The number of metastases and its influence on outcome: editorial comment.

The number of metastases is an important prognostic factor. Because of the discrepancy between what is seen radiographically and what is found at surgery, it is important to distinguish between the number of nodules seen preoperatively and the number of metastases found pathologically in the resected specimens. Unfortunately, most of the reported data define the number of resected metastases and not the number of imaged nodules. There is ample evidence that the fewer the number of metastases present, the better the postresection survival.1–7 Many studies have reported that the 5-year survival of patients with only one metastasis identified at surgery was markedly better than that of patients who were found to have multiple metastases (average, 47% versus 17%; range, 35– 53% versus 8–26%).3–7 The International Registry study8 found that the 5-year survival of patients with one metastasis was better than that of patients with two to three metastases, who, in turn, survive longer than the patients with four or more metastases (5-year survival 43% versus 34% versus 27%, respectively). However, at 15 years, there was no difference among patients with more than one metastasis, and only those with a solitary metastasis exhibited better survival. When outcomes in the Registry data were corrected for the influence of other prognostic factors, independent prognostic significance was associated primarily with the presence of only one pulmonary metastasis, whereas the number of metastases more than one had little importance.8 There does not seem to be a threshold number of metastases found intraoperatively above which resection becomes futile. In the past, some surgeons limited their resections to less than or equal to four lesions, because it was felt that a number greater than this made the patient’s disease unresectable.9 One study suggested that the patients with more than six metastases found intraoperatively were likely to be unresectable,10 but it reported that the 5-year survival of such patients was 20% (compared with nearly 40% in patients with six or fewer metastases). The International Registry found a 5-year survival of 26% in patients with four or more lesions who underwent complete resection.8 Another study involving 44 patients (with various cancer types) who underwent resection of eight or more metastases found no significant survival difference compared with 412 patients with fewer than eight nodules (5-year survivals of 28 and 34%, respectively).11 The survival rates in these studies in patients in whom multiple metastases were resected are high enough to justify the procedure. Thus, there seems to be no reason to abort a metastasectomy operation no matter how many metastases are found intraoperatively as long as a complete resection can be accomplished and the patient can tolerate the procedure. Anecdotally, up to 117 metastases have been resected (in multiple operations) in a patient with soft tissue sarcoma with no further recurrences 6 1⁄2 years after the last resection.11 The important clinical question is whether patients in whom resection is not warranted can be identified preoperatively. Patients with a single pulmonary nodule (identified preoperatively) have been shown to have better survival than patients with multiple nodules seen preoperatively.5,12 The studies involving the patients with sarcomas have found an average 5-year survival of 34% (range, 15–47%) among patients with less than or equal to 4 (or sometimes less than or equal to three or five) nodules, whereas the average of 5-year survival was 2% (range, 0–8%) among patients with more than four preoperatively identified nodules.13–16 Another study involving 417 patients with renal metastasis found that the chance of an incomplete resection was approximately 80% with more than or equal to six versus 20% with less than or equal to 3 preoperatively identified nodules.17 However, many studies have reported a 5-year survival of approximately 20 to 25% in patients with more than four nodules as counted postoperatively.8,18,19 This discrepancy in results makes it unclear whether a threshold number of lesions can be defined above which metastasectomy seems futile, provided a complete resection is anticipated.