Clinical complete regression after local radiotherapy combined with chemotherapy for stage IV rectal cancer: A case report

  • Authors:
    • Yazheng Dang
    • Hongxiang Gao
    • Shigao Huang
    • Tao Qi
  • View Affiliations

  • Published online on: May 22, 2020     https://doi.org/10.3892/mco.2020.2049
  • Pages: 186-190
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Colorectal cancer is the fourth most common type of cancer worldwide with about 0.8 million new cases annually. Improving patient survival remains a challenge for clinicians. Observation waiting method provides improved quality of life compared with direct surgery. This case report suggested that colorectal cancer patients could choose active observation waiting method for treatment. A 59‑year‑old male patient, with rectal bleeding and an Eastern Cooperative Oncology Group (ECOG) performance status score of 0, was admitted to the hospital due to increased fecal blood volume. The electronic colonoscopy revealed multiple polyps in colon and rectum, whereas the pathological biopsy indicated poorly differentiated rectal adenocarcinoma. The clinical stage was defined as T3N2M1a according to the TNM classification of the American Joint Committee on Cancer (AJCC) staging manual (version 8). In addition, positron emission tomography/computed tomography (PET/CT) examination showed non‑regional lymph node metastasis (subclavian). Subsequently, the expression of PD‑L1 (‑), NRAS (‑), KRAS (‑), HRAS (‑), BRAF (‑) (‑, negative) and the microsatellite stability (MSS) were detected in the rectal cancer lesion using molecular pathological examination. Patients with primary rectal cancer and pelvic lymph node metastasis were treated with three‑dimensional conformal radiotherapy (3D‑CRT; dose, 60 Gy/30 Fr) and XELOX chemotherapy (200 mg oxaliplatin at day 1 plus 1.5  g capecitabine twice a day from day 1‑14 for a total of 5 cycles). PET/CT scan revealed that the metabolism levels of the lesion returned to normal. In addition, the routine re‑examination showed progressive improvement of tumor lesions. Until recently, the carcinoembryonic antigen (CEA) level of the male patient has been within normal range. The observation waiting method rather than the direct sequential surgical resection of the primary lesion in patients with advanced rectal cancer who achieved complete clinical remission (CCR) may provide a novel treatment method for rectal cancer. Thus, overall survival (OS) and quality of survival (QoS) differences between the two strategies need to be further verified by multicenter clinical trials.

Introduction

The incidence rate of colorectal cancer ranks fourth worldwide, with about 0.8 million new cases each year, accounting for 10% of all cancer types (1). Approximately 20% of patients present with advanced metastatic disease at initial diagnosis (2). Approximately 50-60% of colorectal cancer patients may develop local or distant metastases, mostly in liver and lungs, during the course of the disease, thus seriously threatening their life (3,4). Nowadays, oncologists are committed to ensuring improved survival rates and quality of life for patients. Thus, several studies have been conducted in recent years. Previous studies conducted on patients with locally advanced rectal cancer who achieved complete clinical remission (CCR) following preoperative neoadjuvant therapy, revealed no statistical significant differences in 3-year survival and local recurrence rates between observation waiting and direct surgery (5-7). Furthermore, the quality of life of the observation waiting patients was improved. Based on these observations, many researchers hypothesize that the active observation waiting method may be considered the appropriate treatment for patients with locally advanced rectal cancer.

Currently, the effect of active observation waiting in CCR in advanced rectal cancer has not been reported. In the present case report, the patient was actively observed and waited for nearly 1 year following CCR achievement via chemoradiotherapy. No sign of tumor recurrence was observed and the patient's quality of life was not affected. These observations provide novel aspects of advanced rectal cancer management.

Case report

A 59-year-old male patient, with rectal bleeding and an Eastern Cooperative Oncology Group (ECOG) performance status score of 0, was first admitted to the hospital in March 2018, and then followed up until May 2018. Electronic colonoscopy showed multiple polyps in the colon and rectum (Fig. 1A), whereas pathological biopsy indicated poorly differentiated rectal adenocarcinoma. The screening for rectal cancer and the evaluation of T stage were determined using positron emission tomography/computed tomography (PET/CT) and pelvic magnetic resonance imaging (MRI), respectively. The clinical stage was defined as T3N2M1a according to the TNM classification of the American Joint Committee on Cancer (AJCC) staging manual (version 8) (4). In addition, the PET/CT scan showed non-regional lymph node metastasis (subclavian). Finally, the expression of PD-L1 (-), NRAS (-), KRAS (-), HRAS (-), BRAF (-) and the microsatellite stability (MSS) were detected in rectal cancer using molecular pathological examination (Fig. 2A and B).

The male rectal cancer patient was treated with three-dimensional conformal radiotherapy (3D-CRT; dose, 60 Gy/30 Fr) and XELOX chemotherapy (200 mg oxaliplatin at day 1 plus 1.5 g capecitabine twice a day from day 1-14 for a total of 5 cycles) (Fig. 3). At the end of the first cycle, blood was not observed in the stool, and the electronic colonoscopy showed that the primary lesion was significantly shrunk and pathological type transformed into inflammation (Figs. 1B and 2C). Following XELOX chemotherapy, the carcinoembryonic antigen (CEA) levels were decreased from 282.7 to 10.3 ng/ml. One month later, CEA increased to 49.79 ng/ml (Fig. 4) and PET/CT scan revealed that the distant lymph nodes and the lymph nodes in the non-irradiated target sites were still active. Subsequentially, the residual lymph node underwent 3D-CRT (45 Gy/15 Fr) and the CEA level was further decreased to 25.58 ng/ml after 1 month. After 3 months the CEA levels were again increased to 154 ng/ml. The third PET/CT scan showed that the retroperitoneal lesion was reduced in size; however, recurrence of the pelvic lymph node was observed (Fig. 3). Therefore, the patient underwent systemic chemotherapy with FOLFIRI plus cetuximab for a total of 6 cycles. The individualized scheme gradually reduced the CEA level to 1.86 ng/ml and PET/CT re-examination indicated that the metabolism levels of the lesion returned to normal while the lesion was significantly reduced in size. Interestingly, his serum CEA level remained within normal range.

The study was approved by the Ethics Committee of the 986 Hospital of People's Liberation Army Air Force (file no. LZ 323-2018-07) and patient consent was obtained and provided.

Discussion

Currently, the median survival time of advanced rectal cancer has increased from 10 to 30 months (8). In order to ensure an increased survival time, patients and medical workers focus on improving the patient's quality of life. Thus, observation and waiting method is a challenging task for clinicians. This method may be considered a potential treatment for rectal cancer patients with unresectable concurrent metastasis, achieving CCR following preoperative neoadjuvant therapy, and especially for patients with initial diffuse lymph node metastasis.

The benefits of surgical excision of the primary lesion in advanced non-resectable rectal cancer are controversial. Faron et al reported that excision of primary lesions increased overall survival (OS) and progression-free survival (PFS) (9). However, a study by Cirocchi et al revealed that primary lesion resection did not affect OS, and lesion-related complications were not reduced in a comprehensive analysis based on large sample size (10). In addition to OS and PFS, the risk of surgery-related complications should not be ignored. Thus, previous studies have investigated the effect of primary lesion surgical resection on patients with advanced rectal cancer. The results showed that the postoperative complications, colostomy and 1-month mortality rates (for patients >65 years) were 30-50, 24 and 10%, respectively (11,12). Therefore, the surgical treatment in patients with non-resectable rectal cancer with initial simultaneous metastasis should be cautiously performed.

The rapid development of radiotherapy technology, novel cytotoxic drugs and targeted therapies have gradually weakened the therapeutic effect of surgery on advanced rectal cancer. A study has shown that FOLFIRI treatment with or without bevacizumab reduced primary lesion-related complications in patients with advanced unresectable rectal concurrent metastases without obvious obstruction or bleeding. Thus, surgical resection of the primary lesions was not recommended (13). In addition, 10-20% of patients achieved pathological complete response (pCR) following concurrent chemotherapy-radiotherapy, whereas the local recurrence, 5-year survival and disease-free survival rates were 4.6, 96 and 72%, respectively (14,15). Based on previous studies (14) and this first present case report, we hypothesize that patients exhibiting good response to systematic treatment may be treated by observing and waiting method, especially those >65 years of age. To the best of our knowledge, this is the first case study to report colorectal cancer, using the observation waiting method prior to non-surgical treatment.

Park et al have shown that the total survival time of patients with CCR was significantly increased compared with those without CCR (16). In the present case study, several factors contributed to the CCR achievement. Firstly, the ECOG score of the male patient case was 0 at the time of diagnosis. In addition, the immune function was basically normal prior treatment. Particularly, the number and proportion of CD8+ T and NK cells were within normal range, suggesting that immune function was not completely collapsed. This finding may explain the absence of liver or lung visceral metastasis, with only multiple lymph node metastasis observed. In addition, the patient did not suffer from other chronic diseases that could affect treatment response, such as inflammatory bowel disease, diabetes and the administration of immunosuppressive drugs (tacrolimus and cyclosporin) which demonstrated the patient had good compliance. Additionally, the treatment scheme was adjusted.

According to the 2019 National Comprehensive Cancer Network (NCCN) guidelines (version 2) (16), systemic translational treatment and local long- or short-term radiotherapy are recommended for advanced unresectable rectal cancer patients. In the present case study, the patient underwent local 3D-CRT radiotherapy [rectal lesions and pelvic lymph nodes; irradiation dose, DT, 60 Gy/30 Fr (17) followed by XELOX (18) systemic chemotherapy. The treatment scheme reduced the local tumor load and eliminated rectal bleeding. Following radiotherapy and chemotherapy, PET/CT examination indicated that the metabolism of the primary lesion was basically returned to normal and the pathological properties of the tumor changed from poorly differentiated adenocarcinoma to high-grade intraepithelial neoplasia. Following XELOX chemotherapy, the CEA levels were decreased from 282.7 to 10.3 ng/ml. With progress of the disease, local lymph nodes recurred and distant lymph nodes still exhibited increased metabolism levels. However, primary lesions were well controlled, reflecting the beneficial effect of radiotherapy in primary rectal cancer lesions. Following chemotherapy with FOLFIRI plus cetuximab regimen (19), the residual metastatic lymph nodes were completely relieved, and CEA and metabolism levels returned to normal. Furthermore, treatment was well tolerated by the patient, with no perforation, radiation proctitis and other complications, whereas only grade II hematology and gastrointestinal toxicity was observed. In addition, in terms of tumor characteristics, the pathologic features of the patient indicated common poorly differentiated adenocarcinoma, rather than mucinous adenocarcinoma characterized by poor prognosis or hepatoid adenocarcinoma characterized by AFP expression (18,20,21). At present, there is no consensus on the prognostic impact of RAS/RAF mutations in localized disease. Douillard et al (22) provided new information on different aspects of the RAS/BRAF mutations, together with a combination of BRAF mutations in serum and tumor MMR status. Neoadjuvant chemotherapy may be an option in the near future and plasma mutations may serve as a tool for relevant selection. Finally, whole-body PET/CT scan and CEA levels detection was performed during the treatment process in order for disease changes to be monitored (23). When the CEA levels were abnormally elevated, a PET/CT scan was performed in order for the tumor changes to be accurately evaluated in a timely manner. Thus, an effective local and whole-body antitumor treatment was performed, which significantly improved the antitumor effects.

In summary, there are many factors that affect the efficacy of advanced rectal cancer treatment and permanently eliminate interfering factors. Individualized and accurate treatment under the suggestion of multi-disciplinary specialist is an effective strategy to improve the CCR rate. Observation and waiting method may be a new treatment approach, rather than direct sequential surgical resection of the primary lesion, for patients with advanced rectal cancer who achieved CCR after non-surgical therapy. Thus, the differences between observation and waiting method, and direct sequential surgical resection on OS and QoS need to be further verified by multicenter clinical trials.

Acknowledgements

Not applicable.

Funding

There is no funding information.

Availability of data and materials

Data and materials are available from correspondence author.

Authors' contributions

YD, HG, SH designed the study and contributed to the study. SH reviewed and edited the manuscript, and TQ analyzed the data and supervised the study. All authors read and agreed to the final version of the manuscript.

Ethics approval and consent to participate

The study was approved by the Ethics Committee of the 986 Hospital of People's Liberation Army Air Force (file no. LZ 323-2018-07).

Patient consent for publication

Patient consent was obtained and provided.

Competing interests

The authors declare that they have no competing interests.

References

1 

Siegel R, Desantis C and Jemal A: Colorectal cancer statistics, 2014. CA Cancer J Clin. 64:104–117. 2014.PubMed/NCBI View Article : Google Scholar

2 

Isbister WH: Audit of definitive colorectal surgery in patients with early and advanced colorectal cancer. ANZ J Surg. 72:271–274. 2002.PubMed/NCBI

3 

Lee WS, Yun SH, Chun HK, Lee WY, Yun HR, Kim J, Kim K and Shim YM: Pulmonary resection for metastases from colorectal cancer: Prognostic factors and survival. Int J Colorectal Dis. 22:699–704. 2007.PubMed/NCBI View Article : Google Scholar

4 

Yoo PS, Lopez-Soler RI, Longo WE and Cha CH: Liver resection for metastatic colorectal cancer in the age of neoadjuvant chemotherapy and bevacizumab. Clin Colorectal Cancer. 6:202–207. 2006.PubMed/NCBI View Article : Google Scholar

5 

Bernier L, Balyasnikova S, Tait D and Brown G: Watch-and-wait as a therapeutic strategy in rectal cancer. Curr Colorectal Cancer Rep. 14:37–55. 2018.PubMed/NCBI View Article : Google Scholar

6 

Yahya J, Herzig D, Farrell M, Degnin C, Chen Y, Holland J, Brown S, Binder C, Jaboin J, Tsikitis VL, et al: Survey results of US radiation oncology providers' contextual engagement of watch-and-wait beliefs after a complete clinical response to chemoradiation in patients with local rectal cancer. J Gastrointest Oncol. 9:1127–1132. 2018.PubMed/NCBI View Article : Google Scholar

7 

Habr-Gama A, Perez RO, Nadalin W, Sabbaga J, Ribeiro U Jr, Silva e Sousa AH Jr, Campos FG, Kiss DR and Gama-Rodrigues J: Operative versus nonoperative treatment for stage 0 distal rectal cancer following chemoradiation therapy: Long-term results. Ann Surg. 240:711–717. 2004.PubMed/NCBI View Article : Google Scholar

8 

Mayer RJ, Van Cutsem E, Falcone A, Yoshino T, Garcia-Carbonero R, Mizunuma N, Yamazaki K, Shimada Y, Tabernero J, Komatsu Y, et al: Randomized trial of TAS-102 for refractory metastatic colorectal cancer. N Engl J Med. 372:1909–1919. 2015.PubMed/NCBI View Article : Google Scholar

9 

Faron M, Pignon JP, Malka D, Bourredjem A, Douillard JY, Adenis A, Elias D, Bouché O and Ducreux M: Is primary tumor resection associated with survival improvement in patients with colorectal cancer and unresectable synchronous metastases? A pooled analysis of individual data from four randomized trials. Eur J Cancer. 51:166–176. 2015.PubMed/NCBI View Article : Google Scholar

10 

Cirocchi R, Trastulli S, Abraha I, Vettoretto N, Boselli C, Montedori A, Parisi A, Noya G and Platell C: Non-resection versus resection for an asymptomatic primary tumor in patients with unresectable stage IV colorectal cancer. Cochrane Database Syst Rev. 8(CD008997)2012.PubMed/NCBI View Article : Google Scholar

11 

McCahill LE, Yothers G, Sharif S, Petrelli NJ, Lai LL, Bechar N, Giguere JK, Dakhil SR, Fehrenbacher L, Lopa SH, et al: Primary mFOLFOX6 plus bevacizumab without resection of the primary tumor for patients presenting with surgically unresectable metastatic colon cancer and an intact asymptomatic colon cancer: Definitive analysis of NSABP trial C-10. J Clin Oncol. 30:3223–3228. 2012.PubMed/NCBI View Article : Google Scholar

12 

Temple LK, Hsieh L, Wong WD, Saltz L and Schrag D: Use of surgery among elderly patients with stage IV colorectal cancer. J Clin Oncol. 22:3475–3484. 2004.PubMed/NCBI View Article : Google Scholar

13 

Poultsides GA, Servais EL, Saltz LB, Patil S, Kemeny NE, Guillem JG, Weiser M, Temple LK, Wong WD and Paty PB: Outcome of primary tumor in patients with synchronous stage IV colorectal cancer receiving combination chemotherapy without surgery as initial treatment. J Clin Oncol. 27:3379–3384. 2009.PubMed/NCBI View Article : Google Scholar

14 

Huang S, Dang Y, Li F, Wei W, Ma Y, Qiao S and Wang Q: Biological intensity-modulated radiotherapy plus neoadjuvant chemotherapy for multiple peritoneal metastases of ovarian cancer: A case report. Oncol Lett. 9:1239–1243. 2015.PubMed/NCBI View Article : Google Scholar

15 

Glynne-Jones R and Hughes R: Critical appraisal of the ‘wait and see’ approach in rectal cancer for clinical complete responders after chemoradiation. Br J Surg. 99:897–909. 2012.PubMed/NCBI View Article : Google Scholar

16 

Park IJ, You YN, Agarwal A, Skibber JM, Rodriguez-Bigas MA, Eng C, Feig BW, Das P, Krishnan S, Crane CH, et al: Neoadjuvant treatment response as an early response indicator for patients with rectal cancer. J Clin Oncol. 30:1770–1776. 2012.PubMed/NCBI View Article : Google Scholar

17 

Appelt AL, Pløen J, Harling H, Jensen FS, Jensen LH, Jørgensen JC, Lindebjerg J, Rafaelsen SR and Jakobsen A: High-dose chemoradiotherapy and watchful waiting for distal rectal cancer: A prospective observational study. Lancet Oncol. 16:919–927. 2015.PubMed/NCBI View Article : Google Scholar

18 

Goldberg RM, Sargent DJ, Morton RF, Fuchs CS, Ramanathan RK, Williamson SK, Findlay BP, Pitot HC and Alberts SR: A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer. J Clin Oncol. 22:23–30. 2004.

19 

Bokemeyer C, Van Cutsem E, Rougier P, Ciardiello F, Heeger S, Schlichting M, Celik I and Köhne CH: Addition of cetuximab to chemotherapy as first-line treatment for KRAS wild-type metastatic colorectal cancer: Pooled analysis of the CRYSTAL and OPUS randomised clinical trials. Eur J Cancer. 48:1466–1475. 2012.PubMed/NCBI View Article : Google Scholar

20 

McCawley N, Clancy C, O'Neill BD, Deasy J, McNamara DA and Burke JP: Mucinous rectal adenocarcinoma is associated with a poor response to neoadjuvant chemoradiotherapy: A systematic review and meta-analysis. Dis Colon Rectum. 59:1200–1208. 2016.PubMed/NCBI View Article : Google Scholar

21 

Ren F, Weng W, Zhang Q, Tan C, Xu M, Zhang M, Wang L, Sheng W, Ni S and Huang D: Clinicopathological features and prognosis of AFP-producing colorectal cancer: A single-center analysis of 20 cases. Cancer Manag Res. 11:4557–4567. 2019.PubMed/NCBI View Article : Google Scholar

22 

Douillard JY, Oliner KS, Siena S, Tabernero J, Burkes R, Barugel M, Humblet Y, Bodoky G, Cunningham D, Jassem J, et al: Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer. N Engl J Med. 369:1023–1034. 2013.PubMed/NCBI View Article : Google Scholar

23 

Perez RO, Habr-Gama A, Gama-Rodrigues J, Proscurshim I, Julião GP, Lynn P, Ono CR, Campos FG, Silva e Sousa AH Jr, Imperiale AR, et al: Accuracy of positron emission tomography/computed tomography and clinical assessment in the detection of complete rectal tumor regression after neoadjuvant chemoradiation: Long-term results of a prospective trial (national clinical trial 00254683). Cancer. 118:3501–3511. 2012.PubMed/NCBI View Article : Google Scholar

Related Articles

Journal Cover

August-2020
Volume 13 Issue 2

Print ISSN: 2049-9450
Online ISSN:2049-9469

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Dang Y, Gao H, Huang S and Qi T: Clinical complete regression after local radiotherapy combined with chemotherapy for stage IV rectal cancer: A case report. Mol Clin Oncol 13: 186-190, 2020.
APA
Dang, Y., Gao, H., Huang, S., & Qi, T. (2020). Clinical complete regression after local radiotherapy combined with chemotherapy for stage IV rectal cancer: A case report. Molecular and Clinical Oncology, 13, 186-190. https://doi.org/10.3892/mco.2020.2049
MLA
Dang, Y., Gao, H., Huang, S., Qi, T."Clinical complete regression after local radiotherapy combined with chemotherapy for stage IV rectal cancer: A case report". Molecular and Clinical Oncology 13.2 (2020): 186-190.
Chicago
Dang, Y., Gao, H., Huang, S., Qi, T."Clinical complete regression after local radiotherapy combined with chemotherapy for stage IV rectal cancer: A case report". Molecular and Clinical Oncology 13, no. 2 (2020): 186-190. https://doi.org/10.3892/mco.2020.2049