Management of Rectal cancer

Management of Rectal cancer

Transrectal ultrasound EUS

use for clinical staging.80-95% accurate in tumor staging70-75% accurate in mesorectal lymph node stagingVery good at demonstrating layers of rectal wallUse is limited to lesion < 14 cm from anus, not applicable for upper rectum, for stenosing tumorVery useful in determining extension of disease into anal canal (clinical important for planning sphincter preserving surgery)

Figure. Endorectal ultrasound of a T3 tumor of the rectum, extension through the muscularis propria, and into perirectal fat.

CT scanPart of routine workup of patientsUseful in identifying enlarged pelvic lymph-nodes and metastasis outside the pelvis than the extent or stage of primary tumorLimited utility in small primary cancerSensitivity 50-80%Specificity 30-80%Ability to detect pelvic and para-aortic lymph nodes is higher than peri-rectal lymph nodes.

Figure: Mucinous adenocarcinoma of the rectum. CT scan shows a large heterogeneous mass (M) with areas of cystic components. Note marked luminal narrowing of the rectum (arrow).Figure: Rectal cancer with uterine invasion. CT scan shows a large heterogeneous rectal mass (M) with compression and direct invasion into the posterior wall of the uterus (U).

Magnetic Resonance Imaging (MRI)Greater accuracy in defining extent of rectal cancer extension and also location & stage of tumor

Also helpful in lateral extension of disease, critical in predicting circumferential margin for surgical excision.

Different approaches (body coils, endorectal MRI)

Stage Grouping

Stage and PrognosisStage5-year Survival (%)

0,1Tis,T1;No;Mo> 90IT2;No;Mo80-85IIT3-4;No;Mo70-75IIIT2;N1-3;Mo60-70IIIT3;N1-3;Mo50-65IIIT4;N1-2;Mo25-45IVM1M)Asymptomatic ptsPolypoidal lesionsDiploidPoor prognostic factorsObstructionPerforationUlcerative lesionAdjacent structures involvementPositive marginsLVSIPNI Signet cell carcinomaHigh CEATethered and fixed cancer

12

PRINCIPLES OF PATHOLOGIC REVIEWThe following parameters should be reported:

Grade of the cancer

Depth of penetration (T), the T stage, is based on viable tumor.

Acellular mucin pools are not considered to be residual tumor in those cases treated with neoadjuvant therapy.

Number of lymph nodes evaluated and number positive (N).

Acellular mucin pools are not considered to be residual tumor in those cases treated with neoadjuvant therapy

Status of proximal, distal, and circumferential (radial) margins.A positive circumferential resection margin (CRM) has been defined as 1 mm

Neoadjuvant treatment effectLymphovascular invasionPerineural invasionExtranodal tumor deposits

Surgery Surgery remains the mainstay of curative treatment for carcinoma of the rectum

Surgical management depends on the stageand location of a tumor within the rectum.

GOALThe general principles of a surgical approach remain the removal of all gross and microscopic disease with negative proximal, distal, and circumferential margins

reserve intestinal continuity and the sphincter mechanism whenever possible while still maximizing tumor control

Early cancers can be managed with limited surgery

majority of tumors tend to present as more advanced disease

require either a low anterior resection (LAR) or abdominoperineal resection (APR).

Local Excision

Polypectomy

Transanal excision

Transanal endoscopic microsurgery (TEM)

patients need to be carefully selected for these procedures

Transanal Excisionselected T1, N0 early-stage cancers.

Small (3 mm) deep and mucosal margins are required, and tumor fragmentation should be avoided.

The excised specimen should be oriented and pinned before fixation

brought to the pathologist by the surgeon to facilitate an oriented histopathologic evaluation of the specimen.

Advantages of a local procedure include minimal morbidity (eg, a sphincter-sparing procedure) and mortality

rapid postoperative recovery.

If pathologic examination reveals adverse features

positive margins, LVI, poor differentiation, or invasion into the lower third of the submucosa

a more radical resection is recommended

Limitations of a transanal excision include the absence of pathologic staging of nodal involvement

lymph node micrometastases are both common in early rectal lesions and unlikely to be identified by endorectal ultrasonogram or MRI

A recent retrospective study of 282 patients undergoing either transanal excision or radical resection for T1 rectal cancer from 1985 to 2004

showed respective local recurrence rates of 13.2% and 2.7% for these 2 groups

Transabdominal ResectionAbdominoperineal Resection

APR has been considered the gold standard for surgical resection of distal rectal cancer located within 6 cm of the anal verge.

This procedure requires a tranabdominal as well as a transperineal approach with removal of the entire rectum and sphincter complex.

A permanent end colostomy is created and the perineal wound either closed primarily or left to granulate in after closure of the musculature

APR is associated with a slightly higher morbidity and mortality than LAR

a worse quality of life related to changes in body image and depression due to the presence of a colostomy

There is also a higher risk of positive margins with APR as the mesorectum is very thin in the distal segment of the rectum

lateral margins are restricted by the close presence of the prostate in the male and vagina in females

The bony confines of the lower pelvis also restrict surgical access especially in males.

Low Anterior ResectionThe availability of circular stapling devices has expanded the role of sphincter preservation surgical options in rectal cancers

LARs are now being performed not just for cancers of the upper third of the rectum but also for middle and lower third cancers

Preserving adequate anorectal function becomes a bigger problem the more distal the level of anorectal anastomosis

Patients should have good anal sphincter continence prior to considering sphincter-preserving options

A 2-cm distal margin of preserved normal rectum is considered optimal for preservation of good bowel function.

In carefully selected patients a functional coloanal anastomosis can be achieved with significantly reduced margins for more distal cancers especially after neoadjuvant therapy.

Advances in stapling instruments have been very important as aids in reconstruction.

Narrow, low-profile staplers allow the surgeon to place a staple line across the rectum at the level of the anorectal ring or below.

This, combined with the circular stapler, allows the surgeon to construct a quick and reliable double-stapled anastomosis even at the level of the anal canal.

Total Mesorectal ResectionIn the rectum the mesorectum is the structure that contains the blood supply and lymphatics for the upper, middle, and lower rectum.

Most involved lymph nodes for rectal cancers are found within the mesorectum

T1 lesions associated with positive lymph nodes in 5-7%T2 -20% T3 -65%T4-78%

Bill Heald from Basingstoke, England, 1982, first began to write about his technique of TME

He recognized that most local recurrences seen after rectal cancer resection were a result of inadequate resections performed using imprecise, blunt dissection.

He recognized that by using meticulous, sharp dissection, under direct vision

staying between the visceral and parietal pelvic fascia down to the level of the levators, or upper aspect of the anal canal

the rectum and its mesentery could be removed as an intact unit

A TME involves an en bloc removal of the mesorectum, including associated vascular and lymphatic structures, fatty tissue, and mesorectal fascia as a tumor package

through sharp dissection and is designed to spare the autonomic nerves

After a TME the specimen is typically shiny and bilobed in contrast to the irregular and rough surface after a blunt dissection where much of the mesorectal fat is left behind.

TME attempts not only to clear involved lymph nodes but also to adequately manage the radial margins of the rectal tumor.

Distal mucosal margins of 1 cm or greater are adequate for local control

however, the margin on the mesorectum should extend beyond the distal mucosal margin in order to ensure a successful surgical outcome.

positive CRM as tumor within 1 mm from the transected margin

786 patients from August 1993 to July 2002. Of these, 622 patients (395 men and 227 women; median age, 67 years) underwent anterior resection.

mid and distal rectal cancer were treated with TME

The local recurrence rate was 9.7% and the cancer-specific survival was 74.5%.

37

Laparoscopic ResectionThe phase III COLOR II trial, powered for noninferiority

randomized patients with localized rectal cancer to laparoscopic or open surgery.

patients in the laparoscopic arm lost less blood, had shorter hospital stays, and had a quicker return of bowel function,

had longer operation times.

No differences were seen in completeness of resection, percentage of patients with positive CRM, morbidity, or mortality between the arms

Role of Combined Modality TherapyOlder studies demonstrate local failure rates of up to 50% in patients with T3-4 or N+ disease

Local failure is related not just to the stage of the disease

but also the location of the tumor in the rectum

experience and ability of the surgeon.

the relevance of these older local recurrence data has been brought into question with the advent of the use of TME39

initial studies reported local-regional failure rates of less than 5% after TME without the use of any adjuvant therapy

there was concern that these excellent results could not be replicated in larger population-based studies

As most of surgeries done even now are not proper TME

41

Adjuvant TherapyThe problem of unacceptably high local recurrence after surgery has led to many studies exploring the potential benefit of postoperative adjuvant therapy

Advantages of postoperative radiation

ability to selectively treat patients at high risk of local failure on the basis of pathologic stage

Disadvantages

potentially hypoxic postsurgical bed, making radiation less effective

higher complications due to increased small bowel in the radiation field

a larger treatment volume, especially if the patient undergoes an APR and the perineal scar needs to be covered

There have been several large trials of postoperative radiation with or without chemotherapy.

In general, surgery alone has resulted in a 25% local failure rate and 40% to 50% overall survival for T3 or T4 or node-positive patients

while radiation with the addition of chemotherapy has yielded a lower local failure rate of 10% to 15% and higher overall survival rate of 50% to 60%.

Earlier studiesNSABP R-01study (randomized 555 patients into three arms after surgery: (a) observation, (b) postoperative chemotherapy of eight cycles of MOF (5FU, CCNU [semustine], and vincristine), and (c) postoperative radiation treatment alone of 46 to 47 Gy Postoperative chemotherapy improved disease-free survival but not overall survival.

Postoperative radiation treatment trended toward improved local control but not overall survival

NSABP R-02 studyenrolled 694 stage B and C patients

asked two questions in its study design

(a) Does the addition of radiation to chemotherapy improve outcome?

(b) Is MOF superior to 5-FU/LV

The radiation dose was 50.4 Gy.

At 5 years, the LRF was 13% for the chemotherapy VS 8% with the addition of radiation and chemotherapy.

5-FU/LV showed better relapse-free survival and disease-free survival but not overall survival as compared to MOF

Conclusion of 2 NSABP trials- while postoperative radiation treatment did not appear to improve overall survival

there was an improvement in local control.

Gastrointestinal Tumor Study Group (GITSG)

North Central Cancer Treatment Group (NCCTG) studies

show an improvement in survival

GITSG studyfour-arm trial of 227 patients with stage B2 and C rectal cancer who were randomized to either

(a) surgery alone

(b) postoperative chemotherapy of bolus 5-FU (500 mg/m2 in weeks 1 and 5 and methyl-CCNU (semustine given day 1)

(c) postoperative radiation treatment of 40 to 48 Gy split course

(d) postoperative chemotherapy and radiation therapy of 40 to 44 Gy plus bolus 5-FU

In a 9-year update

Post op CRT improved the overall survival to 54% versus 27% with observation after surgery.

There was a prolonged time to recurrence and a decreased recurrence rate of 33% versus 55%.

Local failure rate was decreased to 10% versus 25% with surgery alone

Mayo-NCCTGCompared postoperative radiation therapy against postoperative radiation therapy and chemotherapy

The 5-year local regional failure was higher in the radiation only arm of 25% versus 15%

5-year overall survival rate was 40% versus 55%.

reduced local recurrence by 46% and distant metastases by 37%.

Cancer deaths were reduced by 36%, and overall deaths were reduced by 29%.

Ideal chemotherapeutic agent?

Intergroup 0114 study(a) bolus 5-FU alone(b) 5-FU and leucovorin(c) 5FU plus levamisole(d) 5-FU and leucovorin plus levamisole.

The radiation treatment dose was 45 Gy with a 5.4- to 9-Gy boost to a total of 50.4 to 54 Gy.

With a median follow-up of 7.4 years

there was no difference in overall survival or disease-free survival among the four groups.

The three-drug regimen had a greater toxicity.

Levamisole and leucovorin did not appear to add any benefit to the 5-FU.

NEO ADJUVANT THERAPYDue to potential disadvantages of post op RT

potentially hypoxic postsurgical bed, making radiation less effective

higher complications due to increased small bowel in the radiation field

a larger treatment volume, especially if the patient undergoes an APR and the perineal scar needs to be covered

Although both pre- and postoperative adjuvant therapy can be effective

there has been a significant recent trend toward greater use of neoadjuvant treatment

Tumor down staging, improved resectability, and potential for expanded sphincter preservation options in the distal rectum also encourages

Studies from Europe have demonstrated that appropriate neoadjuvant preoperative radiation results in improvement of both local control and survival

these results have had a significant impact on the current management of this disease

NEOADJUVANT RADIATION

Main flaw of study is that the surgery alone arm did not utilize TME

which may have resulted in an unacceptably high local failure rate of 27%

Late effects suggested more bowel movement frequency, incontinence, urgency, and soiling in the preoperative radiation treatment arm, although overall quality of life was rated good

the dose of 5 Gy times five fractions may induce significant acute and late toxicity

the short interval between radiation and surgery may not have allowed sufficient time for tumor regression (downstaging) for improved sphincter preservation.

TME alone is required?A Dutch (CKVO 95-04) multicenter, phase III study

1,861 patients was undertaken to evaluate the role of short course preoperative radiation with TME.

TME alone versus 25 Gy in five fractions followed by TME surgery

No fixed tumors were included in the study, and half of the patients had T1 or T2 disease

RESULTSThe OS was same (82% at 2 years).

However the local recurrence at 2 years was 8.2% in the TME-only arm as compared to 2.4% in the preoperative arm

This study highlighted the value of radiation treatment, even with TME

The sphincter preservation rate was the same in both arms

and there was no clear evidence of any downstaging effect

The perineal complication rate was slightly higher in the preoperative radiation arm of 26% versus 18%.

A more recent update indicates a higher incidence of sexual dysfunction and slower recovery of bowel function

More fecal incontinence and generally poorer quality of life with short-course preoperative radiation

META ANALYSISTwo meta-analyses of approximately 6,000 patients each were done to explore the benefit of preoperative radiation treatment

They noted a significant reduction in the risk of local recurrence and death from rectal cancer with preoperative radiotherapy

Neoadjuvant ChemoradiationThe improvement in outcomes with combined chemoradiation and postoperative adjuvant therapy has led to similar recent approaches in the neoadjuvant therapy of this disease

French study FFCD 9203Patients with resectable T3 and T4 tumors were randomized to 45 Gy of radiation alone

versus radiation with concurrent bolus 5-FU (350 mg/m2) plus leucovorin on days 1 to 5 during weeks 1 to 5

After surgery, four cycles of adjuvant chemotherapy were given.

With a median follow-up of 69 months, there was an equivalent rate (51%) of sphincter-sparing surgery.

Combined treatment led to improved PCR rate of 11.4% versus 3.6%

improved 5-year local failure rate of 8% versus 16.5%.

There was, however, no difference in overall survival

SHORT COURSE VS LONG COURSE RTPolish rectal cancer group

(5 Gy for five fractions) VS 50.4 Gy using 1.8 to 2 Gy fractions with concomitant bolus 5-FU and leucovorin given during weeks 1 and 5

higher PCR was seen with chemoradiation (16% vs. 1%), fewer positive radial margins (4% vs. 13%), and considerably reduced size of the tumor by approximately 1.9 cm

no difference in the rate of sphincter preservation, local control or survival was seen.

Preoperative Versus PostoperativeThe definitive phase III study in favor of preoperative radiation therapy was the CAO/ARO/AIO-94 study performed by the German Rectal Cancer group

Schema of the German rectal cancer trial

RESULTSThe 5-year results revealed a pelvic recurrence ratio of 6% versus 13% (p = 0.02) in favor of the preoperative arm.

No differences in DFS ,OS, or distant failures

There was significant tumor downstaging with an 8%PCR.

Nodal positivity was 25% VS 40%

sphincter-preserving low anterior resection 39% versus 19% had a (p = 0.004)

There were fewer acute (27% vs. 40%) and late toxicities (14% vs. 24%) in preoperative-treatment group

WITH THIS EVIDENCE PRE OP CHEMO RADIATION HAS BECOME THE STANDARD OF CARE FOR OPERABLE T3/T4/N+ RECTAL CANCERS

Locally Advanced Rectal CancerClinical T4 tumors may not be resected completely due to tumor fixation.

Preoperative radiation treatment is recommended to facilitate curative resections

M.D. Anderson investigators demonstrated that preoperative chemotherapy and radiation therapy increased overall survival (80% vs. 60%), local control (95% vs. 66%), and the number of sphincter preserving procedures (35% vs. 7%) as compared to radiation alone

IORTPreoperative continuous infusion 5-FU plus 50.4 to 54 Gy of radiation was given followed by a 4- to 6-week break and surgery.

IORT-Ten to 12.5 Gy were given for complete resection

12.5 to 15 Gy for microscopic residual

17.5 to 20 Gy for gross residual disease.

No IORT was given if metastases were present at surgical exploration

if there were adequate margins >1 cm

if there was less than T4 disease.

IORT improves local control, especially with a gross total resection, but not survival for locally advanced rectal cancer

Adjuvant ChemotherapyAdjuvant chemotherapy is recommended for all patients with stage II/III rectal cancer

following neoadjuvant chemoRT/surgery regardless of the surgical pathology results

A recent systematic review and meta-analysis of 9785 patients with nonmetastatic rectal cancer from 21 randomized controlled trials from 1975 until March 2011

concluded that OS and DFS are improved with the addition of postoperative 5-FUbased therapy

Most of the support for use of FOLFOX or capecitabine as adjuvant chemotherapy in rectal cancer is an extrapolation from the data from colon cancer

The use of a shorter course of adjuvant FOLFOX in rectal cancer (ie, 4 months) is justified when preoperative chemoRT is administered.

Management of Metastatic DiseaseApproximately 50% to 60% of patients diagnosed with colorectal cancer will develop metastases

synchronous metastatic colorectal liver disease is associated with a more disseminated disease state and a worse prognosis

than metastatic colorectal liver disease that develops metachronously.

Factors associated with a poor prognosis in patients with colorectal cancerthe presence of extrahepatic metastases

the presence of more than 3 tumors

a disease-free interval of fewer than 12 months

retrospective analyses and meta-analyses have shown that patients with solitary liver metastases have a 5-year OS rate as high as 71% following resection.

CRITERIA FOR RESECTABILITY OF METASTASES AND LOCOREGIONAL THERAPIES WITHIN SURGERYHepatic resection is the treatment of choice for resectable liver metastases from colorectal cancer.

Complete resection must be feasible based on anatomic grounds and the extent of disease;

maintenance of adequate hepatic function is required

The primary tumor must have been resected for cure (R0).

There should be no unresectable extrahepatic sites of disease.Plan for a debulking resection (R1/R2 resection) is not recommended.

Patients with resectable metastatic disease and primary tumor in place should have both sites resected with curative intent.

These can be resected in one operation or as a staged approach

RADIOTHERAPY

INDICATIONST3/T4 lesion

Node positive disease

Inoperable disease

Palliation of symptoms

TARGET VOLUME External-beam treatment portals for rectal carcinoma should always encompass the sites at greatest risk:

The presacral space

the primary tumor site, and the perineum (for post-APR cases)

The mesorectal and lateral lymph nodes and internal illiac are included in all patients

The external iliac nodes should be covered for T4 lesions.

The inguinal lymph nodes may be included

if tumour invades the lower third of the vagina

if there is major tumour extension into the internal and external anal sphincter

RADIATION TECHNIQUESPatients may be treated supine or prone

though placing the patient prone with a belly board may help move small bowel out of the pelvis.

A rectal marker or rectal contrast can help delineate the location of the tumor

wire perineal scar if present

small bowel contrast

Belly board

Fields2 field technique

3 field

4 field

Conventional Field bordersWhole pelvic field:A: Posterior-anterior Superior border: L5-S1 junction Distal border: 3cm below the primary tumor or at the inferior aspect of the obturator foramina, whichever is the most inferior Lateral borders: 1.5cm lateral to the widest bony margin of the true pelvic side walls.

B: Laterals Anterior border: T3 disease: Posterior margin of the symphysis pubis (to treat only the internal iliac nodes). T4 disease: Anterior margin of the symphysis pubis (to include the external iliac nodes

Posterior border: 1 to 1.5cm behind the anterior bony sacral margin

After an abdominoperineal resection:A:Wire the perineal scar and create a 1.5-cm margin beyond the wire in all fields.

Boost field:A: Treat the primary tumor bed plus a 3-cm margin (not the nodes).

Fig B: For a T4N1M0 rectal cancer 8cm from the anal verge. Since the tumor was a T4, the anterior field is at the anterior margin of the symphysis pubis (to include the external iliac nodes).Fig A: Treatment fields after a low anterior resection for a T3N1M0 rectal cancer 8cm from the anal verge. The distal border is at the bottom of the obturator foramen and the perineum is blocked. Since the tumor was a T3, the anterior field is at the posterior margin of the symphysis pubis (to treat only the internal iliac nodes).

Fig C: Treatment fields following an abdominoperineal resection for a T4N1M0 rectal cancer 2cm from the anal verge, because the tumor was a T4, the anterior field is at the anterior margin of the symphysis pubis (to include the external iliac nodes). Since the distal border is being extended only to include the scar and external iliac nodes, the remaining normal tissues can be blocked

Isodose curves for 3 field

Isodose curves for 4 field

3 D CONFORMAL RT

CT based treatment planning is preferred to ensure adequate coverage of the tumor and regional nodes and improve dose homogeneity

Planning CT should be taken from the level of mid abdomen (L1) to level of mid thigh with 5mm cut

Iv, rectal and bowel contrast will clearly defining target as well as critical structures

Fusion of the treatment planning CT with other imaging modalities MRI or PET may also help identify the tumor location

The GTV includes all gross tumour seen on the planning CT scan with reference to information from diagnostic endoscopy, MRI and DRE

Any involved lymph nodes, extrarectal extension, or extranodal deposits seen on MRI should be included

CTV should include peri-rectal, pre-sacral, internal iliac regions

RTOG GUIDELINESThe caudad extent of this elective target volume should be a minimum of 2 cm caudad to gross disease, including coverage of the entire mesorectum to the pelvic floor

The posterior and lateral margins of CTV should extend to lateral pelvic sidewall musculature or, where absent, the bone

Anteriorly, the group recommended extending 1 cm into the posterior bladder, to account for day-to-day variation in bladder position.

The recommended superior extent of the peri-rectal component

the rectosigmoid junction or 2 cm proximal to the superior extent of macroscopic disease in the rectum/peri-rectal nodes.

To include illiac vessels it should be kept at L5/S1 JUNCTION

Margin around blood vessels:

The group recommended a 7-8 mm margin in soft tissue around the external iliac vessels

but one should consider a larger 10+ mm margin anterolaterally IF nodes are identified in this area

BOOST VOLUMEThe group did recommend that any boost clinical target volumes extend to entire mesorectum and presacral region at involved levels

including ~2 cm cephalad and caudad in the mesorectum and ~2 cm on gross tumor within the anorectum.

PTV margin should be ~0.7 to 1.0 cm, except at skin

Techniques to Decrease Radiation Toxicity in Small BowelHigh-energy (>6MV) linear accelerators.

Treatment 5 days per week and all fields each day.

Port films once per week or more often if clinically indicated

Pelvic field: multiple-field technique (posterior-anterior plus laterals or posterior-anterior-anterior-posterior plus laterals) is recommended.

Boost field: opposed laterals.

Computerized dosimetry optimizing between minimizing the lateral hot spots and small bowel dose and increasing the homogeneity within the target volume

In thin patients, a combination of 6MV for the posterior fields and higher-energy photons for the lateral fields may result in more homogeneous dosimetry.

Shaped blocks and, if needed, wedges on the lateral fields.

Small bowel contrast. Shield as much small bowel as possible in the lateral parts

Rectal contrast. Barium sulfate is injected with a Foley catheter. A wire is placed on the catheter to indentify the anal verge

Prone position.

Full bladder, only if it does not make the patient so uncomfortable as to cause movement.

The entire perineum can be blocked after a low anterior resection

Immobilization molds (belly boards) and abdominal wall compression may be helpful

Intensity-Modulated Radiation Therapymay offer the potential to reduce toxicity

but there are no set standards regarding its use

Different IMRT volumebased dose constraints have been proposed for bowel and bladder, but there is no set consensus.

IMRT-based sparing of the iliac crests may also reduce bone marrow toxicity

Currently, IMRT is not recommended for routine use.

IMRT can be used in re irradiation for recurrence

endocavitary radiation therapy.T1 or T2 tumors less than 3 cm not poorly differentiatedwith no evidence of nodal involvement.

Patients are treated with a special low energy x-ray machine (50 kVp) that is attached to a rigid endoscopic-type device that can be placed in the rectum directly over the tumor.

As the opening of the applicator is 3 cm, it is difficult to treat tumors larger than this.

Patients typically receive four treatments of 2,500 to 3,000 cGy each with 2 to 3 weeks between treatments to allow for tumor regression.

Although the total dose is extremely high, the minimal penetration of the radiation beam protects the underlying normal tissue.

Local control results with this approach have been very good in properly selected patients

but specialized equipment is required (which is not generally available)

less pathological information is obtained than after a local excision.

This approach is rarely used at the present time

DosePreoperative radiotherapyShort course: 25 Gy in 5 daily fractions of 5 Gy given in 1 week.Long coursePhase 145 Gy in 25 daily fractions of 1.8 Gy given in 5 weeks.Phase 2 5.4 in 3 daily fractions of 1.8 Gy

Postoperative radiotherapyPhase 145 Gy in 25 daily fractions of 1.8 Gy given in 5 weeks.Phase 25.49 Gy in 35 daily fractions of 1.8 Gy.

Adverse effectsAcute complications

diarrhea and increased bowel frequency (small bowel)

acute proctitis (large bowel)

thrombocytopenia, leukopenia, and dysuria are common during treatment.

These conditions are usually transient and resolve within a few weeks following the completion of radiation.

In the small bowel, loss of the mucosal cells results in malabsorption of various substances, including fat, carbohydrate, protein, and bile salts.

The bowel mucosa usually recovers completely in 1 to 3 months following radiation.

Management usually involves the use of antispasmodic and anticholinergic medications.

Delayed complicationsoccur less frequently, but are more serious.

The initial symptoms commonly occur 6 to 18 months following completion of radiation.

persistent diarrhea and increased bowel frequency

proctitis, small bowel obstruction (SBO) not requiring surgery,

perineal and scrotal tenderness,

delayed perineal wound healing

urinary incontinence

bladder atrophy and bleeding.

Injury to the vascular and supporting stromal tissues is the presumed pathophysiologic condition

126