Localized rectal Cancer

DIAGNOSIS, PATHOLOGY AND MOLECULAR BIOLOGY

▪️  From diagnosis, a dedicated multidisciplinary team (MDT) of expert medical oncologists, radiologists, surgeons, radiation oncologists and pathologists should attend regular meetings to discuss patients

Good practice statement.

▪️ A full medical history and physical examination, including digital rectal examination (DRE), complete blood count, liver and renal function tests and measurement of serum CEA, should be carried out

Good practice statement.

▪️ Preoperative colonoscopy to the caecal pole and MRI are recommended to determine tumour level. Tumor height must be defined: low = 0 to <5 from anal verge , mid 5 to <10 cm, upper >10 cm.

Strong recommendation, low grade evidence (5).

▪️ ERUS (if available) is recommended for T staging of localized tumors in cases of cT1 versus cT2.

Conditional recommendation, high grade evidence (6).

▪️  MRI (rectal protocol) is mandatory as part of the staging work-up to stratify for risk-adapted treatment

Strong recommendation, high grade evidence (6)

▪️ MRI reports should include description of tumour infiltration depth, node status, lateral lymph nodes, EMVI status and MRF status 

Strong recommendation, low grade evidence (7).

▪️  The recommended high-risk criteria are cT4a or cT4b, involved or threatened mesorectal fascia (MRF+), cN2 (4 uspicious nodes), EMVI + and lateral lymph node enlargement of 7 mm . 

Strong recommendation, low grade evidence (8).

▪️ Contrast-enhanced CT of the chest and abdomen is recommended for distant staging.

Strong recommendation, low grade evidence (9).

▪️  Fertility risk discussion is recommended in appropriate patients.

Good practice statememt

MANAGEMENT OF LOCALISED DISEASE

RT and CRT

For lower or middle third tumours when surgery is intended:

▪️ Preoperative RT followed by LE cannot generally be recommended in patients with cT2 N0 tumours <4 cm  but may be considered for selected patients (e.g. elderly or frail patient at high surgical risk).

Conditional recommendation, low grade evidence (10).

▪️  Neoadjuvant SCRT or CRT (not TNT) is recommended for patients with cT2 N+, cT3 N0 or cT3 N1 tumours

Strong recommendation, high grade evidence (11,12).

For lower or middle third tumours when watch-and-wait approach is intended:

▪️  SCRT or CRT is recommended for patients with cT1-cT2 N0 tumours

Strong recommendation, high grade evidence (11,12).

Total neoadjuvant therapy (TNT).

▪️  RT should be offered as long-course CRT (50-50.4 Gy in 25-28 fractions with concomitant capecitabine or infusional 5-FU) or SCRT (25 Gy in five fractions)

Strong recommendation, high grade evidence (13-15).

▪️  Consolidation or induction chemotherapy (CAPOX or FOLFOX) should be administered for 4-6 cycles (i.e. 3-4.5 months)

Strong recommendation, high grade evidence (16).

▪️  If FOLFIRINOX regimen is used, it may be administered in line with the protocol of the PRODIGE 23 trial (indications and doses), see Annex.

Conditional recommendation, high grade evidence (17).

For upper third tumours:

▪️  TNT should be offered to patients with cT4 or involved or threatened MRF

Strong recommendation, high grade evidence (18).

▪️  CRT or SCRT should be considered if TNT is not feasible

Strong recommendation, high grade evidence (19).

For lower or middle third tumours when surgery is intended:

▪️  TNT should be offered to patients with high-risk criteria

Strong recommendation, high grade evidence (13).

For lower or middle third tumours when watch-and-wait approach is intended:

▪️  TNT is recommended for patients with high-risk criteria and patients with cT2 N+ or cT3 any N

Strong recommendation, high grade evidence (20).

▪️  Upfront CRT followed by consolidation chemotherapy is recommended to increase the likelihood of cCR.

Strong recommendation, high grade evidence (20).

Neoadjuvant Chemtherapy

▪️ When considering neoadjuvant chemotherapy, the inclusion criteria of the PROSPECT study should be used (T2 N+, T3 any N, distance to the CRM ≥3 mm, continence-preserving surgery possible)

Strong recommendation, high grade evidence (21-23).

▪️  Neoadjuvant chemotherapy should comprise 3 months of CAPOX or FOLFOX

Strong recommendation, high grade evidence (21-23).

For upper third tumours:

▪️  Neoadjuvant chemotherapy is recommended for patients with cT2 N+ or cT3 any N disease

Strong recommendation, high grade evidence (21-23).

▪️ Neoadjuvant chemotherapy is recommended for patients with cT4 any N disease.

Strong recommendation, very low grade evidence (24).

For lower or middle third tumours when surgery is intended:

▪️ Neoadjuvant chemotherapy is recommended for patients with cT2 N+, cT3 N0 or cT3 N1 disease

Strong recommendation, high grade evidence (21-23).

▪️   Salvage RT is recommended in case of intolerance to, or progression on, neoadjuvant chemotherapy

Strong recommendation, high grade evidence (25).

Restaging before surgery or watch-and-wait approach

▪️  Restaging should comprise MRI, endoscopy and DRE

Strong recommendation, high grade evidence (26,27). 

▪️  In case of a cCR, biopsies are not recommended to determine a watch-and-wait approach, as their value in this setting is unclear.

Strong recommendation, low grade evidence (28,29).

Surgery

▪️  PME and TME are the recommended surgical procedures for rectal cancer

Strong recommendation, low grade evidence (30).

▪️ Open surgery and minimally invasive approaches are both recommended as they lead to similar oncological results

Strong recommendation, high grade evidence (31).

▪️  A distance of >1 mm from tumour to CRM and other organs is recommended.  In case of MRF + or T4b, beyond TME surgery is recommended.

Strong recommendation, low grade evidence (32).

▪️  The distal mesorectal margin should be >5 cm.

Strong recommendation, low grade evidence (32).

▪️  A distal resection margin of  >1 cm is recommended.

Strong recommendation, low grade evidence (33,34).

▪️  Lateral lymph nodes with a short axis of >7 mm should be resected after neoadjuvant treatment

Strong recommendation, very low grade evidence (35).

For upper third tumours:

▪️   PME and TME are both equally recommended.

Strong recommendation, low grade evidence (36).

▪️  LE is recommended as an alternative to PME or TME for low-risk tumours (pT1 without unfavourable pathological features).

Strong recommendation, low grade evidence (37).

For lower or middle third tumours when surgery is intended:

▪️  TME is the recommended surgical procedure.

Strong recommendation, low grade evidence (38).

▪️  LE should be considered as an alternative to TME for low-risk tumours (pT1 without unfavourable pathological features).

Strong recommendation, low grade evidence (37).

For lower or middle third tumours when watch-and-wait approach is intended:

▪️  Surgery, with the resection method depending on clinical assessment, is recommended for patients who do not achieve a cCR following CRT or TNT.

Strong recommendation, high grade evidence (39).

▪️ In case of local (endorectal) regrowth after a watch-and-wait procedure, salvage resection should be offered to all patients.

Strong recommendation, low grade evidence (37).

Watch and wait approach

▪️  For lower or middle third tumours, a watch-and-wait strategy is recommended in patients with cCR when organ preservation is intended.

Strong recommendation, high grade evidence (40).

▪️ Discussion with patients about the importance of adherence to strict follow-up investigations is mandatory.

Good Practice Statement

▪️  Follow-up examinations should comprise MRI, endoscopy and DRE every 3 months for the first 2 years and every 6 months thereafter. CT scans of the chest and abdomen should be carried out every 6 months for the first 2 years and annually thereafter

Strong recommendation, high grade evidence (41).

Adjuvant therapy

For upper third tumours:

▪️  Adjuvant Chemotherapy with a fluoropyrimidine and (potentially) oxaliplatin should be offered (according to clinical risk assessment) following PME or TME alone

Strong recommendation, high grade evidence (42,43).

▪️ In patients who did not receive preoperative RT, adjuvant CRT should be offered in case of CRM positivity, pT4b, pN2 with extracapsular spread close to the MRF or poor-quality TME

Strong recommendation, low grade evidence (44).

For lower or middle third tumours after surgery:

▪️  Adjuvant therapy with a fluoropyrimidine and (potentially) oxaliplatin should be offered (according to clinical risk assessment) following TME alone

Strong recommendation, high grade evidence (42,43).

▪️  Adjuvant therapy with a fluoropyrimidine and (potentially) oxaliplatin is recommended after neoadjuvant CRT or SCRT.

Strong recommendation, low grade evidence (45).

▪️ In patients who did not receive preoperative RT, adjuvant CRT should be offered in case of CRM positivity, pT4b, pN2 with extracapsular spread close to the MRF or poor-quality TME.

Strong recommendation, low grade evidence (44).

For lower or middle third tumours for watch-and-wait approach:

▪️  An adjuvant fluoropyrimidine oxaliplatin combination can be offered on a case-by-case basis after RT or fluoropyrimidine-based CRT in patients achieving cCR with initial cN+ disease

 Conditional  recommendation, high grade evidence (42,43).

▪️  Post-neoadjuvant systemic treatment following TNT (irrespective of surgical or nonsurgical local approach) cannot be generally recommended due to toxicity considerations. This approach should be discussed individually within an MDT

Conditional recommendation, high grade evidence (42,43).

 CLINICAL MONITORING, LONG-TERM IMPLICATIONS, AND SURVIVORSHIP

▪️  Clinical examination, pelvic MRI and/or CT can be recommended for detection of locoregional recurrence.

Good practice statement.

▪️  Proactive surveillance for local recurrence can be considered in patients at high risk of recurrence (e.g. involved CRM)

Good practice statement.

▪️ Clinical assessment should be carried out every 3 months for 2 years

Good practice statement.

▪️ Serum CEA measurements can be recommended every 3-4 months for the first 3 years

Good practice statement.

▪️ Annual (minimum) CT scan of the chest, abdomen and pelvis can be recommended after the first 2 years for detection of distant metastases.

Good practice statement.

▪️  A completion colonoscopy is recommended within the first year (preferably after 6 months) if not carried out at the time of diagnostic work-up (e.g. if an obstruction was present)

Good practice statement.

▪️  Medical history and colonoscopy with resection of colonic polyps can be recommended every 5 years up to the age of 75 years

Good practice statement.

▪️  Long-term side-effects of treatment should be monitored

Good practice statement.