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ORIGINAL ARTICLE
Year : 2016  |  Volume : 12  |  Issue : 4  |  Page : 1257-1260

The clinical and pathological features affecting the time of relapse in patients with early stage colorectal cancer


Department of Medical Oncology, Ankara Numune Education and Research Hospital, Ankara, Turkey

Date of Web Publication7-Feb-2017

Correspondence Address:
Doğan Yazilitas
Department of Medical Oncology, Ankara Numune Education and Research Hospital, 06100 Sihhiye, Ankara
Turkey
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.199527

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 > Abstract 

Background: The relapses of colorectal cancer (CRC) frequently occur in 2 years period after the time of diagnosis. However, a considerable proportion of patients relapse in the late period.
Aim: The aim of the present study is to define the factors predicting the early and late relapses of patients with early stage CRC.
Materials and Methods: A total of 250 patients with CRC, who relapsed after completion of primary therapy between 2005 and 2014, were enrolled in the study. According to the time of relapse, patients were divided into two groups as follows: Early relapse (Group 1: Within first 24 months) and late relapse (Group 2: Later than 24 months). Clinicopathological features and survival rates of the two groups were compared.
Results: Of 250 patients, 151 (60.4%) (Group 1) were relapsed within the first 24 months after completion of the primary therapy and 105 (39.6%) were relapsed later than 24 months. The patients with T1–T2 and Grade I tumors were relapsed in late period (P < 0.05). The rates of administered systemic chemotherapy and targeted therapies after relapse were similar in both groups. The median overall survival rates in patients relapsed within the first 24 months and after 24 months were 18 months and 21 months, respectively (P = 0.05).
Conclusions: In patients with CRC, the time duration of relapse after completion of the operation and adjuvant chemotherapy was a prognostic factor. Grade I and superficial tumors (T1–T2) are the predictors of late relapses (after >24 months). The patients relapsed within the first 24 months after primary therapy had poor prognosis compared to those who relapsed in late period.

Keywords: Colorectal cancer, prognosis, survival, time of relapse


How to cite this article:
Yazilitas D, Özdemir N, Yazıcı O, Hocazade C, Demirci NS, Zengin N. The clinical and pathological features affecting the time of relapse in patients with early stage colorectal cancer. J Can Res Ther 2016;12:1257-60

How to cite this URL:
Yazilitas D, Özdemir N, Yazıcı O, Hocazade C, Demirci NS, Zengin N. The clinical and pathological features affecting the time of relapse in patients with early stage colorectal cancer. J Can Res Ther [serial online] 2016 [cited 2020 Oct 25];12:1257-60. Available from: https://www.cancerjournal.net/text.asp?2016/12/4/1257/199527


 > Introduction Top


Colorectal cancer (CRC) is the third most frequently diagnosed cancer according to the United States of America data. It is the third leading cause of cancer-related deaths.[1] The curative treatment is surgery, and postoperative adjuvant radiotherapy and chemotherapy are administered based on the stage of the disease. After surgery, patients with CRC may present with local recurrence or distant metastasis. Various clinical and histopathological prognostic factors for recurrence have been proposed, including T-stage, lymph node involvement, grade, the number of the lymph nodes removed, status of surgical margins, urgent surgery, vascular invasion, and perinodal invasion.[2],[3],[4],[5],[6],[7],[8],[9],[10] Although the recurrences usually occur in the first 2 years, late recurrences may also occur. In this study, we aimed to analyze the factors that may predict early and late recurrences in patients with CRC.


 > Materials And Methods Top


In this study, medical records of 2200 patients diagnosed with early stage CRC treated and followed between 1993 and 2014 were analyzed. A total of 250 R0 resected patients were included in the study.

The patients were divided into two groups as follows: the ones who had recurrence within the first 24 months and the ones who had recurrence after 24 months. The demographic characteristics (age, gender, adjuvant or neoadjuvant therapy, tumor markers, etc.), histopathological characteristics (T-stage, lymph node involvement, presence of lymphovascular invasion, grade, histopathological subtype, etc.), progression-free survival, and overall survival (OS) of the two groups were analyzed and compared.

The baseline staging of the patients was updated according to the seventh version of American Joint Committee on Cancer TNM, by analyzing their histopathological findings. The patients were divided into two groups according to the site of recurrence as follows: visceral and nonvisceral. Visceral metastasis was defined as the metastasis to organs such as liver, lungs, and brain. Nonvisceral metastases were considered as colorectal recurrences, and metastases to peritoneum, lymph nodes, and bone. In case of both visceral and nonvisceral metastases, the patient was included in the visceral metastasis group.

Disease-free survival (DFS) was defined as the time from diagnosis to until local or distant metastasis, and OS was defined as the time interval between the date of diagnosis and the date of last follow-up.

Statistical analysis

Statistical analysis was performed using SPSS ® version 15.0 (SPSS Inc., Chicago, IL) software for Windows. Survival analyses were performed using Kaplan–Meier method.


 > Results Top


Baseline demographic characteristics

A total of 250 patients were included in the study. Of the 250 patients, 151 (60.4%) had recurrence within the first 24 months (Group 1) and 105 (39.6%) had recurrence later than 24 months (Group 2). The baseline demographic characteristics of the patients at the time of diagnosis are shown in [Table 1].
Table 1: Patient characteristics at time of diagnosis

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Males constituted 58% of all patients, the median age was 58 years (range 19–88), and there was not a statistically significant difference between the groups. The primary tumor located in rectum in half of the patients (52%), 20% of which were mucinous subtype. However, the difference was not statistically significant (P = 0.89 and P = 0.61). The rate of neo/adjuvant treatment was similar in both groups (P = 0.30). At the time of recurrence, carcinoembryonic antigen (CEA) and CA19-9 levels were detected high in 76% and 45.1% of the patients, respectively; however, no statistically significant difference was found between the groups (P = 0.18 and P = 0.31). Lymph node positivity, pathological stage, lymphovascular, and perineural invasion were similar between the two groups (P < 0.05).

Approximately 50% of all patients with recurrence had Grade I histopathology. The rate of patients with Grade I histopathology was significantly higher in late recurrence group (64.9% vs. 35.1%, P = 0.001). It was found that the recurrence developed later in T1–T2 tumors (6.0% vs. 15.3%, P = 0.05).

Visceral organ metastases constituted 54.2% of all recurrences while 45.8% of the recurrences were nonvisceral. The rate of visceral metastasis was 52.7% in the group that recurred within the first 24 months while this value was 56.6% in the group that had metastasis later than 24 months (P = 0.54). Among all patients, 31.6% had surgery for recurrence. The rates of surgery for recurrence were similar in both groups (P = 0.93).

Treatment characteristics and survival data at the time of recurrence

Median follow-up period was 14 months. Median time to recurrence was 13 months in Group 1 and 39 months in Group 2. The rate of chemotherapy administration after recurrence was 90% in both groups. The chemotherapy regimens were similar in both groups (P > 0.05) [Table 2].
Table 2: Patient characteristics at the time of recurrence

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OS was worse in patients who recurred within the first 24 months. Median survival was 18 months in Group 1 and 21 months in Group 2 (P = 0.05) [Figure 1].
Figure 1: Overall survival Kaplan Meier Curves of early stage CRC relapsed during 24 months and later than 24 months after diagnosis

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 > Discussion Top


A number of factors including the tumor histopathology related to patients have been reported for recurrence after curative treatment in CRC.[2],[3],[4],[5],[6],[7],[8],[9],[10] In this study, we aimed to determine the tumor-related characteristics, which could predict early or late recurrence or long-term survival data in early stage CRC.

In general, recurrences are more frequent within the first 2 years in CRC. In our study, approximately 40% of the patients recurred later than 2 years. Eighty percent of all recurrences were observed in the first 3 years. Time to recurrence was 13 months in Group 1, and 39 months in Group 2. Cho et al. reported that 18 of 352 patients with CRC had recurrence 5 years after the diagnosis.[11] Ryuk et al. compared the patients who had recurrence in the first 2 years versus later, and they reported that 29.8% of 222 patients had recurrence later than 2 years.[3]

The parameters that could affect the recurrence were analyzed, and it was found that late recurrences were more common in women; however, the difference was not statistically significant (P = 0.08). Tumor grade and T-stage were found to affect time to recurrence. The rate of Grade I tumors was significantly higher in the group that had late metastasis (35.1% vs. 64.9%, P = 0.001). T1–T2 stage in the primary tumor was found to be correlated with late metastasis (6%, 15.3%, P = 0.05). Similar to our study, Cho et al. reported that Grade I tumors showed late metastasis.[11]

Adjuvant treatment has been under debate in patients with lymph node-negative CRC. Surgery alone may be sufficient in patients with Stage I–II tumors since those patients have low recurrence rates.[2],[10] As expected, only 10% of our patients developing metastasis had T I-II tumor at the time of diagnosis, indicating similar findings to the study by Kobayashi et al.[12] Lan et al. reported the early and late recurrence rates in Stage I patients as 7% and 9%, respectively, while those rates were reported as 26% and 30.1%, respectively, in Stage II patients.[13]

The primary tumor located in rectum in approximately half of our patients. The localization of primary tumor was not found to be related to time of recurrence (P = 0.89). Sadahiro et al. performed a study on 418 patients and showed that time to recurrence was longer in patients with operated rectum cancer, compared with colon cancer patients (26 vs. 17 months, P = 0.03).[14] We measured the tumor markers' levels to determine whether they could indicate early and late metastases; however, we did not find a significant difference between the groups in terms of CEA and CA19-9 levels at the time of recurrence. In contrast, it was shown that CEA significantly increased in case of early recurrence in a study including 320 patients.[15]

Operated CRC patients may have local or distant metastasis. In both circumstances, a long survival may be achieved with surgery in selected patients, and one of the aims of the treatment is to render those patients suitable for metastasectomy.[16],[17],[18],[19] In our study, 54.2% of the recurrences were visceral and 45.8% were nonvisceral. There was no difference between the groups in terms of recurrence patterns (P = 0.54). Among all patients, 31.6% could have metastasectomy. We did not find a significant correlation between the time of recurrence and rate of surgery performing for recurrence (P = 0.93).

We analyzed the prognosis of patients who had recurrence within first 24 months versus after 24 months and found a significantly shorter time between recurrence and death (OS) in the group with early metastasis (18 vs. 21 months, P = 0.05). In their series of 222 patients, Ryuk et al. divided patients into two groups as the ones who had recurrence within 2 years and after 2 years.[3] They found 3-year survival worse in the patients who had early recurrence, indicating similar findings to our results (37.6% vs. 58.3%, P = 0.003). Bozkurt et al. performed a study in two centers and reported that the patients who recurred in the 1st year had poorer prognosis (P = 0.01).[20] Lan et al. performed a study in four centers, and compared OS of the patients who had recurrence within the first 3 years versus later, and unlike the other studies, they did not find significant differences between the groups (P = 0.94).[13] The possible reasons of this result may partly be due to choosing the 3 years as the cutoff point, which is a long time, and may be due to the fact that only 20% of the study group consisting of 400 patients had recurrence after 3 years.


 > Conclusions Top


A number of factors have been defined that could predict recurrence after curative surgery in early stage CRC. The parameters that could predict the time of recurrence have been investigated in a number of retrospective studies. Low-grade tumors and T1–T2 tumors are associated with a late recurrence. In addition, the recurrences that develop after a long DFS show a favorable prognosis. Given that 40% of all patients have recurrence later than 24 months, the risk for recurrence, particularly T1–T2 and Grade I tumors, must be taken into account during follow-up of the patients.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
 > References Top

1.
Siegel R, Desantis C, Jemal A. Colorectal cancer statistics, 2014. CA Cancer J Clin 2014;64:104-17.  Back to cited text no. 1
    
2.
André T, Boni C, Navarro M, Tabernero J, Hickish T, Topham C, et al. Improved overall survival with oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment in stage II or III colon cancer in the MOSAIC trial. J Clin Oncol 2009;27:3109-16.  Back to cited text no. 2
    
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Ryuk JP, Choi GS, Park JS, Kim HJ, Park SY, Yoon GS, et al. Predictive factors and the prognosis of recurrence of colorectal cancer within 2 years after curative resection. Ann Surg Treat Res 2014;86:143-51.  Back to cited text no. 3
    
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Griffin MR, Bergstralh EJ, Coffey RJ, Beart RW Jr, Melton LJ 3rd. Predictors of survival after curative resection of carcinoma of the colon and rectum. Cancer 1987;60:2318-24.  Back to cited text no. 6
    
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McArdle CS, Hole DJ. Emergency presentation of colorectal cancer is associated with poor 5-year survival. Br J Surg 2004;91:605-9.  Back to cited text no. 7
    
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Quah HM, Chou JF, Gonen M, Shia J, Schrag D, Landmann RG, et al. Identification of patients with high-risk stage II colon cancer for adjuvant therapy. Dis Colon Rectum 2008;51:503-7.  Back to cited text no. 8
    
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Cihan S, Kucukoner M, Ozdemir N, Dane F, Sendur MA, Yazilitas D, et al. Recurrence risk and prognostic parameters in stage I rectal cancers. Asian Pac J Cancer Prev 2014;15:5337-41.  Back to cited text no. 9
    
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Obrand DI, Gordon PH. Incidence and patterns of recurrence following curative resection for colorectal carcinoma. Dis Colon Rectum 1997;40:15-24.  Back to cited text no. 10
    
11.
Cho YB, Chun HK, Yun HR, Lee WS, Yun SH, Lee WY. Clinical and pathologic evaluation of patients with recurrence of colorectal cancer five or more years after curative resection. Dis Colon Rectum 2007;50:1204-10.  Back to cited text no. 11
    
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Kobayashi H, Mochizuki H, Sugihara K, Morita T, Kotake K, Teramoto T, et al. Characteristics of recurrence and surveillance tools after curative resection for colorectal cancer: A multicenter study. Surgery 2007;141:67-75.  Back to cited text no. 12
    
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Lan YT, Chang SC, Yang SH, Lin CC, Wang HS, Jiang JK, et al. Comparison of clinicopathological characteristics and prognosis between early and late recurrence after curative surgery for colorectal cancer. Am J Surg 2014;207:922-30.  Back to cited text no. 13
    
14.
Sadahiro S, Suzuki T, Ishikawa K, Tanaka Y, Marsuda T, Mukoyama S, et al. Recurrens patterns after curative resection of colorectal cancer in patients followed for a minimum of ten years. Hepatogastroenterology 2003;50:136-6.  Back to cited text no. 14
    
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Wedell J, Meier zu Esssen P, Luu TH, Fiedler R, van Calker H, Koldowski P, et al. A retrospective study of serial CEA determinations in the early detection of recurrent colorectal cancer. Dis Colon Rectum 1981;24:618-21.  Back to cited text no. 15
    
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Migliore M, Miloševic M, Lees B, Treasure T, Di Maria G. Finding the evidence for pulmonary metastasectomy in colorectal cancer: The PulMicc trial. Future Oncol 2015;11 2 Suppl: 15-8.  Back to cited text no. 16
    
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Kulaylat AN, Schubart JR, Stokes AL, Bhayani NH, Wong J, Kimchi ET, et al. Overall survival by pattern of recurrence following curative intent surgery for colorectal liver metastasis. J Surg Oncol 2014;110:1011-5.  Back to cited text no. 17
    
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Cokmert S, Ellidokuz H, Demir L, Fuzun M, Astarcioglu I, Aslan D, et al. Survival outcomes of liver metastasectomy in colorectal cancer cases: A single-center analysis in Turkey. Asian Pac J Cancer Prev 2014;15:5195-200.  Back to cited text no. 18
    
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Shao YC, Chang YY, Lin JK, Lin CC, Wang HS, Yang SH, et al. Neoadjuvant chemotherapy can improve outcome of colorectal cancer patients with unresectable metastasis. Int J Colorectal Dis 2013;28:1359-65.  Back to cited text no. 19
    
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Bozkurt O, Inanc M, Turkmen E, Karaca H, Berk V, Duran AO, et al. Clinicopathological characteristics and prognosis of patients according to recurrence time after curative resection for colorectal cancer. Asian Pac J Cancer Prev 2014;15:9277-81.  Back to cited text no. 20
    


    Figures

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    Tables

  [Table 1], [Table 2]



 

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