Surgical Staging and Neoadjuvant Therapy in Esophageal Cancer
February 1, 2002 5 minutes read
Surgical Staging and Neoadjuvant Therapy in Esophageal Cancer
Abstract & Commentary
Synopsis: Forty-five surgically staged patients with esophageal cancer who received preoperative chemoradiotherapy were studied. Although pretreatment nodal status predicted response to therapy, the post-treatment pathologic findings were correlated with survival. The entire group had a 3-year survival of 34%. There were no 2-year survivors if the post-treatment lymph nodes had residual cancer.
Source: Suntharalingam M, et al. Cancer J. 2001;7: 509-515.
Suntharalingam and associates present a large series with long-term follow-up of patients with surgically staged esophageal cancer who were treated with chemoradiotherapy (CRT) followed by definitive surgery. Forty-five patients were identified retrospectively who had undergone pretreatment surgical staging (PTSS) with a thoracoscopy and/or laparoscopy. The thoracoscopy included routine biopsies of regional nodes, and the esophagus was inspected for localized extension, which would be deemed unresectable. Laparoscopy included sampling of regional nodes and inspection of the liver. There were 15 node-negative and 30 node-positive patients.
Chemotherapy consisted of 2 4-week cycles of 5-FU (1000 mg/m2/d for 96 hours) and cisplatin (100 mg/m2, day 1). Concurrent radiation was delivered to the primary tumor and only those nodal areas proven to be involved by pathologic staging. The treatment delivered 39.6 Gy at 1.8 Gy per fraction, followed by a 10.8 Gy boost to the gross tumor volume. With just 2 exceptions, surgery was performed via a transthoracic approach (Ivor-Lewis esophagectomy) that included complete regional lymph node dissection.
The pretreatment nodal status was the only significant predictor of response to CRT. For example, a pathologic complete response (pCR) was found in 59% of node-negative patients (sterilized tumor bed) and 14% of node-positive patients (sterilized tumor bed and nodes). No difference between squamous cell carcinoma and adenocarcinoma emerged.
The 15 node-negative patients had the best median survival of 35 months. Sixty-eight percent of node-positive patients had no evidence of nodal disease after CRT resulting in a median survival of 17 months (with a 40% survival at 3 years). Unfortunately, the remaining node-positive patients with residual microscopic nodal involvement had a median survival of 5 months (with no 2-year survivors). Therefore, the most important predictor of survival turned out to be the nodal status at the time of esophagectomy.
Comment by Kenneth W. Kotz, MD
There have been at least 46 nonrandomized and 6 randomized trials of preoperative CRT in esophageal cancer.1 Three of the 6 randomized trials showed a benefit in either overall or disease-free survival.1,2 Despite provocative data, as discussed by Dr. Morris in the November 2001 issue of Clinical Oncology Alert,3 the definitive study proving superiority of any approach over surgery alone in esophageal cancer has not been performed.
The study by Suntharalingam et al is interesting because all patients were staged surgically. However, because "the vast majority of node-positive patients were discovered laparoscopically" (data not provided), the node-positive patients in this study might represent a population with a different prognosis than other series in which node-positive patients were detected radiographically. Furthermore, because initial esophagectomy was not performed, the false-negative rate associated with PTSS is undetermined. Unfortunately, even though all patients were also staged with CAT scans, EGD with ultrasound, and where indicated, MRI and bronchoscopy, Suntharalingam et al do not report either the correlation with the PTSS or the radiographic response rate.
One of the important conclusions by Suntharalingam et al is that "trimodality therapy offers patients with esophageal cancer an opportunity for long-term survival." Although lymph node status was the strongest predictor of survival, it is not reported whether node-positive patients with a pCR fared better than those patients who, after CRT, had negative nodes but persistent disease in the esophagus. Nevertheless, their conclusion is supported by a 3-year survival of 34% for the entire study group. On the other hand, the subgroup with persistent nodal involvement had no 2-year survivors. Although the numbers are small, Suntharalingam et al state "one could make a strong argument" to abort the esophagectomy if persistent nodal disease is discovered.
Another conclusion reached by Suntharalingam et al is that "pretreatment surgical staging provides useful information that can help in the selection of appropriate patients for aggressive therapy." For example, the PTSS was used to tailor the design of the radiation fields. While it seemed reasonable to cover only the pathologically involved nodal regions, there is no evidence that this is superior to standard empirically derived radiation fields or that it ultimately results in less toxicity. In addition, although termed "minimally invasive surgical staging," all patients required chest tubes and an average 3-day hospital stay with 1 pneumothorax requiring a prolonged chest tube.
Did the PTSS really help in selecting patients for trimodality therapy? The 45 patients identified for this study came from a cohort of 72 patients considered for trimodality therapy. Only 2 of these 72 patients were found to be unresectable based on PTSS, both having radiographically undetectable liver metastases. Inoperable esophageal cancer patients can also be identified by PET scans4, which have been shown to correlate with response to therapy as well as survival.4,5 In fact, PTSS does not seem to affect decision making. First, PTSS does not identify a subset of patients in whom preoperative CRT is either required or can be avoided. Second, the post-treatment pathologic findings seem to be most predictive of prognosis.
The role of neoadjuvant therapy in esophageal cancer remains controversial. It has been reported that a positive biopsy, in the absence of an endoscopically visible lesion, almost always corresponds to an intramucosal tumor without nodal metastases.6 These patients may be best served by a vagal-sparing or simple transhiatal esophagectomy6 and thus may not require CRT. On the other hand, operable candidates whose tumors are not technically resectable may benefit from the downstaging that occurs with preoperative CRT.2 For all others, preoperative CRT followed by esophagectomy is an option for medically fit patients, although esophagectomy alone must be presented as a treatment choice.
References
1. Geh J, et al. Br J Surg. 2001;88:338-356.
2. Green R, et al. Cancer Control. 1999;6:43-52. Also available online: http://www.moffitt.usf.edu/pubs/ccj/v6n1/article4.html
3. Morris A. Clinical Oncology Alert. 2001;16:81-84.
4. Downey R, et al. Proceedings ASCO 2001; Abstract #503.
5. Flamen P, et al. Proceedings ASCO 2001; Abstract #504.
6. Peters J. ASCO 2000 .Clin Practice Forum Book. 83-87.
Dr. Kotz, Hanover Medical Specialist, Wilmington, NC.
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