Surgical treatment in colon cancer
Progress in the treatment of colon cancer over the past 30 years has been driven by an increasingly personalized approach to treatment, consistent implementation of oncological principles in surgery, more aggressive treatment protocols in metastatic disease, and the advent of minimally invasive surgical techniques. In nonmetastatic colon cancer UICC II and III, standardized treatment concepts in multimodal tumor management have increased the mean five-year survival rate from 65% to over 85% and reduced the mean locoregional recurrence rate from over 13% to less than 2%. [10] [10]. In metastasized disease, 20% of patients achieve a five-year survival rate of 40 % and more. [19]
Oncological principles in surgery
En bloc resection of the tumor-bearing segment of the colon with systematic locoregional lymphadenectomy is crucial for the prognosis. Systematic lymphadenectomy with a high yield of potentially metastatic lymph nodes is the foundation for standardized classification of lymph node status, subsequent treatment recommendation, and patient prognosis.
In colon cancer centrad lymphatic metastasis spreads via the paracolic lymph nodes, which are affected in 70% of patients with nodal involvement, and via the intermediate lymph nodes to the lymph nodes along the primary artery. Longitudinal drainage along the sides of the tumor follows the paracolic lymph nodes with a maximum lateral spread of 10 cm. [25, 26] The extent of resection therefore depends on the region supplied by the primary arteries transected at their origins and should cover at least 10 cm on both sides of the tumor. The primary central lymph nodes, where the primary arteries arise from the main vessels, are the last lymph node station.
With the advent of standardized en bloc resection with systematic lymphadenectomy, an improvement in the overall prognosis in curative settings has been achieved over the past 20 years, even when compared with the established chemotherapy regimens. [16] Retrospective trials have demonstrated an association between the number of lymph nodes examined and prognosis independent of stage. [8, 13]
The sentinel lymph node concept has not gained acceptance as a staging tool in colon surgery outside trial settings. [3, 4] While the study data are conflicting, the current German S3 guideline "Colorectal Cancer" nevertheless recommends the resection and histological workup of at least 12 lymph nodes as one quality criterion. [21]
In addition to systematic lymphadenectomy, the concept of Complete Mesocolic Excision (CME) also aims for a maximum reduction in the number of local recurrences by increasing the radicality and quality of resection. The technique was published by Hohenberger et al. in 2009 and is based on three core concepts: [16, 24]
- Dissection along the embryonic layers, sparing both mesocolic fascial laminae of the resection area and thus avoiding possible tumor cell seeding.
- Strict division of the respective primary vessels as close to their origins as possible maximizes the number of lymph nodes as well as local radicality centrad.
- A resected specimen of appropriate length assures maximum paracolic lymphadenectomy.
Data from Denmark, Sweden and Germany show that in patients with colon cancer UICC stage I-III the CME technique correlates with better disease-free survival than in standard colon resection. [5, 6, 18]
Minimally invasive surgery
In terms of indicators of oncological quality (R status, number of lymph nodes) and long-term results (tumor recurrence, survival), single-center and multicenter RCTs (KOLOR, COST, CLASSIC-Trail) with surgeons of appropriate expertise revealed no difference between laparoscopic and open techniques in colon cancer surgery. [7, 11, 14] One benefit of minimally invasive surgery was a rather low short-term perioperative morbidity, while the overall morbidity and mortality remained unchanged. [23] According to the current German S3 guideline on "Colorectal Cancer", laparoscopic resection of colon cancer may therefore be performed in appropriate cases, if the surgeon has enough experience. [21] At present, there is no evidence for the NOTES technique in colon cancer.
Multimodal tumor therapy
Numerous studies demonstrate the significance of drug-based tumor management in nonmetastatic colon cancer. Adjuvant chemotherapy in UICC stage III correlates with a significant improvement of about 20% in the overall survival prognosis. [22] Since patients at risk in stage II (T4 tumor, perforated tumor, emergency surgery, number of studied/excised lymph nodes <12) have a significantly worse prognosis than same-stage patients without risk factors the former should be offered adjuvant chemotherapy. [21]
In recent years, the role of neoadjuvant chemotherapy in the management of locally advanced colon cancer has been studied. A randomized trial from the United Kingdom showed that in locally advanced colon cancer combined neoadjuvant/adjuvant chemotherapy (oxaliplatin, folic acid, and 5-FU) resulted in a lower rate of R1 resections and significant downstaging than adjuvant chemotherapy alone. Tumor progression with ongoing neoadjuvant chemotherapy was not observed. [2, 12] Studies have shown that computed tomography can identify the T-status of locally advanced colon cancer and thus select these patients for neoadjuvant chemotherapy or preoperatively assess their response to chemotherapy. [1, 20] However, long-term oncological outcomes are still pending.
Hepatic and pulmonary metastases
The five-year survival rate in metastasis is less than 10%. For about 20% of metastasized patients, drug-based tumor therapy (combination of dual therapy and antibodies) and more aggressive indication for metastasectomy significantly improves the prognosis with a five-year survival rate of up to 50%. [15] The combination of different chemotherapy protocols results in response rates of up to 60%. [9]
Peritoneal metastasis
If peritoneal metastases are already present in colon cancer, the indication for cytoreductive surgery followed by hyperthermal intraperitoneal chemotherapy (HIPEC) should be considered. This combined treatment protocol has demonstrated a significant survival benefit in terms of prolonging median survival from 12.6 to 22.3 months. [27] The extent of peritoneal metastasis is determined with the Peritoneal Cancer Index (PCI). If the PCI score in patients without additional extraabdominal metastases is below 20, surgical cytoreduction with HIPEC can be performed in specialized centers - provided R0 resection is possible. [21]
Perioperative concept
Most hospitals in Germany have implemented the ERAS concept ("enhanced recovery after surgery") of multimodal postoperative rehabilitation in gastrointestinal surgery, sometimes in modified versions. The concept aims to quickly control the pathophysiologic changes caused by the surgical intervention, such as fatigue, bowel atony, and insulin resistance. The concept includes early removal of gastric tubes and intraabdominal drains, early oral feeding, stimulation of bowel motility, effective analgesia (epi-/peridural), and early ambulation. Numerous studies have shown that the ERAS concept can significantly shorten the length of stay with a significantly lower complication rate. [17]