Surgical therapy of colon cancer
In the last 30 years progress in colon cancer therapy arose from an increasingly personalized approach to treatment, consistent implementation of oncological principles in surgery, more aggressive treatment protocols in metastatic disease, and the application of minimally invasive surgical techniques. In nonmetastatic colon cancer UICC II and III standardized treatment concepts in multinodal tumor therapy 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]. In metastasized cancer, 20% of patients achieve a five-year survival rate of more than 40 % [19].
Oncological principles in surgery
En-bloc resection of the tumor-bearing segment of the colon with systematic locoregional lymphadenectomy is of decisive importance for the prognosis. Systematic lymphadenectomy with a high yield of potentially metastatic lymph nodes is the basis for standardized classification of lymph node status, the resulting therapeutic recommendations 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 intermedian 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 10cm [25, 26]. The extent of the resection therefore depends on the region supplied by the primary arteries divided at their origins and should cover at least 10cm on both sides of the tumor. Being the last lymph node station, the primary lymph nodes are located centrally where the primary arteries arise from the main vessels.
Due to the increasingly performed standardized en-bloc resection with systematic lymphadenectomy, and considering the established chemotherapy protocols, the overall prognosis in curative settings has improved in the last 20 years [16]. Retrospective trials have demonstrated a non-stage dependent correlation between the number of lymph nodes examined and the prognosis [8, 13].
Outside of studies the concept of the sentinel lymph node has not proven its benefit as a staging tool in colon surgery [3, 4]. Even if the study data are ambiguous, as a quality criterion the current German S3 guideline"Colorectal carcinoma" recommends the excision and histological work-up of at least 12 lymph nodes [21].
In addition to systematic lymphadenectomy, the concept of Complete Mesocolic Excision (CME) also aims at a maximum reduction in the number of local recurrences by increasing the radical extent 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 to protect both mesocolic fascial laminae of the resection area and avoid possible tumor cell seeding.
- Strict division of the respective primary vessels as close to their origins as possible results in the maximum number lymph nodes as well as maximum local radicality centrad.
- A sufficient length of the resected specimen maximizes the 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), with surgeons of appropriate expertise single-center and multicenter RCTs (KOLOR, COST, CLASSIC-Trail) showed 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 carcinoma", laparoscopic resection of colon cancer may therefore be performed in appropriate cases, if the surgeon has suitable experience [21]. At present there is no evidence for the NOTES technique in colon cancer.
Multimodal tumor therapy
Numerous studies demonstrate the significance of medical tumor therapy in nonmetastatic colon cancer. Adjuvant chemotherapy in UICC stage III correlates with a significant improvement of about 20 % in the prognosis of overall survival[22]. In stage II, since patients at risk (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 treatment of locally advanced colon cancer has been studied. A randomized study in the UK on locally advanced colon cancer demonstrated that unlike adjuvant chemotherapy alone combined neoadjuvant/adjuvant chemotherapy (oxaliplatin, leucovorin and 5-FU) lowered the rate of R1 resection and resulted in significant downstaging. No tumor progression was observed while the neoadjuvant chemotherapy was ongoing [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 results are still pending.
Hepatic and pulmonary metastases
In metastasis, the five-year survival rate is less than 10%. Under medical tumor treatment (combination of dual therapy and antibodies) and with the more aggressive indication for metastasis resection, about 20% of metastasized patients will profit from a five-year survival rate of up to 50% [15]. The combination of different chemotherapy protocols results in response rates of up to 60% and an R0 resection rate of up to 15% [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 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 form. 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 intrabdominal 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].