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Conservative Management of Rectal Cancer With Local Excision and Adjuvant Therapy

Conservative Management of Rectal Cancer With Local Excision and Adjuvant Therapy

ABSTRACT: The standard surgical treatment of distal, resectable, invasive rectal cancers is an abdominoperineal resection or a low anterior resection. Given the morbidity associated with these standard treatments and the frequent need for postoperative adjuvant therapy, the use of a more conservative approach, such as local excision with adjuvant therapy as primary therapy for selected cases of rectal cancer is appealing. Data from single-institution series as well as recent data from prospective, multi-institutional studies, suggest that local excision with adjuvant therapy is a reasonable alternative to radical surgery in selected patients. Local excision alone is acceptable treatment only for T1 tumors without adverse pathologic features, while local excision with adjuvant therapy is an alternative treatment for T1 tumors with adverse pathologic features and T2 tumors. Some series suggest that preoperative therapy with local excision may be a possible treatment for selected T3 tumors; however, the high local failure rates seen in T3 tumors treated with local excision and postoperative therapy cautions against this approach. Functional results with local excision are generally good, and postoperative morbidity and mortality is acceptable. In summary, the results of local excision and radiation therapy are encouraging. Randomized trials are needed to determine whether this approach has local control and survival rates comparable to those of radical surgery. [ONCOLOGY 15(4):513-528, 2001]

Introduction

The standard surgical treatment
for cancer of the rectum is primarily abdominoperineal resection or low anterior resection. If the tumor is
transmural or lymph node positive, adjuvant therapy with fluorouracil
(5-FU)-based chemotherapy and radiation is indicated.[1,2] Standard management
of lesions closer to the dentate line often mandates use of abdominoperineal
resection, due to the need for an adequate distal margin. Depending on the exact
location, abdominosacral resection, stapled low anterior resection, or
proctectomy with coloanal anastomosis may be feasible in selected patients.[3,4]
These radical approaches can be associated with complications and functional
consequences.

Postoperative Complications
and Recurrence Patterns

In some series, postoperative complication rates range from 30%
to 46%, and postoperative mortality from 2% to 6%.[5,6] Neurogenic bladder with
inability to void is common after extensive pelvic dissection.[6] Sexual
dysfunction is also common, particularly in men. Retrograde ejaculation, related
to sympathetic nerve dysfunction, is seen in 15% to 100% of men. Erectile
impotence resulting from damage to the pelvic parasympathetic plexus is seen in
3% to 39% of men.[7-9] Even after a low anterior resection, up to 50% of
patients report decreased rectal sphincter function, and up to 30% report
urinary retention or sexual dysfunction.[9,10] Finally, the psychological and
social consequences of colostomy in patients who require it cannot be
underestimated.

With standard surgery for early-stage rectal cancer (T1/2, N0),
local recurrence rates range from 0% to 10%, and 5-year survival rates from 78%
to 100%.[11-14] Sticca et al evaluated 71 patients (T1: 20, T2: 51) with stage I
rectal adenocarcinoma who were treated with an abdominoperineal resection. At a
median follow-up of 81 months, the local control rate was 100% for T1 tumors,
and 90% for T2 tumors. Of the 7 recurrences, 2 were local, 4 were distant, and 1
was local and distant. For patients with T2 disease, the 5-year disease-free
survival rate was 88%.[13]

Willett et al reported the recurrence patterns of stage I rectal
cancer treated by abdominoperineal resection. The local control and disease-free
survival rates at 6 years were both 100% for 12 patients with T1 disease. For
the 52 patients with T2 disease, the local control and actuarial disease-free
survival rates were 84% and 80%, respectively.[14] These numbers represent the
standard to which any proposed conservative treatment must be compared. However,
functional outcome with conservative treatment approaches must be evaluated,
because a poorly functioning sphincter may have a more detrimental effect on
quality of life than a well-functioning colostomy.

Surgical Techniques

Local options for surgical management include transanal local
excision, transsacral excision (Kraske approach), transsphincteric resection
(Bevan or York-Mason approach), transanal endoscopic microsurgery, and
electrocoagulation. Transanal local excision should be performed as a
full-thickness excision where the perirectal fat serves as the deep plane of
dissection.

The Kraske excision is used for lesions too large or proximal
for transanal local excision, and allows for removal of some perirectal lymph
nodes. A perineal incision is made just above the anus, the coccyx is removed,
and the fascia is divided. The rectum is mobilized through this incision, and a
wide local excision or sleeve resection can be performed.

The transsphincteric procedure is identical to the Kraske
procedure, except that the anal sphincter is divided posteriorly in the midline.
The anus is reconstructed at completion of the operation, with little risk of
functional impairment.[15]

In transanal endoscopic microsurgery, an operating rectoscope is
used to perform a full-thickness disc excision of the rectum, with primary
closure. Fulguration is completed in multiple steps with the patient under
general or regional anesthesia, and involves charring of the tumor, then
scraping with a curette. There is a 10% to 20% risk of delayed hemorrhage due to
sloughing of the scar at 7 to 10 days.[16-21]

Full-thickness local excision is preferred over destructive
approaches because the complete specimen is available for assessment of depth of
invasion, margins, and pathologic features known to be prognostic for lymph node
involvement.

Selection Criteria

Local treatment has historically been applied to patients with
medical contraindications to radical surgery—for example, severe
cardiopulmonary disease or patient blindness (which makes colostomy care
difficult). More recently, the use of local treatment has been explored as an
alternative to abdominoperineal resection. Studies suggest that small (< 3
cm), exophytic, well-differentiated tumors limited to the submucosa warrant this
approach.

Local treatment approaches have also been used for selected
tumors invading the muscularis propria. Tumors that would be suitable for a
local approach should be chosen carefully, based on clinical, pathologic, and
radiologic factors.

Clinical Criteria

An evaluation of clinical criteria in the series examining local
excision is difficult due to variations in patient selection, the definition of
clinical and pathologic features, and length of follow-up. Moreover, the series
examining local excision alone were limited by the use of univariate analysis,
rather than multivariate analysis. It is, therefore, difficult to make
recommendations based solely on clinical criteria. However, tumors that are
small, mobile, and involve less than 40% of the circumference of the rectal wall
could most likely be excised with negative margins by a full-thickness,
nonfragmented excision.

Pathologic Criteria

The impact of various pathologic factors on local recurrence and
the overall outcome of rectal cancer has been studied extensively. Regional
lymph node metastases that are unrecognized at the time of local excision are
thought to account for the majority of local failures after conservative
treatment. Factors that are known to have an impact on the incidence of lymph
node involvement include the presence of high-grade features, lymphatic or
blood vessel invasion, colloid histology, or penetration of tumor through the
bowel wall.

Tumors without any of these features comprise only 3% to 5% of
all rectal cancers. These select cancers have a low enough incidence of local
failure (5% to 10%) and positive nodes (< 10%) so as not to require adjuvant
therapy.[20] However, once adverse pathologic features manifest or the tumor
invades the muscularis propria, the local failure rate approaches 20% and the
incidence of positive pelvic or mesorectal lymph nodes is 10% to 15%.[22]

Tumor Grade/Differentiation: Minsky et al retrospectively
studied various clinical and pathologic features in 168 patients who underwent a
potentially curative surgery for rectosigmoid or rectal cancer at the New
England Deaconess Hospital. They found that the incidence of positive lymph
nodes increased with the grade of adenocarcinoma. None of the
well-differentiated tumors had lymph node involvement, while 30% of moderately
differentiated, and 50% of poorly differentiated tumors had lymph node
involvement (P = .07).[23]

Brodsky et al also found that grade significantly affected the
incidence of lymph node metastases in 154 patients with pT1 or pT2 rectal cancer
treated by radical resection. The risk of lymph node metastases was 0% for
well-differentiated tumors, but rose to 24% for moderately and poorly
differentiated tumors (P = .04).[24]

Lymphatic/Blood Vessel Invasion: It is established that the
incidence of lymph node metastasis increases significantly with lymphatic or
blood vessel invasion. Investigators from Memorial Sloan-Kettering Cancer Center
analyzed 154 patients with pT1 or pT2 tumors and found that 17% of T1/T2 tumors
without lymphatic or blood vessel invasion had lymph node metastasis, while 31%
of T1/T2 tumors with lymphatic or blood vessel invasion had lymph node
metastases (P = .04). Furthermore, within the group of patients with T1 tumors,
0 of 15 without vascular invasion had lymph node metastases, while 3 of 9
patients with vascular invasion had lymph node metastases (P < .05).[24]

Margins: Adam et al evaluated 141 specimens from resections
thought by the surgeon to be curative. The closest point of the tumor to the
circumferential margins was measured microscopically, and any specimen with
tumor ≤ 1 mm from the circumferential margin of excision (25% of specimens) was
recorded as having positive margins. At a median follow-up of 5 years, the
authors found that local recurrence occurred in 78% of patients with involvement
of the circumferential margin, compared with 10% of those without such
involvement (P < .001).[25]

T Stage: Increasing T stage also significantly increases the
risk of lymph node metastasis. A study from Basingstoke District Hospital
evaluated 454 rectal excision specimens. Of 109 patients, 22 (20%) with tumor
confined locally to the bowel wall had metastases in local lymph nodes. Among 27
patients (11%) with tumors that did not penetrate the submucosa, 3 (11%) had
lymph node metastases (P = .28).[26] Minsky et al also found that
increasing T stage was associated with increasing risk of lymph node metastases.
In their series, lymph node involvement was seen after radical surgery in 0% of
T1 tumors, 28% of T2 tumors, 36% of T3 tumors, and 53% of T4 tumors (P =
.04).[23]

Use of these pathologic criteria in selecting "early"
carcinomas of the rectum has been criticized. Nelson et al retrospectively
reviewed 76 cases of adenocarcinoma of the lower rectum treated by
abdominoperineal resection. They found that 50% of patients with tumors ≤ 4.0
cm had lymphatic invasion. Overall, 53% of patients who had well- or moderately
differentiated tumors had lymphatic metastases, and 25% of those with only
partial invasion of the muscular layer had lymphatic metastases. The authors
concluded that the commonly used criteria of size and histologic grade are
inadequate and do not allow confident selection of patients with lesions
suitable for local treatment.[27]

Recent data from Memorial Sloan-Kettering Cancer Center suggest
that the overall risk of lymph node metastasis in patients selected on the basis
of small (£ 4.0 cm) tumor size and early T stage (T1/T2) is 15% (T1:10%,
T2:17%). On subset analysis, while T stage, degree of differentiation, and
lymphatic vessel invasion influenced the risk of lymph node metastasis, only
blood vessel invasion reached statistical significance as a single predictive
factor of lymph node metastases (blood vessel invasion-negative = 13%; blood
vessel invasion-positive = 33%; P = .04). Even in patients in the
most favorable group (T1 cancers with no adverse pathologic features), 7% had
lymph node metastases.[28]

Other studies have confirmed that T1 and T2 tumors with
unfavorable histologic features have decreased rates of survival and local
control, whether treated by local excision or abdominoperineal resection.
Willett et al found that tumor size greater than 3 cm, high-grade histology,
invasion of the muscularis propria, vascular invasion, and positive margins were
associated with a local failure rate of at least 20%, as well as an increase in
distant metastases.[29,30] In summary, once adverse pathologic factors are
present (high grade, lymphatic or blood vessel invasion, colloid histology,
signet ring cell or tumoral invasion of the muscularis propria), local therapy
alone is inadequate.

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