 1 lists our study parameters. We investigated how these parameters compared in the two age groups and how these factors related to overall prognosis. The Chi-square method of statistical analysis was used to derive P values. Statistical significance was defined as a P value less than or equal to 0.01. Life table analysis was used to calculate 5-year survival rates. RESULTS There was no significant difference with respect to sex or racial distribution. The incidences of a positive family history of colon or rectal cancer were not significantly different between the two age groups. None of the patients in either group had a history of predisposing conditions such as ulcerative colitis or familial polyposis (Table ll).

5-

m v g time to presentation l A v g time to reach Dx

21

16rno

L ~

0

-

7

90% of both younger and older patients (Fig. 1). Comparative analysis of primary tumor location revealed that there was a significantly higher incidence of transverse and ascending colon lesions in the younger patient population, 54% compared to only 18% in older patients. In contrast, there were significantly more rectosigmoid lesions in the older patients, 76% compared to only 36% in younger patients (Fig. 2). In both age groups, right-sided tumors presented at more advanced stages. This predominance was most pronounced in the younger group. In the younger patient population, 96% of all right-sided tumors were either stage C or D. In the older patients, 55% of all right-sided tumors were stage C or D (Aster-Coller modification of the Duke’s classification).

Colorectal Carcinoma in Young Patients 540 yoa

>40 yoa

54% Right-Sided

76% Rectosigrnoid p=O.OOl, Chi square

p = O . O O I , Chi square

Fig. 2 . There was a higher incidence of right-sided colon cancers in younger patients (54%) in contrast to a higher incidence of rectosigmoid lesions in older patients (76%).

40 yoa

p=O.OI, Chi square p=O.OOl, Chi square

Fig. 3. Younger patients had a significantly higher incidence of poorly differentiated tumors than the older group (PD: poorly differentiated, WD: well differentiated).

The two patient populations were also compared with respect to the degree of differentiation exhibited by their primary tumors. Younger patients had a significantly higher incidence of poorly differentiated lesions, 40% compared to 2% in the older group ( P = 0.001, Fig. 3 ) . Of these poorly differentiated tumors, 90% were rightsided (P = 0.001, Fig. 4). In these younger patients, 85% of all poorly differentiated tumors presented at either stage C or D. This is in contrast to the 15% of moderately to well-differentiated tumors that presented at advanced stages ( P = 0.001). In contrast to the data reported by Okuno and colleagues [ 3 ] , we found no difference in the incidence of mucinous tumors between the two age groups, 16% vs. 12% for younger versus older patients, respectively. Furthermore, mucin production had no effect on 5-year survival in either of our patient populations. Overall, young patients presented with significantly more C and D lesions (54%) than did their older counterparts (32%) ( P = 0.01, Fig. 5 ) . As expected, life table

Fig. 5 . Younger patients presented with significantly more advanced tumors (stage C or D) than did their older counterparts.

TABLE 111. 5-Year Survival of Patients With Colorectal Carcinoma

A + B C + D Overall*

< 40 Years

> 40 Years

96% 23% 51%

78% 21% 75%

* P = 0.01

analysis of these data generated relatively low 5-year survival rates for all patients presenting with such advanced disease (Table 111). Four older patients were not entered into the life table analysis secondary to deaths not immediately related to their colorectal cancer (one myocardial infarction, two presumed arrhythmias, and one anesthesia-related death). The lower overall 5-year survival rate for younger patients (51%) compared to the older population (75%) is statistically significant ( P = 0.01). As patients with A and B lesions do relatively well, it is the higher incidence of C and D lesions in younger patients that reduces their overall 5-year survival (Table 111).

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DISCUSSION One question that arises in the current literature is whether or not the reported poor survival rates for younger patients are secondary to a more aggressive tumor type or simply secondary to a more advanced state of disease at presentation following a lengthy delay in diagnosis. Our goal was to determine whether young patients really do have a poorer prognosis than their older counterparts, and if so, why. We demonstrated statistically equivalent proportions of male and female patients, as well as equivalent racial distribution in both age groups. The incidence of a positive family history of colorectal carcinoma was the same for both age groups, and patients with a positive family history had no worse prognosis than did the other patients. Although younger patients had a konsiderably longer delay in diagnosis, it was not due to failure of physicians to reach the correct diagnosis in a timely manner. Rather, the delay was secondary to younger patients waiting, on the average, several months to seek medical attention for their symptoms. We could not, however, demonstrate a correlation between delay in diagnosis and more advanced disease at presentation. We have demonstrated in this study that younger patients have a higher incidence of right-sided tumors compared to older patients, who have a predominance of rectosigmoid lesions. In the younger patient population,

the majority of these right-sided tumors were poorly differentiated and presented at an advanced stage. It is well known that right-sided lesions frequently are advanced at the time of presentation because of their lack of early symptoms. However, our study is the first to report a higher incidence of poor histologic differentiation in right-sided tumors compared to left-sided tumors. It is advanced stage at presentation that is the most significant prognostic indicator in patients of all ages. The results of this study indicate that younger patients have a poorer overall 5-year survival rate because of their higher incidence of advanced stage of disease at presentation. We have also demonstrated that it is the high incidence of poorly differentiated, right-sided tumors that causes the majority of younger patients to present with advanced disease, not simply a delay in diagnosis.

REFERENCES I , Cady B: “Cancer Manual,” 7th ed. Boston: American Cancer Society, 1986, pp 212-213. 2. Jarvinen HJ, Turunen MJ: Colorectal carcinoma before 40 years of age: Prognosis and predisposing conditions. Scand J Gastroenerol I9:634-638, 1984. 3. Okuno M, Ikehara T, Nagayama M, et al: Colorectal carcinoma in young adults. Am J Surg, 154:264-268, 1987. 4. Adkins RB, DeLozier JB, McKnight WG, Waterhouse G: Carcinoma of the colon in patients 35 years of age and younger. Am Surg 53(3):141-145, 1987. 5 . Isbister WH, Fraser J: Large bowel cancer in the young: A national survival study. Dis Colon Rectum 33(5):363-366, 1990.

Colorectal carcinoma in young patients.

Utilizing Tumor Registry records dating from 1935 to 1988, 50 patients diagnosed with colorectal adenocarcinoma at the age of 40 years or younger were...
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