ANTI TUMOUR TREATMENTAdjuvant therapy of resectable rectal cancer
Introduction
There are two conventional treatments for clinically resectable rectal cancer. The first is surgery and, if the tumor is T3 and/or N1–2, this is followed by postoperative combined modality therapy (1). If the tumor on ultrasound assessment is classified as T3 or clinically staged as T4 then preoperative combined modality therapy followed by surgery and postoperative chemotherapy is the alternative approach (2).
Section snippets
Postoperative therapy
The NCI Consensus Conference concluded in 1990 that combined modality therapy was the standard postoperative adjuvant treatment for patients with T3 and/or N1–2 disease (1). Pelvic radiation therapy decreases local recurrence but does not improve survival. As would be predicted, randomized data do not reveal a survival advantage of pelvic radiation plus elective para-aortic and liver radiation versus pelvic radiation alone (3).
For patients treated with postoperative combined modality therapy
Are there patients who do not require postoperative adjuvant therapy?
There are retrospective data that suggest that there may be a subset of patients with T3N0 disease who do not require adjuvant therapy, as well as some patients with Stage I disease that should be considered for adjuvant therapy. Retrospective trials examining patients at both the MGH (17) and MSKCC (18) have identified favorable subsets of patients with T3N0 disease who, following surgery alone, had a 10-year actuarial local recurrence rate of <10%. These results need to be confirmed in a
Preoperative therapy
Preoperative therapy (most commonly combined modality therapy) has gained acceptance as a standard adjuvant therapy. The potential advantages of the preoperative approach include decreased tumor seeding, less acute toxicity, increased radiosensitivity due to more oxygenated cells, and enhanced sphincter preservation (2). The primary disadvantage of preoperative radiation therapy is the possible over treatment of patients with either early stage (T1–2N0) or undetected metastatic disease.
Sphincter function
Sphincter preservation without good function is of questionable benefit. In a series of 73 patients who underwent surgery, Grumann and associates reported that the 23 patients who underwent an APR had a more favorable quality of life compared with the 50 who underwent a low anterior resection (36).
Although preoperative combined modality therapy may adversely effect sphincter function, the impact is probably less than postoperative combined modality therapy (37). In four of the seven
Randomized trials
Three randomized trials of preoperative versus postoperative combined modality therapy for clinically resectable, T3 rectal cancer have been developed. Two are from the United States (INT 0147, NSABP R0-3) and one from Germany (CAO/ARO/AIO 94). All three use conventional doses and techniques of radiation therapy and concurrent 5-FU based chemotherapy and require a preoperative clinical assessment declaring the type of operation required. Unfortunately, low accrual has resulted in early closure
Response of the primary tumor
Although some series show no correlation (38), most series suggest that there is improved outcome with increasing pathologic response to preoperative therapy [39], [40], [41], [42]. Analysis of biopsies examining selected molecular markers such as c-K-ras (43), thymidylate synthase (44), p27kip1 (45), p53 [46], [47], [48], apoptosis [49], [50], and Ki-67 (51) have had varying success in helping to select patients who may best respond to preoperative therapy.
In one series the value of radical
The impact of total mesorectal excision on adjuvant therapy
Some physicians contend that adjuvant therapy is not necessary if patients undergo resection with a TME. In one series, TME, which involves sharp dissection around the integral mesentery of the hind gut, decreased the local recurrence rate to 5% (57). These data must be interpreted with caution for a number of reasons. First is selection bias. TME allows the identification and exclusion of patients with more advanced disease as compared with patients treated in the adjuvant trials in which more
Alternative radiation therapy approaches
Various fractionation strategies have evolved with the goal of enhancing tumor cell damage by radiation without augmenting normal tissue injury. The major limitation of accelerated hyperfractionation is acute normal tissue toxicity. However, late effects should be the same as or, more likely, less than in conventional fractionation schemes.
There are limited data on the use of twice a day (BID) radiation therapy in the pelvis. In a phase I/II trial from the RTOG, 54 patients with advanced
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2009, Surgical Clinics of North AmericaCitation Excerpt :Encouraged by the European data, interest increased in the United States to study the benefits of neoadjuvant chemoradiation in the preoperative setting. This approach was attractive because of several theoretic benefits, such as enhanced radiosensitivity, increased sphincter preservation rates, improved likelihood of resection, and less acute and late toxicity.173–175 Some of these potential benefits were confirmed in early trials by Willet and colleagues,176 who showed down-staging in 31% of patients, and Minsky and colleagues177 who illustrated a 90% sphincter preservation rate in patients initially believed to require APR.
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