Matched Patients In A Teaching Hospital’s Clinico-‐Pathological Database
INTRODUCTION
One of the continuing dilemmas for gastrointestinal oncologists is the question of optimal adjuvant treatment for patients with locally advanced rectal cancer. This may have arisen from improvements in surgery, radiotherapy and chemotherapy while information relating to their combined use has lagged behind. In surgery, there has been widespread adoption of precise anatomical mobilisation of the rectum by sharp dissection (Total Mesorectal Excision (TME) surgery) together with the impact of surgical sub specialization. The ensuing low rates of local recurrence and improved survival from individual surgical units have prompted some colorectal surgeons to question the routine use of adjuvant therapies.
1-‐3 In radiotherapy, improvements in planning and scheduling have occurred, including the
introduction of short and long course neoadjuvant protocols in an attempt to reduce the frequency of small bowel toxicity, diarrhoea and incontinence that complicated earlier post-‐ operative adjuvant radiotherapy regimens. 4, 5 Chemotherapy for colorectal cancer has seen the development of new infusional schedules of 5-‐fluorouracil and the introduction of new drugs including oxaliplatin, irinotecan, capecitabine and the molecular targeted therapies, bevacizumab, cetuximab and panitumumab. However, their optimal use in rectal cancer patients, especially in the adjuvant and neoadjuvant settings in combination with radiotherapy remains uncertain. Furthermore, identification of optimal adjuvant chemotherapy protocols for rectal cancer has been complicated by the fact that rectal cancer patients have been excluded from most large international adjuvant studies.
Despite these uncertainties, it has been clearly established in large prospective randomized studies that adjuvant chemoradiation reduces local recurrence and produces small increments in survival for those patients with locally advanced disease (T3 tumours and locally involved lymph nodes). 6, 7 Short course neoadjuvant radiotherapy in selected patients
has been shown to be as effective as longer courses of radiotherapy. 8, 9 However, there are
groups of rectal cancer patients for whom radiation might not be necessary (due to the site of the tumour 10, small primary tumour size or small numbers of involved lymph nodes not
recognized pre-‐operatively), or actually contraindicated (because of prior therapy for other diseases or local surgical issues). Such patients might still benefit from effective systemic adjuvant therapy and there are some data to support the use of adjuvant chemotherapy alone. 11-‐13 For example, in the Japanese National Surgical Adjuvant Study of Colorectal
Cancer, patients who had undergone standardized mesorectal excision with selective lateral pelvic lymphadenectomy for stage III rectal cancer were randomly assigned to receive postoperative adjuvant oral uracil-‐tegafur for one year or no further treatment. 14 Radiotherapy was not used either pre-‐ or postoperatively. The 3-‐year overall survival rate in the treated group was 91% compared to 81% in the untreated group (p = 0.0048).
Another issue that has been difficult to control for in adjuvant studies in rectal cancer has been the quality of the surgery. It has been recognized that there are major differences in recurrence rates and outcomes between individual surgeons and different surgical units based on experience and training of the operator. Attempts have been made to reduce variability in surgical quality through the use of surgical trainers and mentors 15, 16 prior to
and during randomised trials, and by undertaking audit of pathology specimens during such studies and providing feedback to the surgeons. 17, 18 However, such capacity has not been
We evaluated the efficacy of chemotherapy alone in a cohort of patients who had a resection for stage C (III) rectal cancer at Concord Hospital and for whom information had been recorded in a prospective hospital registry of colorectal cancer. Concord Hospital has a large colorectal unit with a clinicopathological database that has accumulated the outcomes of all resected patients with over 95% accuracy since 1971. In addition, since 1981 all resections have been performed by a small group of surgeons using a standardized operative technique. 3 Surgical quality was also assessed by the involvement of a small number of
specialist colorectal pathologists during that same period. The unit was slow to adopt routine use of adjuvant radiotherapy and used adjuvant chemotherapy only for high risk stage C (III) rectal cancer patients as positive results accrued for stage C (III) colon cancer patients. 19, 20
The aim of the present study was to compare patients who had received adjuvant chemotherapy with patients earlier in the series before chemotherapy was introduced in order to evaluate the benefits of postoperative adjuvant chemotherapy in this patient group.
PATIENTS AND METHODS
The Concord Hospital prospective registry of consecutive patients having a resection for colorectal cancer 21, 22 has the approval of the South Western Sydney Health Area Ethics Committee. Treatment of patients was discussed in regular multidisciplinary meetings comprising surgeons, pathologists, oncologists, nurses and allied health providers. Additional information on patients receiving adjuvant chemotherapy in the period from May 1992 to December 2007 was compiled retrospectively from patient records by an oncologist (PK) and a surgeon (PC).
All resections since 1981 were performed by colorectal surgeons along anatomical planes following a standardized technique as described previously.3 Co-‐morbidity and