Neoadjuvant vs Adjuvant Therapy and Surgical
Options
Paul A. Lucha Jr., DO, FACOS
Capt (ret), MC, USN
WG Hefner VA Medical Center, Salisbury NC

Introduction
 Preoperative Evaluation
 Imaging in rectal cancer
– TRUS
– MRI
– CT
– PET scanning

Introduction
 Surgical Approaches
– transanal excision
– Sphinter sparing
– TME (circumferential margin)
– nerve sparing

Introduction
 Surgical Approaches
– Laparoscopic Surgery
– Endoscopic Surgery

WALL Stent
 Transanal endoscopic microsurgery
 Adjuvant therapy
– neoadjuvant vs postoperative
 Quality of life measures

Preoperative Evaluation
 relevant anatomy

Preoperative Evaluation
 relevant anatomy

Preoperative Evaluation
 clinical evaluation (DRE)
– 44-83% Accuracy for depth of tumor penetration
– Fixed
– palpable nodes (60% accurate at best)
– accuracy related to examiners experience
– smaller tumors often staged inaccurately
 Rigid Sigmoidoscopy
– level of tumor above the dentate line
– position of tumor

Preoperative Evaluation
 TRUS
– “gold standard” for preoperative assessment
– depth of penetration through bowel wall (81-96% accurate)
– perirectal lymph node involvement (60-83% accurate)
– operator dependent

 TRUS
– T2NxMx
 TRUS
– T1NxMx

Preoperative Evaluation
 Trus
– T2N0M0
– Pathologic Specimen

Preoperative Evaluation
 TRUS
– T3NxMx
– Penetration into perirectal fat

Preoperative Evaluation
 CT
– better assessment of local regional involvement
– can detect metastatic disease outside the confines of the rectum
– unable to detect layers of bowel wall
– poor at assessing lymph node status

Preoperative Evaluation
 CT
– initial reports quoted 77-100% accuracy in staging
 mostly advanced stage tumors
– poor at assessing node status (50% accurate at best)
– Up to 25% may have metastatic disease at the time of presentation
 CT more useful to assess liver, adrenal, lungs
 90% accurate in assessing liver metastasis

Preoperative Evaluation


CT
T3N0M0

Preoperative Evaluation


CT
Metastasis

Preoperative Evaluation


CT
Hamartoma

Preoperative Evaluation
 MRI
 Similar in accuracy to TRUS
– If endorectal coil used
 Better than CT for local pelvic spread
 Superior to CT for liver metastasis

Preoperative Evaluation
 MRI (endorectal coil)
– can distinguish 3 rectal wall layers
 Inner layer (mucosa and submucosa)
– Intermediate signal on T1
– High signal on T2
 Middle layer (Muscularis propria)
– low signal on T1 and T2
 Outter layer (subserosa, serosa, perirectal fat)
– High signal on T1 and T2

Preoperative Evaluation



MRI (endorectal coil)
– T stage sensitivities between 70-92%
– Lymph node status about
40% in some series
Better for recurrent rectal tumors
T3N0M0

Preoperative Evaluation
 PET
– F-18-labeled -2-deoxyglucose
(FDG)
– Tumors with increased glucose utilization
– Inflammation may cause false positivity
– little role in primary diagnosis and evaluation
 understages small lesions
(<1cm)
 necrotic neoplasms
 peritumoral inflammatory granulomas

Surgical Approaches
 Local treatment to avoid colostomy or major resection
 Key to success is patient selection (3-5% of all rectal tumors)
– small exophytic tumor
 <3 cm diameter
 < 25% of rectal circumference
 uT1NxMx by TRUS

Surgical Approaches
– mobile on exam
– well differentiated pathology
 not mucinous
 not colloid
 no lymphovascular invasion

Surgical Approaches
 Risk of lymph node metastasis
– by T stage
 pT1 is 12%
 pT2 is 22%
– by tumor grade
 0% for grade 1 histology
 22% for grade 2 histology
 50% for grade 3 histology
– by lymphovascular invasion
 17% non invasive
 31% invasive

Surgical Approaches
 Transanal Excision
– uT1
– 1 cm margins
– defect left open or closed
– full thickness excision
 Transanal Endoscopic Microsurgery
– operating resectoscope
– ? Improved exposure
– higher rectal lesions accessible

Surgical Approaches
 TAE or TEM
– adjuvant therapy if final pathology
 positive margins
 pT2 or pT3 and patient refused resection

Surgical Approaches
 Endoscopic Surgery
– Wall Stent
 palliative treatment for obstructing cancer
 preoperative treatment of obstructing cancer
– avoidance of stoma
– allows bowel prep
– preoperative neoadjuvant therapy to downstage tumor (or improve resectability)

Surgical Approaches
 Nerve Sparring
– most are injured during blunt dissection
– wide lateral dissection damages the remainder
 Total Mesorectal Excision (TME)
– Local recurrence rates of 4-8% without adjuvant therapy
– initial studies included patients who had had XRT preoperatively and chemotherapy postoperatively
– Dutch Colorectal Cancer Group TME trial
– Randomized Dutch trial examined the role of adjuvant therapy in patients undergoing TME

Surgical Approaches
 TME
– Heald 1992 (Basingstoke Experience)
 2.6% local recurrence rate at 5 years
– Enker 1995 (Memorial Experience)
 7.3 % local recurrence rate at 5 years
– anastomotic leak rate higher (17%)
– proximal diversion recommended
– lower rates of sexual and urinary tract dysfunction

Surgical Approaches
 Colonic J pouch- randomized studies show
– Decreased mean stool frequency (<2/24 hours)
– Improved continence
 less rectal urgency
– increased maximum volume and compliance by manometry
 benefits persist for up to two years
– Fewer anastomotic leaks
 ? Better blood supply
– Diverting stoma recommended

Surgical Approaches
 Laparoscopic surgery
– Adequacy of resection
 length of specimen andlength of margin
 number of lymph nodes harvested
– Short term
 length of operating time and hospital stay
 postoperative pain and ileus
 cytokine response
– Long term
 return to “work”
 cancer survival

Surgical Approaches
 Laparoscopic surgery
– port site/ extraction site recurrences
– long term cancer free survival
– Randomize prospective trial results
 COST Trial
 Longer operative times
 Shorter hospital stay
– Offsets operative costs

Surgical Approaches
 Endocavitary Irradiation (Papillon tx)
– no pathologic staging
– criteria the same as for TEM or TAE
– often used in those with high surgical risk
 ? High rectal tumors not amenable to TAE
 Electrofulgeration
– similar limitations and requirements to endocavitary irradiation
– morbidity rates higher (21%)
 postoperative bleeding
 postoperative stricture

Adjuvant Therapy
 NCI Concensus Conference 1990
– Combined modality therapy for T3 and/or N1-2 disease
– XRT and 5FU
– decreases local recurrence rates to about 10%
– Increased 5-year survival by 10-15%
– significant acute toxicity
 25-50%

Adjuvant Therapy
 Neoadjuvant therapy Advantages
– decreased tumor seeding?
– Less toxicity
– increased radiosensitivity
 increased oxygen
– enhanced sphincter preservation

Adjuvant Therapy
 Neoadjuvant therapy disadvantages
– ? Overtreatment
– ? Downstaging tumor (retrospective data)
– ? Sphincter dysfunction
– ? Increased risk for incontinence

Adjuvant Therapy
 Neoadjuvant therapy (45-50Gy in 4-5 weeks)
– complete response rate 10%
– local recurrence rate 3-10%
– acute toxicity rate 15-25%
– Swedish Rectal Cancer Trial (25Gy in one week)
 improved survival
 short course therapy
– No other trials show improved survival

Meta analysis, subset analysis, etc

Adjuvant Therapy
 Preoperative downstaging (sphincter preservation)
– 4-5 week course of 50 Gy
– 4-6 weeks wait until surgical treatment
– interim analysis of NSABP R-03
 27% increase in sphincter preservation
 Improved survival
– short course therapy?

Quality of Life measures
 Traditional measures of cancer treatment
– Disease free survival
– Overall survival
– Tumor response rates
 Quality of life difficult to measure
– subjective
– validated questionaires
– must be cancer/ surgery specific

Quality of Life measures
 Incontinence
 Impotence (retrograde ejaculation)
 Bladder dysfunction
 Rectal urgency
 Pain
 Frequency of Bowel movements
 Psychosocial dysfunction
– stoma related
– cancer related

Quality of Life measures
 Chemotherapy or Radiation treatment related
– nausea
– diarrhea
– vomiting
– weakness
– Xerostomia
– Insomnia
– Weight Loss
 Few Studies in the English Literature address this topic

Controversies
 Distal Margin of resection
– 5 cm margin
 studies show that intramural spread of tumor less that 1 cm
 2 cm margin acceptable
 No difference in long term survival 2 cm vs 5 cm
 Some will accept 1 cm margin for exophytic lesions
– measurement of margins
 Weese (1986)
– 5 cm margin fresh pinned specimen
– 2.4 cm margin in the fixed state

Controversies
 Distal rectal washout
– tumorcidal agent
– rectum must be occluded below tumor
 Neoadjuvant therapy vs postoperative therapy
 Preoperative staging
– MRI (endorectal coil)
– TRUS

Controversies
 High vs Low ligation of IMA
– no good evidence that ligation proximal to the left colic artery improves survival
 TME
– adjuvant therapy?
 Colonic J pouch
 Laparoscopic Resection


– Distal to the peritoneal reflection (5-8 cm)

– Oncologic outcomes of surgical treatment were most important
– Functional outcomes rarely considered
 QOL research and functional assessment have become more important

– Adjunctive treatments changed
 Radiation therapy
– Preoperative or Postoperative
– Compromised rectal function with postoperative XRT
• Reduced compliance of reservoir
– Sphincter dysfunction after XRT (pre and post operative)
 Chemotherapy


– Local Options
 Transanal Endoscopic Microsurgery
 Transanal Excision
 Endocavitary Irradiation (Papillon tx)
 Fulgeration


– Resection
 Abdominal Perineal Resection
 Total Mesorectal Excision
– Straight end to end coloanal anastomosis
– Coloplasty
– Side to end coloanal anastomosis (Baker)
– Colonic J pouch
 Pullthrough (Harry E. Bacon MD)

Surgical Approaches- Local
 Transanal Excision
– uT1
– 1 cm margins
– defect left open or closed
– full thickness excision
 Transanal Endoscopic Microsurgery
– operating resectoscope
– ? Improved exposure
– higher rectal lesions accessible

Surgical Approaches- Local
 Endocavitary Irradiation (Papillon tx)
– no pathologic staging
– criteria the same as for TEM or TAE
– often used in those with high surgical risk
 ? High rectal tumors not amenable to TAE
 Electrofulgeration
– similar limitations and requirements to endocavitary irradiation
– morbidity rates higher (21%)
 postoperative bleeding
 postoperative stricture

Surgical Approaches- Local

– Since these are local procedures, functional outcome is primarily related to stage of disease
– When applied with curative intent, minimal changes are noted in QOL or functional outcomes measured

Surgical Approaches- Resection

– Traditionally used for low rectal cancer
– Permanent Colostomy
 Efforts to later recreate a sphincter popularized in Europe (Spain)
– Sphincter reconstruction not attempted in
US
– Functional Outcome self evident

Surgical Approaches-
Resection
 Total Mesorectal Excision (TME)
– Local recurrence rates of 4-8% without adjuvant therapy
– initial studies included patients who had had XRT preoperatively and chemotherapy postoperatively
– Dutch Colorectal Cancer Group TME trial
– Randomized Dutch trial examined the role of adjuvant therapy in patients undergoing TME

Surgical Approaches-
Resection
 Straight coloanal anastomosis
– Most have 1-2 BM/ day
– About 33% will have
>3 BM/ day
– Rectal Urgency with urgency related incontinence can occur

Surgical Approaches- Resection
 Coloplasty
– Described in 1999 by
Z’graggen and Mauer
– May not require as much mobilization
– Ideally suited for narrow pelvis
– Performed 4 cm above cut end of proximal segment
– 7 cm longitudinal incision in taenia on antimesenteric side

Coloplasty

Surgical Approaches- Resection
 Side to end coloanal anastomosis
– Described in 1950 by
JW Baker
– Revived and more popular in Europe
– Functionally similar to J pouch at 6 months


Surgical Approaches-
Resection
Colonic J pouch- randomized studies show
– Decreased mean stool frequency
(<2/24 hours)
– Improved continence
 less rectal urgency
– increased maximum volume and compliance by manometry
 benefits persist for up to two years
– Fewer anastomotic leaks
 ? Better blood supply
– Diverting stoma recommended

Surgical Approaches- Resection

– 6-7 cm long pouch
– 15 cm pouch with poor function and evacuation
 Similar to straight coloanal anastomosis

Surgical Approaches- Resection
 Pullthrough
– Popularized in US by Harry E. Bacon
– Intersphincteric dissection
– No anastomosis therefore no leak
– Vascular supply to segment
 Compromise with ischemia and necrosis
– Segment of left colon is brought through the anus
 Anoplasty is accomplished at POD#7
– Poor functional outcome


Poor evacuation
Daily enema to evacuate



Colonic J pouch with fewer BM/ day
– Average 3
– Better compliance and evacuation on scintography and manometry
– Less urgency
Coloplasty
– Similar outcomes to J-pouch (manometry/ scintography)
– Fewer randomized trials
– Higher leak rates than J-pouch
– QOL scores (SF 36) similar to J- pouch


– Similar leak rate to J-pouch
– Poorer function at 3 months
– Similar evacuation function at 6 months

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