Step 1 (evaluation of individual study): study design, evaluation of bias risk, create structured abstract |
Step 2 (overall rating for each important outcome across studies) |
1. Initial quality of a body of evidence: evaluation of each study design group |
systematic reviews, meta-analysis, randomized controlled trials = “initial quality A (high level)” |
observation studies, cohort studies, case control studies = “initial quality C (low level)” |
case series, case reports = “initial quality D (very low level)” |
2. Five reasons to possibility rate down the quality |
risk of bias |
inconsistency in results |
indirectness of evidence |
data imprecision |
high possibility of publication bias |
3. Three reasons to possibility rate up the quality |
large effect with no confounding factors |
dose–response gradient |
possible confounding factors are weaker than actual effects |
4. We evaluate 1 → 2 → 3, and assess the quality of a body of evidence |
A (high) | We are very confident in the effect estimate |
B (moderate) | We are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different |
C (low) | Our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect |
D (very low) | We have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect |
Strength of recommendation | |
1 (Strong recommendation) | Strong “For” an intervention |
Strong “Against” an intervention | |
2 (Weak recommendation) | Weak “For” an intervention |
Weak “Against” an intervention |
Number of articles retrieved | Number of articles selected | Number of articles retrieved manually | |||
---|---|---|---|---|---|
PubMed | Ichushi | PubMed | Ichushi | ||
(1) Endoscopic treatment of colorectal cancer | 811 | 385 | 80 | 40 | 39 |
(2) Treatment of Stage 0 to Stage III colorectal cancer | 469 | 285 | 92 | 14 | 12 |
(3) Treatment of Stage IV colorectal cancer | 237 | 102 | 97 | 14 | 13 |
(4) Treatment of liver metastases of colorectal cancer | 812 | 357 | 364 | 79 | 25 |
(5) Treatment of lung metastases of colorectal cancer | 96 | 157 | 46 | 35 | 6 |
(6) Treatment of recurrent colorectal cancer | 688 | 302 | 147 | 29 | 13 |
(7) Adjuvant chemotherapy for colorectal cancer | 855 | 450 | 244 | 39 | 47 |
(8) Chemotherapy for advanced or recurrent colorectal cancer | 1062 | 451 | 320 | 53 | 157 |
(9) Adjuvant radiotherapy for colorectal cancer | 447 | 95 | 115 | 8 | 27 |
(10) Palliative radiotherapy for colorectal cancer | 708 | 39 | 109 | 6 | 29 |
(11) Palliative care for colorectal cancer | 278 | 181 | 58 | 18 | 10 |
(12) Surveillance after surgery for colorectal cancer | 1446 | 1287 | 256 | 57 | 20 |
Total | 7909 | 4091 | 1928 | 392 | 398 |
-
There is little possibility of lymph node metastasis, and the size and location of the tumor make en bloc resection possible.
-
Endoscopic treatment is a method of endoscopically resecting lesions in the large bowel and of collecting the resected specimens.
-
Endoscopic treatment methods consist of polypectomy (note 1), endoscopic mucosal resection (EMR) (note 2), and endoscopic submucosal dissection (ESD) (note 3).
-
In determining the indication for endoscopic treatment and the treatment method, information on the size, predicted depth of invasion, and morphology of the tumor is essential.
-
2 cm is the largest size of a tumor that can be easily resected en bloc by polypectomy or snare EMR [27]. (CQ-2)
-
Colorectal ESD is an “endoscopic resection technique which enables en bloc resection of a tumor, regardless of size,” which was approved for implementation under health insurance in April 2014 in regard to “early-stage malignant tumors” Given the high likelihood of technically difficult complications (perforations); however, it should only be implemented after sufficient consideration of the level of skill of the endoscopist performing the procedure. At present, tumors with a diameter between 2-5 cm are covered by insurance (CQ-3).
-
EMRC (EMR using a cap) is reported to involve a high risk of perforation when used for colon lesions.
-
If the preoperative diagnosis is cancer accompanied by adenoma (intramucosal carcinoma), a piecemeal resection can be performed in regard to the adenoma, while avoiding division of the cancerous area. It should be noted, however, that piecemeal resection is associated with a high incomplete resection rate and a high local recurrence rate [27].
-
The extent of lymph node dissection to be performed during colorectal cancer surgery is determined based on the preoperative clinical findings and on the extent of lymph node metastasis and depth of tumor invasion by the tumor observed intraoperatively.
-
If lymph node metastasis is recognized, or suspected based on the preoperative/intraoperative findings, D3 dissection is performed.
-
If no lymph node metastases are observed based on the preoperative/intraoperative diagnostic findings, lymph node dissection is performed based on the depth of tumor invasion [29].
No. of patients | No. of patients who underwent lateral dissection | Lateral dissection rate | No. of patients with lateral metastasis | Lateral metastasis rate (percentage of all patients) | Lateral metastasis rate (percentage of patients who underwent lateral dissection) | |
---|---|---|---|---|---|---|
RS | ||||||
sm | 124 | 0 | 0 | 0 | 0.0 | 0.0 |
mp | 127 | 6 | 4.7% | 0 | 0.0 | 0.0 |
ss/a1
| 316 | 24 | 7.5% | 0 | 0.0 | 0.0 |
se/a2
| 177 | 8 | 4.5% | 0 | 0.0 | 0.0 |
si/ai | 32 | 14 | 43.8% | 1 | 3.1 | 7.1 |
Total | 776 | 52 | 6.7% | 1 | 0.1 | 1.9 |
Ra | ||||||
sm | 138 | 5 | 3.6% | 0 | 0.0 | 0.0 |
mp | 149 | 18 | 12.1% | 0 | 0.0 | 0.0 |
ss/a1
| 230 | 58 | 25.2% | 4 | 1.7 | 6.9 |
se/a2
| 181 | 59 | 32.6% | 7 | 3.9 | 11.9 |
si/ai | 15 | 8 | 53.3% | 0 | 0.0 | 0.0 |
Total | 713 | 148 | 20.8% | 11 | 1.5 | 7.4 |
RaRb + Rb | ||||||
sm | 234 | 37 | 15.8% | 2 | 0.9 | 5.4 |
mp | 372 | 218 | 58.6% | 20 | 5.4 | 9.2 |
ss/a1
| 350 | 230 | 65.7% | 28 | 7.7 | 12.2 |
se/a2
| 412 | 319 | 77.4% | 75 | 18.0 | 23.5 |
si/ai | 59 | 48 | 81.4% | 17 | 28.8 | 35.4 |
Total | 1427 | 852 | 59.7% | 142 | 9.8 | 16.7 |
-
Lateral lymph node dissection is indicated when the lower border of the tumor is located distal to the peritoneal reflection and the tumor has invaded beyond the muscularis propria [30].
-
Local excision is indicated for cTis (M) cancer and cT1 (SM) cancer (slight invasion) located distal to the second Houston valve (peritoneal reflection).
-
Histological investigation of the resected specimen allows a determination to be made of the likelihood that treatment will cure the condition completely, along with the need for additional treatment (intestinal resection accompanied by lymph node dissection).
-
The autonomic nervous system related to surgery for rectal cancer consists of the lumbar splanchnic nerves, superior hypogastric plexus, hypogastric nerves, pelvic splanchnic nerves, and pelvic plexus. Considering factors such as the degree of cancer progression and presence or absence of macroscopic nerve invasion, preservation of autonomic nerves is attempted in order to preserve urinary and sexual functions as much as possible, provided that curability is unaffected.
-
The indications for laparoscopic surgery are determined by considering the surgeon’s experience and skills, as well as tumor factors, such as the location and degree of progression of the cancer, and patient factors, such as obesity and history of open abdominal surgery. (CQ-4)
No. of patients | Extent of lymph node metastasis detected histologically | |||||
---|---|---|---|---|---|---|
n
0 (%) |
n
1 (%) |
n
2 (%) |
n
3 (%) |
n
4 (%) | ||
All sites | ||||||
sm | 3151 | 90.7 | 7.3 | 1.9 | 0.0 | 0.1 |
mp | 3590 | 77.3 | 17.4 | 4.2 | 0.9 | 0.3 |
ss/a1
| 11,272 | 54.6 | 29.9 | 12.0 | 2.3 | 1.2 |
se/a2
| 6101 | 35.9 | 34.4 | 20.2 | 5.7 | 3.8 |
si/ai | 1502 | 43.0 | 27.6 | 16.4 | 6.7 | 6.3 |
Total | 25,617 | 57.1 | 26.3 | 11.9 | 2.9 | 1.9 |
Colon | ||||||
sm | 1957 | 91.4 | 6.8 | 1.8 | 0.0 | 0.0 |
mp | 1747 | 79.3 | 16.3 | 3.5 | 0.6 | 0.3 |
ss/a1
| 7333 | 56.6 | 28.1 | 11.7 | 2.4 | 1.2 |
se/a2
| 3363 | 37.4 | 34.0 | 19.3 | 5.6 | 3.7 |
si/ai | 960 | 44.6 | 28.6 | 14.7 | 5.5 | 6.6 |
Total | 15,360 | 58.6 | 25.4 | 11.3 | 2.8 | 1.8 |
Rectosigmoid | ||||||
sm | 337 | 88.7 | 9.5 | 1.8 | 0.0 | 0.0 |
mp | 429 | 80.4 | 17.0 | 2.6 | 0.0 | 0.0 |
ss/a1
| 1584 | 53.9 | 33.0 | 10.2 | 1.3 | 1.7 |
se/a2
| 789 | 34.2 | 38.4 | 20.8 | 3.2 | 3.4 |
si/ai | 187 | 44.9 | 24.6 | 19.3 | 4.8 | 6.4 |
Total | 3326 | 55.7 | 29.3 | 11.4 | 1.6 | 2.0 |
Rectum | ||||||
sm | 839 | 89.7 | 7.7 | 2.0 | 0.1 | 0.4 |
mp | 1373 | 73.9 | 19.2 | 5.4 | 1.4 | 0.1 |
ss/a1
| 2310 | 48.8 | 33.3 | 14.2 | 2.7 | 1.0 |
se/a2
| 1904 | 33.9 | 33.6 | 21.5 | 6.8 | 4.1 |
si/ai | 328 | 38.1 | 26.2 | 19.8 | 10.4 | 5.5 |
Total | 6754 | 54.3 | 27.0 | 13.3 | 3.6 | 1.8 |
Anal canal | ||||||
sm | 18 | 94.4 | 0.0 | 5.6 | 0.0 | 0.0 |
mp | 41 | 70.7 | 9.8 | 7.3 | 7.3 | 4.9 |
ss/a1
| 45 | 60.0 | 22.2 | 8.9 | 6.7 | 2.2 |
se/a2
| 46 | 32.6 | 21.7 | 23.9 | 15.2 | 6.5 |
si/ai | 27 | 33.3 | 25.9 | 14.8 | 18.5 | 7.4 |
Total | 177 | 54.8 | 17.5 | 13.0 | 10.2 | 4.5 |
Stage | I | II | IIIa | IIIb | IV | All Stages |
---|---|---|---|---|---|---|
All patients | 98.7% | 96.2% | 91.9% | 81.8% | – | 78.0% |
5455 | 7336 | 5635 | 2572 | 4300 | 25,298 | |
Colon | 99.1% | 96.6% | 92.4% | 83.6% | – | 77.2% |
3028 | 4688 | 3208 | 1379 | 2787 | 15,090 | |
Rectosigmoid | 99.5% | 96.6% | 92.5% | 80.2% | – | 78.0% |
615 | 961 | 835 | 288 | 560 | 3259 | |
Rectum | 97.9% | 95.0% | 90.9% | 80.5% | – | 79.9% |
1764 | 1644 | 1564 | 866 | 929 | 6767 | |
Anal canal | 95.8% | 86.0% | 78.6% | 61.5% | – | 70.9% |
48 | 43 | 28 | 39 | 24 | 182 |
Stage | 0 | I | II | IIIa | IIIb | IV | All Stages |
---|---|---|---|---|---|---|---|
Cecum | 91.0% | 93.7% | 83.5% | 73.0% | 65.4% | 12.5% | 68.2% |
79 | 185 | 249 | 207 | 113 | 204 | 1037 | |
Ascending colon | 93.9% | 91.2% | 85.8% | 79.1% | 63.4% | 19.1% | 71.4% |
125 | 338 | 656 | 416 | 211 | 410 | 2156 | |
Transverse colon | 88.9% | 91.4% | 85.2% | 78.5% | 65.7% | 20.8% | 74.0% |
105 | 277 | 428 | 244 | 138 | 210 | 1402 | |
Descending colon | 100.0% | 94.1% | 85.3% | 82.0% | 52.9% | 21.1% | 75.4% |
43 | 146 | 224 | 166 | 52 | 117 | 748 | |
Sigmoid colon | 94.2% | 92.3% | 85.8% | 83.0% | 64.7% | 22.0% | 73.7% |
154 | 852 | 1124 | 837 | 363 | 736 | 4066 | |
Rectosigmoid | 89.4% | 91.5% | 84.8% | 78.0% | 60.0% | 19.8% | 71.6% |
54 | 366 | 539 | 473 | 175 | 322 | 1929 | |
Upper rectum | 98.0% | 95.3% | 84.6% | 75.9% | 57.7% | 11.6% | 72.4% |
67 | 356 | 464 | 471 | 173 | 263 | 1794 | |
Lower rectum | 97.5% | 88.3% | 81.7% | 70.0% | 51.4% | 11.6% | 70.5% |
142 | 718 | 486 | 473 | 332 | 298 | 2449 | |
Anal canal | 100.0% | 78.7% | 90.9% | 46.9% | 61.2% | 15.7% | 60.0% |
4 | 16 | 14 | 16 | 19 | 17 | 86 | |
Colon | 93.0% | 92.3% | 85.4% | 80.4% | 63.8% | 19.9% | 72.8% |
506 | 1798 | 2681 | 1870 | 877 | 1677 | 9409 | |
Rectum | 97.6% | 90.6% | 83.1% | 73.0% | 53.5% | 14.8% | 71.3% |
209 | 1074 | 950 | 944 | 505 | 561 | 4243 | |
All sites | 94.0% | 91.6% | 84.8% | 77.7% | 60.0% | 18.8% | 72.1% |
773 | 3254 | 4184 | 3303 | 1576 | 2577 | 15,667 |
-
Stage IV colorectal cancer is associated with synchronous distant metastasis to any of the following organs: liver, lung, peritoneum, brain, distant lymph nodes, or other organ (e.g., bone, adrenal gland, spleen).
-
If both the distant metastases and the primary tumor are resectable, curative resection of the primary tumor is performed, and resection of the distant metastases is considered.
-
If the distant metastases are resectable, but the primary tumor is unresectable, in principle, resection of the primary tumor and distant metastases is not performed, and another treatment method is selected.
-
If the distant metastases are unresectable, but the primary tumor is resectable, the indication for the resection of the primary tumor is determined, based on the clinical symptoms of the primary tumor and the impact on the prognosis (CQ-4).
Liver | Lung | Peritoneum | Other sites | |||||
---|---|---|---|---|---|---|---|---|
Bone | Brain | Virchow | Other | Total | ||||
Colon cancer | 11.8% | 2.2% | 5.7% | 0.3% | 0.0% | 0.1% | 1.3% | 1.8% |
No. of patients 15,391 | 1815 | 338 | 875 | 47 | 6 | 23 | 205 | 281 |
Rectal cancer | 9.5% | 2.7% | 2.6% | 0.5% | 0.0% | 0.1% | 1.1% | 1.7% |
No. of patients 10,221 | 970 | 273 | 266 | 49 | 5 | 6 | 112 | 172 |
Total no. of patients | 10.9% | 2.4% | 4.5% | 0.4% | 0.0% | 0.1% | 1.2% | 1.8% |
2785 | 611 | 1141 | 96 | 11 | 29 | 317 | 453 |
-
Complete resection is desirable for P1.
-
Complete resection is considered for P2 when easily resectable.
-
The efficacy of resection of P3 has not been demonstrated.
-
The efficacy and safety of adjuvant chemotherapy following the resection of distant metastasis in colorectal cancer have not been established, and no randomized controlled trials have been implemented regarding whether or not it extends survival [37, 38]. (CQ-8) Ideally, appropriately planned clinical trials should be implemented.
-
The goal of treatment for recurrent colorectal cancer is improvement of the prognosis and patient’s QOL.
-
Treatment methods include surgery, systemic chemotherapy, arterial infusion chemotherapy, thermal coagulation therapy, and radiotherapy.
-
An appropriate treatment method is selected with the informed consent of the patient in view of a variety of factors, such as the prognosis, complications, and QOL expected after treatment.
-
If recurrence is observed in a single organ and complete surgical resection of the recurrent tumor(s) is possible, resection is strongly considered.
-
Some authors believe that resection of liver or lung metastases should be performed only after a certain observation period to rule out occult metastases [40].
-
Treatment methods for hematogenous metastases (see chapter 4 “Treatment strategies for hematogenous metastases”)
-
Local recurrences of rectal cancer take the form of anastomotic recurrences and intrapelvic recurrences.
-
Treatment of liver metastases is broadly divided into hepatectomy, systemic chemotherapy, hepatic arterial infusion therapy, and thermal coagulation therapy.
-
Hepatectomy is recommended for liver metastases when curative resection is possible.
-
Hepatectomy consists of systematic resection and partial (non-systematic) resection.
-
Indication criteria for hepatectomy
-
Systemic chemotherapy is considered for patients with unresectable liver metastases whose general condition can be maintained at a certain level or higher (PS 0 to PS 2).
-
Thermal coagulation therapy consists of microwave coagulation therapy (MCT) and radiofrequency ablation (RFA).
-
If the patient’s general condition is poor (PS ≥3), or there is no effective chemotherapy, best supportive care (BSC) is provided.
-
Treatment of lung metastases consists of pneumonectomy and systemic chemotherapy, and radiotherapy.
-
Pneumonectomy is considered if the metastatic lung tumor is resectable.
-
Pneumonectomy consists of systematic resection and partial (non-systematic) resection.
-
Systemic chemotherapy is considered for patients with unresectable lung metastases whose general condition can be maintained at a certain level or higher.
-
Even if the patient cannot tolerate surgery, stereotactic body radiotherapy is considered if the primary tumor and extrapulmonary metastases are controlled or can be controlled and the number of lung metastases within 5 cm in diameter is no more than three [48].
-
If the patient’s general condition is poor, appropriate BSC is provided.
-
Brain metastases are often detected as a part of a systemic disease, and surgical therapy or radiotherapy is considered for lesions in which treatment can be expected to be effective.
-
The optimal treatment method is selected after considering the patient’s general condition and status of other metastatic tumors, and evaluating the size and location of metastatic brain tumors and the number of brain lesions.
-
Radiotherapy is considered for patients with unresectable metastases.
-
The purpose of radiotherapy is to relieve symptoms, such as cranial nerve symptoms and intracranial hypertension symptoms, and to prolong survival time by reducing locoregional relapse.
-
Whole-brain radiotherapy is considered for patients with multiple brain metastases and for patients with a solitary brain metastasis for which surgical resection is not indicated.
-
Stereotactic irradiation is considered when the number of brain metastases is about no more than three or four and the maximum diameter of each metastasis does not exceed 3 cm.
-
Resection is also considered for other hematogenous metastases, such as to the adrenal glands, skin, and spleen, if they are resectable. However, patients with such metastases often have metastasis to more than one organ, and chemotherapy or radiotherapy is often indicated.
-
Chemotherapy consists of adjuvant chemotherapy to prevent postoperative recurrence and systemic chemotherapy to treat unresectable colorectal cancer.
-
Commonly used anticancer drugs that have been approved for the indication of colorectal cancer and are covered by the Japanese National Health Insurance include the following:
-
Postoperative adjuvant chemotherapy is a systemic chemotherapy that is performed after surgery to prevent recurrence and improve the prognosis of patients who have undergone R0 resection [50].
-
Bone marrow: Peripheral blood neutrophil count >1500/mm3; platelet count >100,000/mm3
-
Liver function: Total bilirubin <2.0 mg/dL; AST/ALT <100 IU/L
-
Renal function: Serum creatinine concentration is no higher than the upper limit of the normal range at the institution.
-
5-FU + l-LV (note)
-
UFT + LV
-
Cape
-
FOLFOX
-
CapeOX
-
S-1
-
In principle, the administration period is 6 months.
-
In the best supportive care (BSC) without any chemotherapy, the median survival time (MST) of patients with unresectable colorectal cancer has been reported to be approximately 8 months. Although their MST has been extended to approximately 30 months because of recent chemotherapy, unresectable colorectal cancer remains difficult to cure.
-
The purpose of chemotherapy is to prolong survival time and control symptoms by delaying tumour enlargement.
-
Initially unresectable colorectal cancer may become resectable after successful chemotherapy.
-
Patients should be ideally divided into two groups and their treatment policy selected according to whether or not they are appropriate for intensive therapy.
-
Patients appropriate for intensive therapy include those with no serious comorbidities who are considered tolerant to primary treatment with OX and IRI, as well as concomitant therapy with molecular target drugs. These patients, who have considerably slow tumour advancement and have preferably not suffered severe adverse events can be treated with either monotherapy or doublet therapy as the primary treatment.
-
Patients inappropriate for intensive therapy include those with serious comorbidities who are considered intolerant to primary treatment with OX and IRI, as well as concomitant therapy with molecular target drugs. For these patients, monotherapy or doublet therapy shall be considered as the primary treatment.
-
Cmab and Pmab are only used in response to wild-type RAS(KRAS/NRAS).
-
Combination with molecular target drugs, such as Bmab, anti-EGFR antibodies, or Rmab, is recommended, but for patients who are not candidates, chemotherapy alone is administered.
-
The following are regimens whose usefulness has been demonstrated in clinical trials. They are also available as the initial therapy covered by the Japanese National Health Insurance.
-
The following regimens are considered as chemotherapy for second-line therapy (CQ-16).
-
Radiotherapy is used to treat patients with locally advanced rectal cancer either as adjuvant therapy after surgery to prevent recurrence or before surgery to reduce tumor volume and preserve the anal sphincter, and also as palliative care to relieve the symptoms and prolong the survival time of patients with unresectable colorectal cancer who have symptomatic lesions.
-
Adjuvant radiotherapy is classified into three categories, according to the timing of surgery and radiation therapy: preoperative radiotherapy, intraoperative radiotherapy, and postoperative radiotherapy.
-
The purpose of adjuvant radiotherapy is to improve the local control rate and the survival rate of rectal cancer patients. The purpose of preoperative radiotherapy includes improving the anal sphincter preservation rate and improving the resection rate. However, insufficient evidence of improved survival has been found to make this the objective of adjuvant radiotherapy.
-
Preoperative radiotherapy is indicated for patients with T stage clinically diagnosed as “invasion depth cT3 (SS/A) or deeper or cN-positive”; postoperative radiotherapy is indicated for patients with T stage pathologically diagnosed after surgery as “invasion depth cT3 (SS/A) or deeper or pN-positive, where the existence of a surgical dissection plane positive (RM1) or penetration of the surgical dissection plane by the cancer (RMX) is unclear”; and intraoperative radiotherapy is indicated for “surgical dissection plane positive (RM1) or penetration of the surgical dissection plane by the cancer (RMX) is unclear”.
-
Radiotherapy is delivered with a linear accelerator, where electron beams are used for intraoperative radiotherapy and photon beams for external radiotherapy.
-
The purpose of palliative radiotherapy for intrapelvic lesions is to relieve symptoms such as pain, hemorrhage, and bowel movement disorders caused by intrapelvic tumors.
-
The target volume includes the tumor that is causing the symptoms.
-
A total dose of 45 Gy to 50 Gy is administered in 1.8–2.0 Gy fractions.
-
Depending on the patient’s general condition, such as performance status, and the severity of the symptoms, radiotherapy may be completed in a shorter term with a larger fraction size, for example 30 Gy in 10 fractions over 2 weeks.
-
The purpose of palliative radiotherapy for bone metastases is to achieve pain relief, prevent pathological fractures, and prevent and treat spinal cord paralysis.
-
The target volume includes the metastatic bone lesions causing the symptoms.
-
Local field radiotherapy, such as 30 Gy in 10 fractions and 20 Gy in five fractions, is widely performed.
-
See the section on hematogenous metastases (Chapter 4).
-
When whole brain radiotherapy is performed, 30 Gy in 10 fractions is the standard treatment. If long-term survival is expected, fractionated radiotherapy, such as 37.5 Gy in 15 fractions and 40 Gy in 20 fractions, is considered.
-
When stereotactic radiosurgery is performed, a peripheral dose of 16 Gy to 25 Gy is delivered in a single fraction.
-
Palliative care is a general term for palliative treatment of various mental and physical symptoms related to cancer.
-
Palliative care extends from the time the diagnosis of cancer is made to the end stage, and different care should be provided depending on the disease stage and symptoms.
-
In principle, cancer treatment should be performed under conditions in which symptom relief is achieved [126], and palliative care should be started at the same time as surgical treatment and chemotherapy.
-
Palliative care to improve the QOL of patients with end-stage colorectal cancer includes:
-
In principle, the duration of surveillance is 5 years after surgery, but the surveillance examinations should be scheduled at shorter intervals during the first 3 years after surgery.
-
It should be noted that there is a higher incidence of lung metastasis and local recurrence in rectal cancer than in colon cancer.
-
As a general rule, the duration of surveillance for anastomotic recurrence is until 3 years after surgery.
-
The following is an example of a surveillance schedule after curative resection of Stage I to Stage III colorectal cancer that was designed on the basis of the results of a retrospective investigation of such factors as the common sites and incidence of recurrence and the efficacy of treatment and the clinical practice in Japan (Fig. 7).×
-
Colonoscopy is performed for surveillance of metachronous multicentric colorectal cancer.
-
The aim of surveillance is to improve the patient’s prognosis by early detection and treatment of recurrences. Meta-analyses of RCTs conducted in Europe and the United States have shown that surveillance after curative surgical resection of colorectal cancer contributes to improving the resection rate of recurrent tumors and to improving the prognosis [127‐131] (CQ-20-1).
-
The results of the project study by the JSCCR are shown in Figs. 8, 9 and Tables 10, 11, 12, and 13. The subjects were patients who underwent curative resection of colorectal cancer between 1991 and 1996 at the 14 institutions that participated in the project, and the follow-up period was 6–11 years.Table 10Recurrence rate after curative resection of colorectal cancer according to stage and cumulative incidence of recurrence according to the number of years after surgeryStage (no. of patients)Recurrence rate (no. of patients with recurrence)Cumulative incidence of recurrence according to the no. of years after surgery (cumulative no. of patients with recurrence)Percentage of patients experiencing recurrence more than 5 years after surgery among all patients (no. of patients)3 years4 years5 yearsI3.7%68.6%82.4%96.1%0.15%(1367)(51)(35)(42)(49)(2)II13.3%76.9%88.2%92.9%0.94%(1912)(255)(196)(225)(237)(18)III30.8%87.0%93.8%97.8%0.67%(1957)(600)(522)(563)(587)(13)All17.3%83.2%91.6%96.4%0.63%(5230)(906)(753)(830)(873)(33)Table 11Recurrence rate of Stage I colorectal cancer (RS cancer was counted as colon cancer)Stage INo. of patientsNo. of patients with recurrenceRecurrence rate (%)p valueTumor locationColon891242.70.0056Rectum476275.7Depth of tumor invasionSM71491.3<0.0001MP653426.4Tumor location and depth of tumor invasionColonSM52871.30.0024MP363174.7RectumSM18621.10.0005MP290258.6Table 12Recurrence rate according to the site of the first recurrence after curative resection of colorectal cancer and cumulative incidence of recurrence according to the number of years after surgerySite of first recurrenceRecurrence rate (no. of patients with recurrence (including overlaps)Cumulative incidence of recurrence according to the number of years after surgery (cumulative no. of patients with recurrence)Percentage of patients experiencing recurrence more than 5 years after surgery among all patients (no. of patients)3 years4 years5 yearsLiver7.1% (373)87.9% (328)94.1% (351)98.7% (368)0.10% (5)Lung4.8% (250)78.0% (195)88.8% (222)94.8% (237)0.25% (13)Local4.0% (209)80.9% (169)90.4% (189)96.2% (201)0.15% (8)Anastomotic0.4% (22)95.5% (21)95.5% (21)95.5% (21)0.02% (1)Other3.8% (199)79.4% (158)91.0% (181)95.5% (190)0.17% (9)All (5230)17.3% (906)Table 13Comparison between the recurrence rates of colon cancer and rectal cancer according to the site of the first recurrence (RS cancer was counted as colon cancer)Site of recurrenceColon cancer (3583 patients)Rectal cancer (1647 patients)p valueLiver7.0% (252)7.3% (121)NSLung3.5% (126)7.5% (124)<0.0001Local1.8% (64)8.8% (145)0.0001Anastomotic0.3% (9)0.8% (13)0.0052Other3.6% (130)4.2% (69)NSAll14.1% (506)24.3% (400)<0.0001××
-
More than 80% of the recurrences were detected within 3 years after surgery, and more than 95% of the recurrences were detected within 5 years after surgery.
-
The overall incidence of recurrence more than 5 years after surgery was less than 1%.
-
Among lung recurrences, 5% of recurrences were detected more than 5 years after surgery.
-
More than 95% of the anastomotic recurrences were detected within 3 years after surgery.
-
Local recurrence and lung recurrence were more frequent in rectal cancer than in colon cancer.
-
There have been reports regarding recurrences after curative resection in Europe and the United States showing that approximately 50% of the recurrences were detected within 1 year after surgery, that approximately 70% of the recurrences were detected within 2 years after surgery [132, 133]; and that in most patients the recurrences were detected within 5 years after surgery [133].
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The recurrence rate of pT1 (SM) cancer was approximately 1% in both colon cancer and rectal cancer.
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The overall recurrence rate of pT2 (MP) cancer was 6.4%, and it was 5.0% in colon cancer and 8.3% in rectal cancer.
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Two-thirds of the recurrences were detected within 3 years after surgery, and the overall incidence of recurrence more than 5 years after surgery was less than 0.2% among all patients.
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The recurrence rate increased with the Stage.
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78–90% of recurrences were detected within 3 years after surgery, and the overall incidence of recurrence more than 5 years after surgery was less than 1% among all patients.
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A past history of colorectal cancer, regardless of stage, is a risk factor for metachronous colorectal cancer [134].
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The recommended interval between colonoscopy ranged from 1 to 5 years, depending on the report [135].
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The need for surveillance targeting multiple cancers should be determined by distinguishing hereditary colorectal cancer [105]. There is little evidence of a need for periodic minute examinations for cancer in other organs following surgery for sporadic colorectal cancer (CQ-20-2).
sm invasion distance (μm) | Pedunculated | Non-pedunculated | ||
---|---|---|---|---|
Number of lesions |
n (+) (%) | Number of lesions |
n (+) (%) | |
head invasion | 53 | 3 (5.7) | ||
0 < X<500 | 10 | 0 (0) | 65 | 0 (0) |
500 ≤ X < 1000 | 7 | 0 (0) | 58 | 0 (0) |
1000 ≤ X < 1500 | 11 | 1 (9.1) | 52 | 6 (11.5) |
1500 ≤ X < 2000 | 7 | 1 (14.3) | 82 | 10 (12.2) |
2000 ≤ X < 2500 | 10 | 1 (10.0) | 84 | 13 (15.5) |
2500 ≤ X < 3000 | 4 | 0 (0) | 71 | 8 (11.3) |
3000 ≤ X < 3500 | 9 | 2 (22.2) | 72 | 5 (6.9) |
3500 ≤ X
| 30 | 2 (6.7) | 240 | 35 (14.6) |
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Accurate preoperative endoscopic diagnosis is essential in endoscopic resection in regard to lesions with a maximum diameter of 2 cm or greater, and whether resection by EMR, piecemeal EMR, or ESD is indicated is determined after taking the operator’s skill in performing endoscopic resection into consideration. (Recommendation/Evidence level 1B)
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Method for measuring depth of SM invasion (Fig. 11)When it is possible to identify or estimate the location of the muscularis mucosae, depth of SM invasion is measured from the lower border of the muscularis mucosae of the lesion, regardless of the macroscopic type.
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When it is not possible to identify or estimate the location of the muscularis mucosae, the depth of SM invasion is measured from the surface of the lesion. The phrase “possible to identify or to estimate” means that there is no “deformity”, i.e., disarray, dissection, rupture, fragmentation, etc., of the muscularis mucosae as a result of SM invasion. If a deformed muscularis mucosa is used as the base line of the measurement, the depth of SM invasion may be underestimated. Although judging whether there is a “deformity” is not always straightforward, if a desmoplastic reaction is present around the muscularis mucosae, it is assumed to be “deformed.”
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For pedunculated lesions with a tangled muscularis mucosae, depth of SM invasion is measured as the distance between the point of deepest invasion and the reference line, which is defined as the boundary between the tumor head and the stalk (the boundary between the tumor area and the non-tumor area in the mucosa). Invasion by pedunculated lesions that is limited to within the head is defined as “head invasion.”
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Attention to arteries is a key factor in assessing venous invasion. Venous invasion is highly likely when a circular, semicircular, or oblong cancer cell nest with regular margins is located in the vicinity of an artery and distant from the main lesion. If such a cancer cell nest is surrounded by venous wall structures (such as internal elastic membrane or perivascular smooth muscle), it can be concluded to represent venous invasion. However, the venous wall structures are often displaced or obliterated by the cancer cell nest, and it is difficult to recognize in hematoxylin and eosin stained sections.
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The presence of cancer cells and cancer cell nests in the interstitial space suggests lymphatic invasion. A space filled with lymph and lymphocytes is especially likely to be a lymph vessel. When endothelial cells are identified around the space, the space can be concluded to represent a lymph vessel. However, it is often difficult to identify endothelial cells in specimens stained with hematoxylin and eosin, and spaces may be artifacts created during the process of preparing the specimen.
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As stated above, evaluation of vascular invasion, which is an important indicator for determining treatment strategies for SM cancer, is often difficult in hematoxylin and eosin stained specimens. Special staining methods are useful for evaluating vascular invasion, such as elastica van Gieson staining or Victoria blue staining for venous invasion, and D2-40 immunostaining for lymphatic invasion.
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Method for the assessing tumor budding (Fig. 15)
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The lymph node metastasis rate by Grade 2/3 tumors is significantly higher than by Grade 1 tumors. A multi-center study conducted by the Budding Investigation Project Committee (2005–) of the JSCCR in which Grade 1 was defined as “low grade” and Grade 2/3 as “high grade” showed that “high grade” is an independent predictor of lymph node metastasis.
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While ESD is used in cases of “early-stage malignant tumors,” accurate preoperative endoscopic diagnosis and the level of skill of the operator in regard to endoscopic resection should be considered before deciding to proceed. (Recommendation/Evidence level 1B)
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According to randomized controlled trials held overseas and the Cochrane Database of Systematic Reviews, the safety and long-term outcome of laparoscopic surgery in cases of colonic and RS cancers are similar to those in open surgery. As D3 dissection is difficult under laparoscopic conditions, laparoscopic surgery for cStage II–cStage III disease should be implemented when it is considered that the individual surgical team is sufficiently experienced. Laparoscopic surgery is also difficult in patients with transverse colon cancer, in severely obese patients, and in patients with severe adhesions.
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The efficacy and safety of laparoscopic surgery for rectal cancer has not been established. Ideally, appropriately planned clinical trials should be implemented. (Recommendation/Evidence level 1B).
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The efficacy of primary tumor resection in cases with unresectable distant metastasis differs depending on individual factors such as symptoms caused by the primary lesion, the state of distant metastasis, the patient’s general condition, etc.
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The efficacy of resecting peritoneal dissemination has not been proven. Some cases of long-term survival have been reported in which localized dissemination (P1, P2) was resected alongside the primary tumor, suggesting that if the resection is not significantly invasive, then the peritoneal dissemination should be resected at the same time as the primary tumor (recommendation/evidence level 2D).
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The efficacy of resection in patients who have liver and lung metastases at the same time has been shown, and thus resection should be considered for patients with resectable liver and lung metastases.
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The efficacy and safety of adjuvant chemotherapy subsequent to distant metastatic lesion resection in cases of colorectal cancer have not yet been established. Ideally, appropriately planned clinical trials should be implemented. (Evidence level C)
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Resection should be performed for cases in which chemotherapy has successfully made localized metastasis to the liver or lungs operable (recommendation/evidence level 2D).
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Resection should be considered for local recurrence of rectal cancer when R0 resection is considered possible (recommendation/evidence level 2D).
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The efficacy and safety of preoperative chemotherapy for resectable liver metastases has not been established. It should be evaluated in properly designed clinical trials (evidence level D).
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Even in patients 70 years old or older, postoperative adjuvant chemotherapy is recommended if their PS is good, if the function of major organs is adequate, and if there are no complications that may be a risk for performing chemotherapy (recommendation/evidence level 1A).
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The usefulness of postoperative adjuvant chemotherapy for Stage II colorectal cancer has not been proven, and it is recommended not to routinely administer adjuvant chemotherapy to all patients with Stage II colorectal cancer (recommendation/evidence level 1A).
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Although no definitive conclusion regarding the duration of postoperative adjuvant chemotherapy has been reached, the current standard duration of treatment by 5-FU-based adjuvant chemotherapy is 6 months (recommendation/evidence level 1A).
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IRI and UGT1A1 genetic polymorphism
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Comparisons between hepatic arterial infusion therapy using fluoropyrimidine alone and systemic chemotherapy showed no clear difference in survival. The effectiveness of hepatic arterial infusion therapy in comparison with systemic chemotherapy using multi-drug combination has not been established (recommendation/evidence level 1C).
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In the USA and Europe, although preoperative chemoradiotherapy has lowered local recurrence rates in comparison with TME-only, reports suggest that it has not contributed to improved survival rates. In Japan, where surgical methods differ from the USA and Europe, the efficacy of preoperative chemoradiotherapy has not been established in regard to rectal cancers in which the lower margin of the tumor is closer to the anus than the peritoneal reflection (evidence level B).
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It has been suggested that the efficacy of surveillance is its contribution to improving prognosis by allowing the early detection of recurrence, and as such, regular postoperative surveillance is desirable (recommendation/evidence level 1A).
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However, an optimal surveillance protocol incorporating the health economical point of view has not been sufficiently established.