Evidence - Rectal resection, robot-assisted with total mesorectal excision (TME)

Staging diagnostics:

• Complete colonoscopy
  • Gold standard in the diagnosis of colorectal cancer
  • for localization diagnostics and for histological confirmation and to rule out a second cancer (about 5% of cases)
  • If the entire colon is visible endoscopically, CT or MR colonography can be used.
  • After emergency surgery (ileus, tumor perforation, endoscopically uncontrollable bleeding): postoperative colonoscopy after anastomosis healing and patient recovery to rule out synchronous double cancer
• Histological confirmation
• Laboratory analysis with determination of the CEA value

Note: At the time of initial diagnosis, about 30% of all colorectal cancers have an elevated tumor marker CEA and should therefore be determined preoperatively. In tumor follow-up, CEA is a reliable indicator of recurrence in marker-expressing tumors and is also an independent prognostic factor in the case of liver metastases. The significance of CA 125 as a progression parameter for further treatment of proven peritoneal carcinomatosis is currently unclear (1, 2). CA 19-9 is discussed as another tumor marker for recurrence, but it does not increase the diagnostic value regarding the presence of a recurrence compared to a sole determination of the CEA value. 

• Chest X-ray in 2 planes
• Ultrasound of the abdomen
• MRI of the small pelvis
• Rectal endosonography
• If necessary, CEUS (contrast-enhanced ultrasound) in case of suspected hepatic filiation
• If necessary, MRI liver in case of suspected hepatic filiation

Note: Although the S3 guideline considers a CT abdomen or CT thorax-abdomen unnecessary, it is still performed in most clinics. It serves not only to detect hepatic filiae but also to assess the primary tumor, possibly enlarged lymph nodes, and to assess the spatial relationship of the tumor-bearing colon to other structures, such as the ureters and their course.

From (3): Körber et al.: S3 guideline colorectal cancer, guideline program oncology of AWMF, German Cancer Society e.V. and German Cancer Aid. Status: 2019. Retrieved on: 03.07.2019.

Interdisciplinary tumor conference:

All patients with colorectal cancers should be presented in an interdisciplinary tumor conference after completion of primary therapy (e.g., surgery, chemotherapy). A study from the UK showed that this approach significantly increased patient survival (4).

Patients in the following constellations should be presented pre-therapeutically (3):

• any rectal cancer
• any colon cancer in stage IV
• distant metastases
• local recurrences
• before any locally ablative procedure

TNM classification:

The TNM system for rectal cancer is defined as follows (5):

In Germany, the recommendations for the treatment of colon and rectal cancer are anchored in the S3 guideline (S3 guideline colorectal cancer (Guideline program oncology (German Cancer Society, German Cancer Aid, AWMF): S3 guideline colorectal cancer. Status: 30.11.2017. valid until 29.11.2022, Retrieved on: 14.04.2023)

The UICC stages are as follows:

Height classification of rectal cancers:

For treatment planning, rectal cancers should be classified according to their distance from the anal verge (according to UICC):

Lower rectal third < 6 cm

Middle rectal third > 6 – 12 cm

Upper rectal third > 12 – 16 cm

Treatment planning

The treatment of rectal cancer is derived from the TNM and UICC stages determined in diagnostics (3):

(TAR: total anterior rectal resection, TEM: transanal microsurgery, HIPEC: hyperthermic intraperitoneal chemotherapy, PCI: Peritoneal Carcinomatosis Index)

Surgical procedure:

In rectal cancer, curative therapy usually requires not only the resection of the primary tumor in healthy tissue (i.e., with sufficient safety margin) but also the removal of the regional lymphatic drainage area with ligation of the inferior mesenteric artery at least distal to the origin of the left colic artery (so-called low tie) and partial or total removal of the mesorectum (PME=partial mesorectal excision, TME=total mesorectal excision). The proximal ligation of the inferior mesenteric artery (so-called high tie) has no prognostic significance, but it is often performed for technical reasons to ensure sufficient mobilization of the left hemicolon for reconstruction (6).

Only in strictly selected cases is curative resection possible through local measures. This includes small tumors (<3cm) that are well differentiated (G1, G2) and do not involve lymphatic vessels or blood vessels (L0, V0) (so-called low-risk situation). The so-called TEM (transanal microsurgery) should be used in this case (7, 8).

Cave: In T1 high-risk tumors (G3/4 and/or lymphatic vessel invasion) and in T2 tumors, the occurrence of lymph node metastases is 10–20%, so that sole local excision cannot be recommended according to guidelines (3).

Note: If a high-risk constellation is only revealed post resection after local resection, a radical-oncological operation should be performed within one month (9, 10). If the patient refuses this, adjuvant radio-chemotherapy may be offered as a case-by-case decision by the tumor board to improve prognosis.

TME/PME is understood as sharp dissection along anatomical structures between the visceral and parietal pelvic fascia with complete removal of the mesorectum in cases of cancer of the middle and lower rectal thirds and partial mesorectal excision in cases of cancer of the upper rectal third.

Cave: It is important to preserve the autonomous pelvic nerves (hypogastric nerves, inferior and superior hypogastric plexus).

The indications for robot-assisted deep anterior rectal resection therefore include:

• histologically confirmed malignant neoplasm of the rectum
• endoscopically non-removable or incompletely removable with high-grade intraepithelial neoplasia
• any deeper tumor mass in the rectum with a high suspicion of a malignant process

The indication for the surgical procedure in rectal cancer fundamentally depends on the tumor localization, especially the relation to the dentate line and the levator muscles, the depth of infiltration, and the sphincter function. Whenever possible, sphincter-preserving procedures should be preferred, weighing the subsequent quality of life. In cases of poor sphincter function, a permanent colostomy should be preferred instead of a deep anterior resection, which is then performed as rectal extirpation or pelvic floor preservation depending on the safety margin to be achieved from the pelvic floor.

If an adequate safety margin cannot be ensured by a deep anterior rectal resection, the following procedures should be applied depending on the exact height localization and possible infiltration:

• the intersphincteric rectal resection
• the abdominoperineal rectal extirpation,

Safety margins

For tumors of the upper rectal third (>12 -16 cm from the anal verge), the rectum is transected 5 cm distal to the macroscopic tumor margin. In addition, PME is performed here. A so-called coning (conical shaping of the resection towards distal) should be avoided.

Cave: In T3 and T4 tumors, satellite nodes or lymph node metastases can occur up to 4 cm distal to the macroscopic tumor margin (11, 12).

Without neoadjuvant therapy, a safety margin of 1-2 cm in situ should be maintained for low-grade tumors with good or moderate differentiation in the lower rectal third. For high-grade tumors (G3/4), a larger safety margin should be sought.

For distal tumors of the lower third, after neoadjuvant radio-chemotherapy to avoid otherwise necessary extirpation, an aboral distance of 0.5 cm may also be sufficient.

Note: It is absolutely necessary to perform an intraoperative frozen section to confirm tumor-free status of the distal resection margin.

For tumors of the middle and lower rectal thirds, total mesorectal excision (TME) should be performed up to the pelvic floor.

Reconstruction after total mesorectal excision

The deep and ultra-deep rectal resection with anastomosis can be associated with massive and extremely burdensome functional bowel emptying disorders for the respective patients. In principle, various anatomical reconstruction options exist. A straight end-to-end descending rectostomy should be avoided (13). The disadvantages manifest in increased stool frequency as well as poorer continence and quality of life.

Among the various reconstruction forms, the advantages regarding functional outcomes are best documented for the colon J-pouch. The transverse coloplasty pouch is inferior to the J-pouch (14). Possibly equivalent to the colon J-pouch is the side-to-end descending rectostomy, which many prefer due to its easier feasibility.

Extirpation

If the sphincters or the anal canal are infiltrated, abdominoperineal extirpation should be performed (3). Here, the extralevator cylindrical resection is recommended from an oncological perspective (15).

Procedure in case of complete response after neoadjuvant therapy

In cases where no tumor is detectable clinically (DRU), endoscopically, or radiologically (MRI) after neoadjuvant therapy (see below), surgery can be omitted (16).

This is evidenced, among other things, by the meta-analysis by Dattani et al. from 2018, which includes 17 studies with a total of 692 patients. There were 153 (22.1%) local recurrences, of which 96% (n = 147/153) occurred in the first three years of follow-up. The cumulative 3-year risk of local recurrence was 21.6% (95% CI, 16.0-27.8). A salvage operation was performed in 88% of the patients, of whom 121 (93%) received a complete resection (R0). 57 metastases (8.2%) were discovered, and 35 (60%) were isolated, without signs of synchronous regrowth; the 3-year incidence was 6.8% (95% CI, 4.1-10.2). The 3-year overall survival rate was 93.5% (95% CI, 90.2-96.2).

Prerequisite for a watch and wait approach is the thorough explanation to the patient and their willingness to undergo close follow-up. The duration of follow-ups should be at least 5 years, and these patients should also be included in studies and registries. An international expert consensus suggests the following follow-up intervals and diagnostics for 5 years: for three years every 3 months CEA, then every six months; for two years every 3 months DRU, MRI, and endoscopy, then every six months; for 5 years CT thorax/upper abdomen months 6,12,24,36,48,60 (17).

Stoma

In deep anterior rectal resection with TME, a temporary stoma is created. In such a so-called deviation stoma, ileostomy and colostomy are to be considered fundamentally equivalent. There are good arguments for both stoma entities. In recent meta-analyses, the ileostomy is favored in the absence of renal dysfunction (18, 19).

Although a stoma does not reduce the incidence of anastomotic insufficiency, it lowers morbidity, especially regarding clinically relevant anastomotic leakages and urgent relaparotomies (20). Stoma placements should always be discussed and marked preoperatively with the patient. Ileostomies are placed at least 1 cm prominent, colostomies slightly prominent (3).

Laparoscopic surgery for colorectal cancer

Mono- and multicentric RCTs (KOLOR, COST, CLASSIC trial) showed no differences in surgical-oncological quality indicators (R-status, number of lymph nodes) and long-term outcomes (tumor recurrences, survival) between laparoscopic and open techniques in colon cancer surgery with appropriate surgeon expertise (21-22).

The advantage of minimally invasive surgery was demonstrated in the short term with relatively low perioperative morbidity while overall morbidity and mortality remained unchanged (23).

In the long term, no differences were found between laparoscopic and conventional surgery regarding the rate of incisional hernias and adhesion-related relaparotomies or tumor recurrences (24, 25). The British CLASSIC study also confirms the oncological safety of laparoscopic surgery for colorectal cancers (26).

According to the current S3 guideline "Colorectal Cancer," a laparoscopic resection of colon cancer can therefore be performed in suitable cases with appropriate surgeon experience (3).

Robotic surgery for colorectal cancer

Robotic surgery, as an advancement of laparoscopic surgery, offers higher precision in instrument handling as well as improved visualization, with fundamentally great optimization potential compared to simple laparoscopy, especially regarding oncological abdominal surgery. Especially in rectal cancer, robotics could compensate for the disadvantages of standard laparoscopy in confined spaces, here in the small pelvis. However, to assert this safely, strong evidence is required.

At the time of the creation of the German S3 guidelines, the evidence for robotic surgery was assessed as insufficient. At that time, there were no meaningful prospective randomized studies on the value of robotics in colorectal cancer. Due to the lack of short- and especially oncological long-term results at the time of guideline creation, robot-assisted surgery for colon cancer is currently not recommended outside of studies (3). The new guideline, which is soon to be published, is eagerly awaited.

Studies have now shown that robotic surgery can be safely applied in colorectal cancer and has advantages in terms of tissue preservation and reduction of postoperative functional disorders.

The best data on robotic versus conventionally laparoscopic colorectal oncological surgery with early postoperative results and also oncological long-term results are available for rectal resections and for right hemicolectomy.

Lorenzon et al. included 18 case-control studies and 3 RCTs in their meta-analysis (27). The aim was to compare early postoperative results between robot-assisted and conventionally laparoscopically performed colorectal resections. The results from the RCTs showed no differences between robot-assisted and conventionally laparoscopically resected patients regarding operation time, length of hospital stay, or postoperative morbidity. When considering all studies and all colorectal resections, lower costs and shorter operation times were found for laparoscopically operated patients, whereas robotically operated patients had slightly lower morbidity (Odds Ratio=0.6-0.9)

A milestone regarding robotic surgery for rectal cancer is the Robotic Versus Laparoscopic Surgery for Middle and Low Rectal Cancer study (REAL) (28). The aim of the study was to generate high-quality evidence regarding short-term and long-term effects of robotic versus laparoscopic total/partial mesorectal excision (TME/PME). The REAL study was designed as an RCT (randomized controlled trial). It included randomization of patients with histologically confirmed rectal cancer ≤10cm from the anal verge (middle third) or ≤5 cm from the anal verge (lower third) in clinical stages cT1–T3 N0–N1, cM0 or ycT1–T3 Nx, cM0. Patients were randomized into robotic versus conventional laparoscopic arms. The primary endpoint is the 3-year local recurrence rate (data not yet published). Secondary endpoints are the rate of positive circumferential resection margin (CRM+) and the 30-day complication rate (at least Clavien-Dindo grade II). In 3 years, a total of 1240 patients from 11 centers were included and randomized (620 vs. 620). In the result, significantly fewer patients in the robotic group had a positive CRM (22/547 patients (4%) versus 39/543 patients (7.2%; p= 0.023)). Additionally, the number of removed lymph nodes was higher in the robotic group (median 15.0 (IQR 13.0–19.0) versus 14.0 (IQR 1.0–4.0); p= 0.006). The rate of postoperative complications within 30 days was also lower in the robotically operated group (16.2% versus 23.1%; p= 0.003). Intestinal motility resumed faster in the robotically operated group, and patients had a shorter hospital stay. Finally, the rate of clinically relevant anastomotic leakages was also slightly lower in the robotic group at 5.1% versus 8.2% (p= 0.057).

Thus, the REAL study provides high-level evidence that (in the hands of technically skilled surgeons) robotic surgery for middle and lower third rectal cancer shows better short-term results than conventional laparoscopy and particularly improves the oncological quality of rectal resections (29).

Finally, it should be noted that in colorectal centers that enter data into the DGAV registry, it is evident from benchmarking that robotics has led to an improvement in perioperative results and contributed to excellent oncological outcomes (30). Furthermore, it is evident that the proportion of successfully minimally invasive operated patients without conversion is higher in robotics than in conventional laparoscopy and that significantly fewer contraindications exist.

The cost aspect of robotics also plays a significant role in the discussion. For example, in a meta-analysis by Solaini, robotic-assisted procedures were associated with significantly higher costs (31). However, it should not be neglected that after the successful establishment of the robotic system, savings potential beyond acquisition and material costs arise. In German centers that have established robotics for colorectal cancer, it is generally observed that the length of stay for robotically operated patients is reduced compared to conventionally laparoscopically operated patients, and that it is generally – except in multimorbid patients – no longer necessary to maintain a monitoring bed.

Multivisceral resection

In cases where a tumor adheres to neighboring organs, it is not possible for the surgeon to safely determine macroscopically whether it is an infiltration of the carcinoma into the neighboring organ or merely a peritumoral inflammatory reaction. In such cases, biopsies and rapid section examinations should be strictly avoided, as there is always a risk of local tumor cell dissemination. This is always associated with a significant worsening of prognosis. Therefore, if technically feasible, an en-bloc resection of the tumor with the infiltrated structures is recommended (multivisceral resection) (32). In the case of rectal cancer, a complete pelvic exenteration may be required. Procedures with suspected infiltration of neighboring organs should always be discussed and planned preoperatively with the corresponding specialist department (gynecology, urology).

Ileus in rectal cancer

Since an ileus in connection with rectal cancer is usually associated with a far-advanced carcinoma, neoadjuvant radio-chemotherapy is almost always indicated. Therefore, to gain time for this, a transverse stoma is often placed primarily in this situation (3).

Multimodal tumor therapy

The progress in the treatment of rectal cancer over the last 30 years is due to an increasing individualization of therapy, the consistent implementation of surgical-oncological principles, more aggressive treatment regimens in the metastatic stage, and the use of minimally invasive surgical techniques. Standardized treatment concepts in multimodal tumor therapy have led to an increase in the average five-year survival rate as well as a reduction in the locoregional recurrence rate.

Procedure:

Neoadjuvant therapy for non-metastatic rectal cancer (3)

· UICC stage I: No neoadjuvant therapy recommended

· UICC stage II and III

• Middle and lower third: neoadjuvant radio-chemotherapy or short-term radiation
• Exceptions: Primary surgical approach possible:
  • cT1/2 tumors in the lower and middle third with radiologically questionable lymph node involvement
  • cT3a/b tumors in the middle third with limited infiltration into the perirectal fat tissue in MRI and without suspicion of lymph node metastases or extramural vascular invasion
• Upper third: tumors with high risk for local recurrences: consider neoadjuvant radio-/radiochemotherapy

· Implementation: Two schemes are established:

• Conventionally fractionated neoadjuvant radio-chemotherapy, operation after 6–8 weeks
  • 45–50.4 Gy total dose
  • 5-FU iv or Capecitabine po
  • Indications: Especially when downsizing is aimed at, i.e., in the case of
    • T4 tumors
    • Deep-seated tumors with planned sphincter preservation
    • <1–2 mm tumor distance to the mesorectal fascia
    • Following complete restaging, choose the surgical procedure
• Radiotherapy as short-term radiation (5×5 Gy)
  • Followed by surgery within 10-14 days
  • With extended interval until surgery
  • Interval 4–8 weeks: If downsizing is necessary and chemotherapy is contraindicated (as an alternative to conventionally fractionated radio-chemotherapy)
  • Interval up to 12 weeks: If downsizing is aimed at, combination with or without chemotherapy possible

Adjuvant therapy for non-metastatic rectal cancer

• UICC stage I and II with R0 resection: no adjuvant therapy recommended
• UICC stage II and III in the upper third without neoadjuvant therapy
  • Analogous to colon cancer
  • In the UICC stage II it is a so-called "may situation," i.e., depending on risk factors and microsatellite status, it can certainly be recommended. In the case of microsatellite instability, no adjuvant chemotherapy is recommended. If risk factors are present, adjuvant chemotherapy should be considered. Selected risk situations include: T4 tumor, tumor perforation/tear, surgery under emergency conditions, insufficient number of examined lymph nodes.
  • In the UICC stage III, adjuvant therapy is recommended.

Note: RCTs to determine the ideal timing of adjuvant therapy do not exist. In a retrospective analysis of cohort studies, an inverse correlation was calculated between the timing of the start of adjuvant chemotherapy and survival(33). This was also confirmed in further analyses(34).

• Duration: 3–6 months, depending on risk-benefit assessment
• UICC stage II: Monotherapy with fluoropyrimidines
• UICC stage III: Combination therapy with oxaliplatin
• FOLFOX: Folinic acid + 5-FU in combination with oxaliplatin
• XELOX (CAPOX®): Capecitabine + oxaliplatin
• In patients >70 years, therapy with oxaliplatin should not be performed
• In case of contraindications against oxaliplatin, monotherapy with fluoropyrimidines should be performed

Note: Adjuvant chemotherapy should not be omitted solely for age reasons. However, there is no sufficient evidence for the administration of adjuvant chemotherapy in patients over 75 years.

• UICC II and III in the lower third after previous neoadjuvant radio-chemotherapy:
  • The duration of perioperative chemotherapy should add up to about 6 months in total.
  • No clear recommendation for or against adjuvant chemotherapy according to the current guideline.
  • Current practice: Offering adjuvant chemotherapy with optimal fluoropyrimidine schemes.
• UICC II and III in the lower third without previous neoadjuvant therapy:
  • Adjuvant or additive radio-chemotherapy is recommended in the presence of risk factors for local recurrence, such as:
    • Stage: pN2, pT3 in the lower rectal third (for other tumor localization from pT4)
    • R1 resections
    • Intraoperative tumor perforation
    • Insufficient TME quality
    • pCRM+
  • A general recommendation for postoperative radio-chemotherapy for all patients with tumors in UICC stages II and III cannot therefore be made.
  • If no adjuvant radio-chemotherapy is performed after primary R0 resection in stage II/III, adjuvant chemotherapy should be performed analogous to the indication criteria and schemes for colon cancer.
  • Patients after a primary resection, in whom no neoadjuvant radio-chemotherapy has been used, can be treated adjuvantly according to data from the SCOT study in analogy to colon cancer (i.e., 3 or 6 months depending on risk profile, see colon cancer) (35).

Requirements

• Requirement for adjuvant therapy is the R0 resection of the primary tumor. The basis for the indication for adjuvant therapy after quality-assured tumor resection is the pathohistological staging, especially the determination of the pN status. To determine pN0, 12 or more regional lymph nodes should be examined (UICC 2002). Immunocytological findings of isolated tumor cells in bone marrow biopsies or lymph nodes as well as cytological tumor cell findings in peritoneal washings are not an indication for adjuvant therapy outside of studies.

General contraindications

• Poor general condition (ECOG >2),
• severe infection
• limited life expectancy due to comorbidities
• liver cirrhosis in Child B or C stage
• Severe coronary heart disease or heart failure (NYHA III and IV)
• Advanced renal insufficiency ((pre-)terminal)
• Blood formation disorders, impaired bone marrow function
• Inability to participate in regular check-ups

Note:

While the importance of adjuvant chemotherapy for rectal cancer after rectal resection without preoperative radiation is established, the adjuvant chemotherapy after combined radio-chemotherapy or short-term radiation and complete TME is controversially assessed. According to current teaching, adjuvant chemotherapy with optimal fluoropyrimidine schemes should be offered after neoadjuvant radio-chemotherapy. A good data basis exists here for capecitabine. The available study data currently do not allow differential therapeutic recommendations based on the degree or extent of the tumor's response to neoadjuvant radio-chemotherapy.

Younger patients with an increased risk of recurrence (yp stage III) should be counseled about the possibility of additional oxaliplatin therapy (36).

The duration of perioperative chemotherapy should add up to about 6 months, e.g., through another 5-6 cycles of adjuvant capecitabine or 8 cycles of FOLFOX.

TNT (Total Neoadjuvant Therapy):

• The present representation primarily takes the German S3 guideline as a reference point. However, it should not go unmentioned that in recent times the concept of TNT (total neoadjuvant therapy) is coming to the forefront for locally advanced rectal cancer (so-called LARC). This represents a possible alternative, especially for tumors with biologically unfavorable tumor stages and/or with intended organ preservation. Here, conventional neoadjuvant radio-chemotherapy is extended by a chemotherapy regimen usually lasting 3 to 4.5 months. This additional chemotherapy administration is possible after or before the radio- or radio-chemotherapy (as so-called induction or consolidation chemotherapy).
• The reason for this possible paradigm shift, which has already found its way into daily clinical practice at many centers, are some promising recently published study results (RAPIDO, PRODIGE-23, OPRA, CAO/ARO/AIO-12 Trial, STELLAR). Several randomized studies have shown that TNT offers a significant advantage in terms of disease-free survival, especially for patients whose tumors exhibited high-risk characteristics (e.g., criteria of the so-called RAPIDO study): 1) T4 tumors, 2) tumors with threatened/involved mesorectal resection margin, 3) EMVI positivity, 4) N2 status, and 5) enlarged lateral lymph nodes (37-41).
• The ideal design of TNT is still the subject of clinical studies. There is also a need for an internationally uniform definition of LARC (locally advanced rectal cancer).
• The following designs are possible according to the interdisciplinary recommendations of working groups of the DKG (German Cancer Society):
  • 1) Radiation therapy can be performed as short-term radiation (5x5 Gy) or long-term radio-chemotherapy.
  • 2) Chemotherapy should be administered over 3 to 4.5 months, with data from the CAO/ARO/AIO-12 and OPRA studies suggesting that consolidation chemotherapy should be preferred if the therapeutic goal is to achieve the highest possible rate of clinical complete remissions (cCR). Chemotherapy should be conducted with FOLFOX or CapOx; the benefit of an additional administration of irinotecan (e.g., in the FOLFIRINOX regimen) is not proven.

Metastatic situation

In the metastatic situation, a fundamental distinction should be made between patients with synchronous and metachronous metastasis (42-44). The synchronous must be considered prognostically unfavorable compared to the metachronous metastasis. Furthermore, information on disease dynamics is lacking here. The benefit of primary resection is therefore more uncertain in this patient group than in patients with metachronous metastasis. Other prognostic factors that can be considered in decision-making include the number of metastatic lesions, the presence of extrahepatic metastasis (45).

Patients in good general condition can be subjected to intensive treatment, i.e., surgery or chemotherapy. In cases of resectable tumor manifestations and favorable risk constellation, primary metastasis resection should be pursued. Those patients for whom primary surgical intervention is not possible should receive the most effective systemic chemotherapy possible. The primary therapeutic goal is maximum tumor reduction. The choice of chemotherapy regimen depends significantly on the molecular pathological profile of the tumor. In patients with RAS wild-type tumors, the localization of the primary tumor is added as another decision-making basis.

However, simultaneous liver metastasis resection can lead to higher mortality in patients with corresponding comorbidities or older age (>70 years). Especially in cases of multiple synchronous liver metastases, a two-stage and multimodal approach should be chosen (3).

The assessment should be made by a tumor board involving a surgeon experienced in metastatic surgery. In the case of extensive hepatic filiation in stage IV and an asymptomatic primary tumor without stenosis and without bleeding, chemotherapy can also be started without resection of the primary tumor (3).

Resection of liver metastases:

The resection of metastases is a central component of the curative concept. The following conditions should be met for an operative approach:

• Exclusion of non-resectable, extrahepatic metastases
• > 30% functional, residual liver tissue postoperatively
• sufficient safety margin from critical liver vessels
• no hepatic insufficiency, no liver cirrhosis Child B or C
• ECOG 0 – 2
• no severe comorbidity

Decisions regarding the resectability of liver metastases should always be made within the framework of interdisciplinary tumor conferences.

The standard for local therapy of liver metastases is open surgical resection with or without perioperative medication tumor therapy. Previous data show that laparoscopic resection reduces morbidity but has no impact on 90-day mortality. Less invasive ablative procedures such as radiofrequency ablation, laser therapy, or stereotactic radiation are available as alternatives. For these treatment forms, there are only very few data on overall survival. Comparative, randomized studies on the oncological equivalence of these therapeutic approaches do not exist. They are generally recommended within clinical studies for curative concepts.

Resection of lung metastases

Isolated lung metastases are rarer. The following conditions should be met for an operative approach:

• Exclusion of non-resectable, extrapulmonary metastases
• R0 resection possible
• sufficient pulmonary residual volume postoperatively
• ECOG 0 – 2
• no severe comorbidity

Decisions regarding the resectability of lung metastases are the responsibility of interdisciplinary tumor conferences.

The standard for local therapy of lung metastases was open surgical resection. An alternative is minimally invasive resections using video-assisted thoracoscopy (where the intraoperative exclusion of occult lung metastases should be critically evaluated) or radiotherapeutic procedures (such as SBRT).

Peritoneal carcinomatosis

If isolated and limited peritoneal carcinomatosis is present in colorectal cancer, the indication for cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (HIPEC) can be reviewed. The use of this combination therapy has shown a significant survival advantage in terms of extending the median survival from 12.6 to 22.3 months (50).

To determine the extent of peritoneal carcinomatosis, the Peritoneal Cancer Index (PCI) is used. The following prerequisites should be met:

• PCI<20
• No extra-abdominal metastases
• Possibility of macroscopic resection or destruction of all tumor manifestations

If the PCI value is below 20 in patients without additional extra-abdominal metastases, and if an R0 resection is possible, cytoreductive surgery with HIPEC can be performed in specialized centers. Here, the procedure should preferably be carried out within the framework of studies (3).

Perioperative concept

The ERAS concept ("enhanced recovery after surgery") of multimodal postoperative rehabilitation in gastrointestinal surgery is implemented in most clinics in this country in a partially modified form. The goal of the concept is to quickly manage the pathophysiological changes caused by the surgical procedure, such as fatigue, bowel atony, and insulin resistance. The concept includes, among other things, the early removal of gastric tubes and intra-abdominal drains, early oral diet initiation, stimulation of bowel motility, sufficient analgesia (epidural/peridural), and early mobilization. Numerous studies have shown that the ERAS concept can achieve a significant reduction in length of stay, a reduction in perioperative morbidity, and an acceleration of recovery (51, 52).

(2021-2023, chronologically backwards)

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• Leitao MM Jr, Kreaden US, Laudone V, Park BJ, Pappou EP, Davis JW, Rice DC, Chang GJ, Rossi EC, Hebert AE, Slee A, Gonen M The RECOURSE Study: Long-term Oncologic Outcomes Associated With Robotically Assisted Minimally Invasive Procedures for Endometrial, Cervical, Colorectal, Lung, or Prostate Cancer: A Systematic Review and Meta-analysis. Ann Surg. 2023 Mar 1;277(3):387-396. doi: 10.1097/SLA.0000000000005698. Epub 2022 Sep 8.PMID: 36073772
• Crolla RMPH, Coffey JC, Consten EJC The Mesentery in Robot-Assisted Total Mesorectal Excision.Clin Colon Rectal Surg. 2022 Aug 10;35(4):298-305. doi: 10.1055/s-0042-1743583. eCollection 2022 Jul.PMID: 35975108 Review.
• Abbass MA. Research Perspective on Patient-Related Functional Outcomes After Robotic-Assisted Rectal Surgery Compared With a Laparoscopic Approach: A Systematic Review and Meta-analysis.Dis Colon Rectum. 2022 Oct 1;65(10):1205. doi: 10.1097/DCR.0000000000002572. Epub 2022 Sep 8.
• Ryu HS, Kim J .Current status and role of robotic approach in patients with low-lying rectalcancer.Ann Surg Treat Res. 2022 Jul;103(1):1-11. doi: 10.4174/astr.2022.103.1.1. Epub 2022 Jul 7.PMID: 35919115 Free PMC article. Review.
• Flynn J, Larach JT, Kong JCH, Waters PS, McCormick JJ, Warrier SK, Heriot A. Patient-Related Functional Outcomes After Robotic-Assisted Rectal SurgeryCompared With a Laparoscopic Approach: A Systematic Review and Meta-analysis.Dis Colon Rectum. 2022 Oct 1;65(10):1191-1204. doi: 10.1097/DCR.0000000000002535. Epub 2022 Jul 15.PMID: 35853177
• Yamauchi S, Hanaoka M, Iwata N, Masuda T, Tokunaga M, Kinugasa Y Robotic-assisted Surgery: Expanding Indication to Colon Cancer in Japan. .J Anus Rectum Colon. 2022 Apr 27;6(2):77-82. doi: 10.23922/jarc.2021-073. eCollection 2022.PMID: 35572487 Free PMC article. Review.
• Liu G, Zhang S, Zhang Y, Fu X, Liu X. Robotic Surgery in Rectal Cancer: Potential, Challenges, and Opportunities. Curr Treat Options Oncol. 2022 Jul;23(7):961-979. doi: 10.1007/s11864-022-00984-y. Epub 2022 Apr 18.PMID: 35438444 Free PMC article. Review.
• Lam J, Tam MS, Retting RL, McLemore EC. Robotic Versus Laparoscopic Surgery for Rectal Cancer: A Comprehensive Review of Oncological Outcomes. Perm J. 2021 Dec 14;25:21.050. doi: 10.7812/TPP/21.050.PMID: 35348098 Free PMC article. Review
• Safiejko K, Tarkowski R, Koselak M, Juchimiuk M, Tarasik A, Pruc M, Smereka J, Szarpak L .Robotic-Assisted vs. Standard Laparoscopic Surgery for Rectal CancerResection: A Systematic Review and Meta-Analysis of 19,731 Patients.Cancers (Basel). 2021 Dec 30;14(1):180. doi: 10.3390/cancers14010180.PMID: 35008344 Free PMC article. Review.
• Zhang J, Qi X, Yi F, Cao R, Gao G, Zhang C. Comparison of Clinical Efficacy and Safety Between da Vinci Robotic and Laparoscopic Intersphincteric Resection for Low Rectal Cancer: A Meta-Analysis.Front Surg. 2021 Dec 2;8:752009. doi: 10.3389/fsurg.2021.752009. eCollection 2021.PMID: 34926566 Free PMC article.
• Piozzi GN, Kim SH. Robotic Intersphincteric Resection for Low Rectal Cancer: Technical Controversies and a Systematic Review on the Perioperative, Oncological, and Functional Outcomes.Ann Coloproctol. 2021 Dec;37(6):351-367. doi: 10.3393/ac.2021.00836.0119. Epub 2021 Nov 17.PMID: 34784706 Free PMC article. Review.
• Tong G, Zhang G, Zheng Z. Robotic and robotic-assisted vs Laparoscopic rectal cancer surgery: A meta-analysis of short-term and long-term results.Asian J Surg. 2021 Dec;44(12):1549. doi: 10.1016/j.asjsur.2021.08.053. Epub 2021 Sep 27.PMID: 34593279 Free article. No abstract available
• Butterworth JW, Butterworth WA, Meyer J, Giacobino C, Buchs N, Ris F, Scarpinata R.A systematic review and meta-analysis of robotic-assisted transabdominal total mesorectal excision and transanal total mesorectal excision: which approach offers optimal short-term outcomes for mid-to-low rectal adenocarcinoma? Tech Coloproctol. 2021 Nov;25(11):1183-1198. doi: 10.1007/s10151-021-02515-7. Epub 2021 Sep 25.PMID: 34562160 Review.
• Chen MZ, Tay YK, Warrier SK, Heriot AG, Kong JC. Robotic total mesorectal excision or transanal total mesorectal excision meta-analysis.ANZ J Surg. 2021 Nov;91(11):2269-2276. doi: 10.1111/ans.17204. Epub 2021 Sep 23.PMID: 34553466 Review.
• Quezada-Diaz FF, Smith JJ. Options for Low Rectal Cancer: Robotic Total Mesorectal Excision.Clin Colon Rectal Surg. 2021 Sep;34(5):311-316. doi: 10.1055/s-0041-1726449. Epub 2021 Sep 8.PMID: 34512198 Free PMC article. Review.
• Grass JK, Chen CC, Melling N, Lingala B, Kemper M, Scognamiglio P, Persiani R, Tirelli F, Caricato M, Capolupo GT, Izbicki JR, Perez DR. Robotic rectal resection preserves anorectal function: Systematic review and meta-analysis.Int J Med Robot. 2021 Dec;17(6):e2329. doi: 10.1002/rcs.2329. Epub 2021 Sep 9.PMID: 34463416 Review.
• Wang X, Zheng Z, Yu Q, Ghareeb WM, Lu X, Huang Y, Huang S, Lin S, Chi P. Impact of Surgical Approach on Surgical Resection Quality in Mid- and Low Rectal Cancer, A Bayesian Network Meta-Analysis.Front Oncol. 2021 Aug 11;11:699200. doi: 10.3389/fonc.2021.699200. eCollection 2021.PMID: 34458142 Free PMC article.
• Mann B, Kukies S, Krogh O, Virakas G.[Robotic-assisted surgery of rectal cancer-Technique, limitations and results].Chirurg. 2021 Jul;92(7):599-604. doi: 10.1007/s00104-021-01424-7. Epub 2021 May 18.PMID: 34003314 Review. German.
• Baek SJ, Piozzi GN, Kim SH. Optimizing outcomes of colorectal cancer surgery with robotic platforms. Surg Oncol. 2021 Jun;37:101559. doi: 10.1016/j.suronc.2021.101559. Epub 2021 Mar 31.PMID: 33839441 Review.
• Tang B, Lei X, Ai J, Huang Z, Shi J, Li T. Comparison of robotic and laparoscopic rectal cancer surgery: a meta-analysis of randomized controlled trials.World J Surg Oncol. 2021 Feb 3;19(1):38. doi: 10.1186/s12957-021-02128-2.PMID: 33536032 Free PMC article.
• Guo Y, Guo Y, Luo Y, Song X, Zhao H, Li L. Comparison of pathologic outcomes of robotic and open resections for rectalcancer: A systematic review and meta-analysis.PLoS One. 2021 Jan 13;16(1):e0245154. doi: 10.1371/journal.pone.0245154. eCollection 2021.PMID: 33439912 Free PMC article.

German Guidelines

S3 Guideline Colorectal Carcinoma (Guideline Program Oncology (German Cancer Society, German Cancer Aid, AWMF): S3 Guideline Colorectal Carcinoma. Valid until 29.11.2022): https://www.awmf.org/uploads/tx_szleitlinien/021-007OLl_S3_Kolorektales-Karzinom-KRK_2019-01.pdf

International Guidelines

European Society for Medical Oncology (ESMO):

Glynne-Jones R, Wyrwicz L, Tiret E, Brown G, Rödel C, Cervantes A, Arnold D (2017) Rectal cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. https://doi.org/10.1093/annonc/mdx224

Management of Patients with Metastatic Colorectal Cancer 2016

Metastatic Colorectal Cancer 2014

Management of Patients with Colon and Rectal Cancer. A personalized approach to clinical decision making

National Comprehensive Cancer Network (NCCN)

Benson AB, Venook AP, Al-Hawary MM, Cederquist L, Chen Y‑J, Ciombor KK, Cohen S, Cooper HS, Deming D, Engstrom PF et al (2018) Rectal cancer, version 2.2018, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. https://doi.org/10.6004/jnccn.2018.0061

American Society of Colon and Rectal Surgeons (ASCRS):

Practice Guideline for the Surveillance of Patients After Curative Treatment of Colon and Rectal Cancer