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Editorial |
1 Department of Surgery, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Rochester, New York 14642
2 Department of Surgery, Division of Surgical Oncology, Rochester General Hospital, 1425 Portland Avenue, Rochester, New York 14621
Correspondence: Address correspondence and reprint requests to: Stephen E. Ettinghausen, MD, Department of Surgery, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Rochester, NY 14642; E-mail: stephen.ettinghausen{at}viahealth.org.
The optimal treatment of gastric adenocarcinoma continues to be a challenging clinical problem. Resection alone is associated with a high rate of relapse and a 10-year survival rate ranging between 3% and 42%, depending on stage.1 As a result of the generally poor outcomes after operative therapy, several authors have focused their efforts on more accurate preoperative staging and on the identification of preoperatively recognizable factors that may predict either better or worse survival. The goal of these studies is to select the most appropriate therapy for patients with gastric cancer according to their stage of disease and relative risk of death from malignancy. Consequently, for patients expected to have a poorer prognosis after curative resection alone, gastrectomy with aggressive multimodal therapies combining neoadjuvant or adjuvant strategies may offer better outcomes. For patients treated with preoperative chemotherapy protocols, an additional advantage is gained in which resection may be used selectively for patients most likely to benefit from an operation, while laparotomy is avoided in patients who exhibit progressive disease due to a more biologically aggressive cancer.
In this issue of Annals of Surgical Oncology, Bentrem et al.2 evaluate the utility of cytological analysis of peritoneal washings as a means of pre-operatively identifying patients with gastric carcinoma who are at high risk for recurrent disease and decreased survival, even after curative resection. Using a prospectively maintained database, the authors analyzed factors predictive of outcome in 371 patients with gastric carcinoma who underwent diagnostic laparoscopy and peritoneal lavage cytology before R0 resection. Twenty-four patients (6.5%) were identified as having positive peritoneal cytology (3 [2%] of 152 with stage I disease, 6 [7%] of 90 with stage II disease, and 14 [11%] of 127 with stage III disease). Multivariate analysis identified preoperative T stage, preoperative N stage, primary tumor site, and peritoneal cytology status as the only significant independent predictors of survival. Positive cytology was the most significant predictor, correlating with a median survival of 14.8 months, versus 98.5 months for patients with negative cytology (P < 0.001).
Other groups have described the correlation between positive peritoneal cytology and poor outcome according to postoperative staging after R0 resection for gastric cancer.3,4 Because free cancer cells in the peritoneal cavity represent stage IV disease, knowing this information before surgery would help to identify patients who would likely not benefit from curatively intended resection alone. In turn, this population of high-risk patients would best be treated by incorporating other treatment options, such as neoadjuvant, adjuvant systemic, or intraperitoneal chemotherapeutic regimens.
If diagnostic laparoscopy and analysis of peritoneal cytology are to be considered a routine part of the preoperative work-up, then the question remains: on whom should it be performed? Clearly, use of this invasive staging protocol in all patients with gastric cancer adds the risks of general anesthesia, bleeding, and bowel injury, as well as unjustifiable additional cost (particularly in patients with early-stage disease). The current study by Bentrem et al.2 and those by other authors demonstrate a correlation between an advanced stage of disease and the prevalence of positive peritoneal cytology.3,4 Although the current study found an overall 6.5% prevalence of positive peritoneal cytology in its patient cohort, the prevalence is higher, at 10%, in patients with T3 or T4 tumors.2 Similarly, the study by Bonenkamp et al.3 of the Dutch Gastric Cancer Trial quotes an overall rate of positive peritoneal cytology of 5.7% in the 457 patients studied, with a prevalence of 12% in patients with serosal invasion. Finally, Burke et al.4 demonstrated an overall 4% rate of positive peritoneal cytology in patients undergoing R0 resection of gastric cancer but found a 10% rate in patients with T3 or T4 disease. If immunohistochemistry or polymerase chain reaction is added to conventional staining methods used to evaluate the peritoneal washings, the number of positive specimens increases.5,6
How, then, are patients with gastric cancer best staged before surgery? Once a diagnosis has been made, computed tomography has been the cornerstone for the initial evaluation of the primary tumor, as well as for documentation of malignant ascites or metastatic disease. Endoscopic ultrasound has become a valuable tool for assessing the depth of tumor penetration, or T stage, and has an 83% to 95% accuracy for identifying T3 or T4 tumors before surgery.7 Combined with computed tomography and endoscopic ultrasound, diagnostic laparoscopy and analysis of peritoneal cytology only for patients with tumors of increased depths of penetration (and, thus, at increased risk of positive peritoneal cytology) will have the highest yield in identifying patients with stage IV disease who would not benefit from immediate gastrectomy alone but, rather, who may be better suited for treatment with neoadjuvant or adjuvant chemotherapy and resection.
The conclusions of Bentrem et al.2 raise another interesting question: namely, what is the pattern of recurrence for poor-risk patients with positive peritoneal cytology? One could hypothesize from their data that peritoneal recurrence must be extremely high in this patient group. How this recurrence profile compares with that of patients who have similar T and N stages but negative peritoneal cytology is less clear. In general, the rate of peritoneal recurrence is high in gastric cancer patients after curative resection,8,9 with an incidence of 46% to 54%.
Still unconquered, however, is the major hurdle in this disease, namely, the identification of regimens with truly significant efficacy against micrometastatic disease at local, regional, peritoneal, and distant sites. Several different therapeutic strategies aimed primarily at peritoneal disease have been explored, including intraperitoneal chemotherapy given before, during, and after surgery.10–12 Recently, a neoadjuvant regimen with irinotecan and cisplatin demonstrated significant efficacy in an initial trial for the treatment of patients with locally advanced gastric cancer.13 Finally, as progress is made in the identification of new drugs and in the elucidation of the most effective schedules for their delivery, then the utility of preoperatively identified poor prognostic variables, such as positive peritoneal cytology in otherwise resectable gastric cancer, will become even more important.
Received for publication January 12, 2005. Accepted for publication February 3, 2005.
REFERENCES
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