First Site Of Metastasis Research Articles

Inhibition of VEGFR-3 Activation with the Antagonistic Antibody More Potently Suppresses Lymph Node and Distant Metastases than Inactivation of VEGFR-2

Lymph nodes are the first site of metastases for most types of cancer, and lymph node status is a key indicator of patient prognosis. Induction of tumor lymphangiogenesis by vascular endothelial growth factor-C (VEGF-C) has been shown to play an important role in promoting tumor metastases to lymph nodes. Here, we employed receptor-specific antagonist antibodies in an orthotopic spontaneous breast cancer metastasis model to provide direct evidence for the key role of VEGFR-3 activation in metastasis. Inhibition of VEGFR-3 activation more potently suppressed regional and distant metastases than inactivation of VEGFR-2, although VEGFR-2 blockade was more effective in inhibiting angiogenesis and tumor growth. Despite prominent proliferation, metastases were not vascularized in any of the control and treatment groups, indicating that the growth of metastases was not dependent on angiogenesis at the secondary site for the duration of the experiment. Systemic treatment with either VEGFR-2 or VEGFR-3 antagonistic antibodies suppressed tumor lymphangiogenesis, indicating that VEGFR-3 signaling affects the rate of tumor cell entry into lymphatic vessels through both lymphangiogenesis-dependent and independent mechanisms. Combination treatment with the anti-VEGFR-2 and anti-VEGFR-3 antibodies more potently decreased lymph node and lung metastases than each antibody alone. These results validate the concept of targeting the lymphatic dissemination and thereby very early steps of the metastatic process for metastasis control and suggest that a combination therapy with antiangiogenic agents may be a particularly promising approach for controlling metastases.

Variates of Survival in Metastatic Uveal Melanoma

The course and outcome of metastatic uveal melanoma are not well described. We evaluated the survival of our patients with metastatic uveal melanoma, described factors that correlated with survival, and evaluated the influence of screening tests on time of detection and survival. All patients with metastatic uveal melanoma seen at Memorial Sloan-Kettering Cancer Center between 1994 and 2004 were identified from our database. We recorded date of initial diagnosis, date of metastatic disease, date of last follow-up, site of the first metastasis, how the first metastasis was discovered, treatment, and outcome of therapy. The estimated median survival of the 119 patients analyzed was 12.5 months; 22% of patients were alive at 4 years. Five variates correlated independently with prolonged survival: Lung/soft tissue as only site of first metastasis, treatment with surgery or intrahepatic therapy, female sex, age younger than 60, and a longer interval from initial diagnosis to metastatic disease. Discovering metastatic disease in asymptomatic patients did not correlate with overall survival; 89% of patients had a single organ as the site of first metastasis. Although liver was the most common site, 39.5% of patients had nonliver sites, most commonly lung, as the first site of metastasis. A substantial subset of patients with metastatic uveal melanoma survive more than 4 years with metastatic disease. Data on variates of survival and site of first metastasis may guide strategies for screening patients, although our data failed to show a survival advantage in discovering asymptomatic metastatic disease.

Variates of survival for stage IV uveal melanoma

7536 Background: Systemic therapy of stage IV uveal melanoma (mel) is not thought to improve survival. In selected patients (pts), local therapy of metastases (mets) (e.g. surgery or intrahepatic therapy) can be associated with long-term survival. The natural history of stage IV mel is heterogeneous and not well-described. We were interested in describing the natural history and factors that correlate with long-term survival in the stage IV uveal mel pts seen at our institution. Methods: A retrospective analysis of the 119 stage IV uveal mel pts in the MSKCC mel database. We recorded dates of initial diagnosis, stage IV, last follow up, and death; site of 1st met, how the 1st met was discovered, treatment. Results: 40 pts were still alive at last follow up (median follow up of survivors = 8 months). Median overall survival was 12.5 months (95% CI 9.6–16.8). 22% were alive at 4 years. A novel observation was that 28% of the pts had lung/soft tissue only as the site of first metastasis. In a multivariate analysis, we found 3 variates that correlated independently with prolonged survival: Lung or soft tissue as only site of first metastasis (p=.03, HR 0.55, CI .32-.95), treatment with surgery or intrahepatic therapy (p=.005, HR 0.38, .22-.65), and time interval from diagnosis to stage IV uveal mel (p=.03). Whether stage IV mets were first discovered by screening tests (CT scans, blood tests routine physical exam) or by symptoms did not correlate with the likelihood of having surgery or with overall survival. Conclusions: Pts with lung/soft tissue only as the site of first metastasis, pts who are treated with local therapy (surgery or intrahepatic therapy), and pts with longer time interval from initial diagnosis to stage IV have longer survival after stage IV uveal mel is diagnosed. There appeared to be no survival advantage in discovering asymptomatic stage IV uveal mel. Hopefully this will change with improved systemic treatments. No significant financial relationships to disclose.

Primary High-Grade Osteosarcoma

The medical records of patients with high-grade osteosarcoma observed at the authors' institution between 1972 and 1999 were reviewed to study whether osteosarcoma in preadolescent patients has a different biology and a worse prognosis than in older patients. To assess epidemiologic differences, the first analysis evaluated 1,603 patients regardless of tumor stage and site and treatment received. In the second analysis, only 1,136 patients (317 preadolescent and 819 older patients) with nonmetastatic extremity osteosarcoma, treated with the same protocols of chemotherapy, were evaluated to assess differences in prognosis and in the pattern of relapse. Most preadolescents were female (56% vs. 44%, P < 0.0001), and most tumors were located in the extremity (95% vs. 5%, P < 0.001). The 5-year event-free survival (60% [95% CI 53-67%] vs. 58% [95% CI 46-63%]), the overall survival (67% vs. 65%), the rate of amputation (24% vs. 25%), time (21 vs. 22 months) and type of first relapse (systemic 98% vs. 95%, local 2.3% vs. 4.7%) the site of first metastases (pulmonary, 87% vs. 89%), and good histologic response to preoperative treatment (65% vs. 63%) were essentially the same. The authors concluded that there is no need to employ different therapies for the two groups.

The effect of ethnicity on presentation, pattern of metastasis, and survival in gastric adenocarcinoma at a single center

4016 Background: The effect of race/ethnicity in gastric cancer remains incompletely delineated. Methods: 1920 patients with gastric adenocarcinoma who were treated at MD Anderson Cancer Center from 1985–1999 served as the study cohort. Median survival duration was estimated by the Kaplan-Meier method. Cumulative survival was compared using the log-rank test. Self-identified race, AJCC stage, WHO histology, gastric subsite, age, and sex were entered into a Cox proportional hazards model for multivariate survival analysis. Results: 1352 patients (70%) were white/Caucasian; 301 (16%) were Latino; 163 (8%) were African-American; 81 (4%) were Asian; 19 (2%) were unknown. 63% were men. Gastric cancer location and stage varied by race (p<0.0005); Asians were more likely to have mid- or distal gastric involvement (62%, vs 42% for African-Americans, 18% for Latinos, 13% for whites), and less likely to have metastases (p=0.007) (AJCC Stage IV: 37% of Asians, 68% of African-Americans, 59% of Latinos, 56% of whites). Of patients who had their first site of metastasis to either liver or peritoneal cavity (n=808), Asians were more likely than other groups to have peritoneal rather than liver metastasis (p=0.001). White, Latino, and African-American patients had unadjusted median survivals less than half that of Asians (12.0, 10.8, and 10.5 months vs 26.7, respectively). After adjusting for demographic and tumor characteristics, compared to whites, Latinos had a similar risk of death (HR 1.08, 95% CI 0.91–1.28), while African-Americans had an increased risk (HR 1.29, 95% CI 1.04–1.59, p=0.021) and Asians had a decreased risk of death (HR 0.70, 95% CI 0.50–0.96, p=0.028). Conclusions: We report a large single-center experience with gastric adenocarcinoma in an ethnically diverse patient population. After multivariable analysis, Latinos have equivalent survival to whites, whereas African-Americans demonstrate decreased and Asian have increased survival compared to all other races. These differences were independent of stage, histology, tumor location, age, and gender. Factors contributing to these differences warrant further investigation. No significant financial relationships to disclose.

Metastatic pattern and survival in disseminated conjunctival melanoma: Implications for sentinel lymph node biopsy

Purpose To study the pattern of metastasis and overall survival in patients with disseminated conjunctival melanoma. Design Population-based, retrospective cross-sectional study. Participants Eighty-five Caucasian patients with primary malignant conjunctival melanoma diagnosed between 1967 and 2000. Methods Data were collected from the Finnish Cancer and Population Registries and all involved hospitals. The pattern (regional or systemic) and site of first metastasis were recorded. The time to first metastasis and survival by pattern were estimated by cumulative incidence analysis, which takes competing risks into account, and by Kaplan–Meier analysis, respectively. Main outcome measures Metastatic pattern, time to metastasis by pattern, overall survival. Results In 45% (95% confidence interval, 23%–68%) of 20 patients with metastasis, regional lymph node metastases were detected before systemic ones. Median times to initial regional and systemic metastasis were 2.3 and 3.4 years, respectively, and the median time from regional to systemic metastasis, 1.0 year. The 10-year cumulative incidence of initial regional metastasis was 0.11, and it tended to be higher for tumors more than 2 mm thick (0.18 vs. 0.05, P = 0.062). The corresponding incidence of initial systemic metastasis was 0.18, and it was higher for nonlimbal tumors (0.38 vs. 0.07, P = 0.00023) and for tumors more than 2 mm thick (0.28 vs. 0.06, P = 0.026). Overall survival was longer after initial regional metastasis than after systemic metastasis (30 vs. 8 months, P = 0.012). Conclusion Initial regional lymph node metastasis was as common as systemic metastasis, but initial lymph node metastasis was associated with better prognosis. Metastasis, especially initial regional lymph node metastasis, from limbal tumors and tumors less than 2 mm thick was rare. These patients may have less benefit from sentinel lymph node biopsy, a method that is currently under evaluation regarding its potential to improve survival.

Sentinel node biopsy as a tool for accurate staging of eyelid and conjunctival malignancies.

Sentinel lymph node (SLN) biopsy has emerged as a technique for accurate staging of solid tumors. This technique permits the detection of microscopic metastases in clinically negative regional lymph nodes and may be indicated for malignancies that have a propensity for regional nodal metastasis. With the exception of basal cell carcinoma, almost all malignancies of the eyelid and conjunctiva metastasize to regional lymph nodes as the site of first metastasis. The histologic status of the SLNs has been shown to be the most significant prognostic factor with respect to recurrence and survival in patients with cutaneous melanoma. The indications for and the feasibility of SLN biopsy for eyelid and conjunctival tumors and our experience with this technique are reviewed.

Patterns of regional and distant metastasis in patients with conjunctival melanoma: Experience at a cancer center over four decades

Objective The regional lymph nodes generally are believed to be the most common first site of metastasis for conjunctival malignant melanoma, but the pattern of nodal metastasis in this disease has not been well established. The goal of this study was to determine the frequency, location, and timing of regional lymph node metastasis in patients with conjunctival melanoma treated at one cancer center over four decades. Design Retrospective case series. Participants Twenty-seven patients. Methods The clinical records of 27 patients with conjunctival malignant melanoma were reviewed retrospectively. Main outcome measures The rates of local conjunctival recurrence, regional nodal metastasis, and distant metastasis were analyzed along with overall survival. The follow-up time ranged from 2.5 to 17 years (median, 6 years). Results Eleven patients (41%) experienced clinical regional lymph node metastasis 1.5 to 6.0 years (mean, 3.2 years) after the initial diagnosis. The involved lymphatics were the preauricular (parotid) nodes in 8 patients (73%), the submandibular nodes in 1 patient (9%), and the deeper cervical nodes in 2 patients (18%). In seven patients (26%), distant metastasis developed without evidence of prior or concurrent regional nodal disease. Patients in whom distant metastasis developed without clinical evidence of regional nodal involvement were more likely to have had local conjunctival recurrence ( P = 0.03) and a higher number of local recurrences ( P = 0.05) compared with patients with regional lymph nodes as the site of first metastasis. The 5- and 10-year overall survival rates were 74% and 41%, respectively. Conclusions Regional lymph node metastasis occurred in a higher percentage of patients with conjunctival malignant melanoma than has been reported previously. Preauricular lymph nodes were most commonly involved. Distant metastasis without prior or concurrent lymph node involvement was not a rare event.

Metastatic breast cancer: clinical course, prognosis and therapy related to the first site of metastasis.

Although metastasis is a frequent event in breast cancer patients, insight into the clinical course, prognosis and therapy with respect to the site of the first metastases has been poor and contradictory in former investigations. Follow-up data from 648 patients with metastatic breast cancer were statistically analyzed. Patients with bone metastases at first relapse had better overall survival (median 71 vs. 48 months; p < 0.001) and survival after first metastases (median 24 vs 12 months; p < 0.001) than patients with visceral metastases at first relapse. Bone was the site of first metastasis in 46%, and 71% of patients with metastatic breast cancer developed bone metastases. The localization of the second metastatic site was of prognostic relevance in patients with first visceral metastases, but not in patients with first bone metastases. The presence of osseous metastases correlated significantly with estrogen and progesterone receptor positivity, tumor grading I/II and S-phase fraction <5%. The better prognosis of patients with bone metastases is not determined exclusively by hormone receptor status. The disease is significantly more stable in patients with first bone metastases than in those with first visceral metastases.

Gastric lymphography and detection of sentinel nodes.

The lymphatic drainage system of the stomach was studied using lymphography with various dyes, and several major routes have been shown. Gastric lymph channels are multidirectional and form complex networks. We conducted a retrospective study to know the first site of metastasis from small gastric cancers by examining 89 cases with only one lymph node metastasis. The perigastric nodal area close to the primary tumor was the first site of metastasis in only 62% of the cases. N2 metastasis without N1 involvement was seen in 13%. In order to identify sentinel nodes for local resection of gastric cancer, a novel method needs to be developed.

Resection of metastatic renal cell carcinoma.

Resection of solitary metastases from renal cell carcinoma (RCC) is associated with a 5-year survival rate of 35% to 50%. Selection criteria are not well defined. We retrospectively analyzed our experience with 278 patients with recurrent RCC from 1980 to 1993. One hundred forty-one of 278 patients underwent a curative metastectomy for their first recurrence (44% 5-year overall survival [OS] rate), 70 patients underwent noncurative surgery (14% 5-year OS rate), and 67 patients were treated nonsurgically (11% 5-year OS rate). Favorable features for survival were a disease-free interval (DFI) greater than 12 months versus 12 months or less (55% v 9% 5-year OS rate; P < .0001), solitary versus multiple sites of metastases (54% v 29% 5-year OS rate; P < .001), and age younger than 60 years (49% v 35% 5-year OS rate; P < .05). Among 94 patients with a solitary metastasis, lung (n = 50; 54% 5-year OS rate) was more favorable than brain (n = 11; 18% 5-year OS rate; P < .05). Survival rates after curative resection of second and third metastases were not different compared with initial metastectomy (46% and 44%, respectively, v 43% 5-year OS rates; P = nonsignificant). Favorable predictors of survival by multivariate analysis included a single site of first recurrence, curative resection of first metastasis, a long DFI, a solitary site of first metastasis, and a metachronous presentation with recurrence. Selected patients with recurrent RCC who can undergo a curative resection of their disease have a good opportunity for long-term survival, particularly those with a single site of recurrence and/or a long DFI.

Metastatic rhabdomyosarcoma presenting as intracranial hemorrhage: imaging findings

The CNS is rarely the first site of metastasis for rhabdomyosarcoma. CNS involvement is uncommon, and usually seen as leptomeningeal spread after development of pulmonary metastases. We present the imaging findings in a 13-year-old boy in whom a large intracranial hemorrhage was the initial presentation of surgically documented metastatic prostatic rhabdomyosarcoma. Multiple chest CTs and radionuclide bone scans had previously shown no evidence of pulmonary or osseous metastases. The significance of this case in relation to the possible role of the need for use of chemotherapeutic agents that cross the blood-brain barriers to prevent brain metastasis is discussed.

Frequent incidence of extrapulmonary sites of initial metastasis in patients with liposarcoma.

The vast majority of soft tissue sarcomas spread initially to the lungs and then to other sites. The lung has been the most carefully monitored organ system during routine surveillance for a metastasis. Liposarcoma is one of the most common soft tissue sarcomas and has been noted to have extrapulmonary sites of initial metastasis. This study was undertaken to investigate both the frequency and distinguishing features of initial extrapulmonary metastasis in patients with liposarcoma. A review of 60 patients with liposarcoma treated at the Massachusetts General Hospital (MGH) from 1971 to 1990 was performed. Survival and regression analyses were used to analyze disease free intervals and prognostic factors. Metastatic disease occurred in 37% of patients and local failure in 17%. Among the subset of patients who underwent primary definitive surgery at the MGH, the incidence of local failure was 3%. An unusually high incidence of extrapulmonary site of first metastasis was found. Isolated extrapulmonary disease was the site of initial metastasis in 59% of patients. In contrast to patients with an initial pulmonary metastasis, patients with an initial extrapulmonary metastasis had a statistically significant (P = 0.001) longer disease free interval from diagnosis to first metastasis. Liposarcoma, in comparison with other soft tissue sarcomas, has a different pattern of metastatic spread, with a tendency toward extrapulmonary sites. In addition, patients with extrapulmonary metastases have a longer disease free interval compared with patients with pulmonary metastasis.

Human melanoma cells derived from lymphatic metastases use integrin alpha v beta 3 to adhere to lymph node vitronectin.

Human melanoma is a highly metastatic cancer and the regional lymph nodes are generally the first site of metastasis. Adhesion to cryostat sections of human lymph nodes was therefore studied using two human melanoma models established from lymph node metastases, namely, MeWo cell lines of diverse metastatic potentials and a highly metastatic cell line of recent origin designated MIM/8. We found a good correlation between the metastatic potentials of the melanoma cells as measured in nude mice and their ability to adhere to cryostat sections of human lymph nodes. When adhesion to immobilized extracellular matrix proteins was measured, a significant increase in adhesion, which correlated with increased metastasis, was seen mainly on vitronectin and to a lesser extent on fibronectin. The adhesion to vitronectin and to the frozen sections were specifically blocked by an RGD-containing peptide, mAb 661 to vitronectin and mAb LM609 to integrin alpha v beta 3. FACS analysis revealed a significant and specific increase in cell surface expression of alpha v beta 3 on the metastatic cells as compared to the parent line. Together these results suggest that the adhesion of melanoma cells to lymph node vitronectin via the alpha v beta 3 receptor plays a role in the process of lymphatic dissemination.

C-erbB-2 positive breast tumours behave more aggressively in the first years after diagnosis.

In a retrospective study the expression of the c-erbB-2 oncogene was determined immunohistochemically in 276 breast cancer samples from 253 patients with the antibody 21N. The follow-up period was between 7 and 12 years. This study showed a trend for an inverse relationship between c-erbB-2 positive tumours and estrogen receptors (ER). A correlation was assessed between c-erbB-2 positive tumours and histological grade, liver metastases as first site of metastases, disease free survival time (DFS) in the second and third year after diagnosis and overall survival time (OST) in the third and fourth year after diagnosis. A trend was seen between c-erbB-2 positive tumours and tumour size. No correlation was found between c-erbB-2 positive tumours and age at diagnosis. The method of operation and lymph node involvement. From this study we conclude that there is a significant difference in prognosis the first years after diagnosis, but this difference seems to vanish in a longer follow-up period of 12 years. This provides us with an explanation for the discrepancies in literature concerning c-erbB-2 expression and prognosis in breast cancer. Some investigators did not show differences in prognosis between positive and negative cases after a long follow-up period whereas investigations with a short term follow-up period up to 2-3 years have indeed established a more aggressive behaviour of c-erbB-2 overexpressionary tumours.

ANATOMY AND BIOPSY OF SENTINEL LYMPH NODES

Lymphangiograms performed via the dorsal lymphatics of the penis demonstrate drainage into a specific lymph node center, the so-called sentinel lymph node, which is located close to the superficial epigastric vein between the latter and the superficial external pudendal vein. Anatomically, clinically, and pathologically, the sentinel lymph node is the first site of metastasis and often is the only lymph node involved. We recommend preliminary bilateral sentinel lymph node biopsy, with inguinofemoral dissection being performed only when this node is involved. If the biopsies are negative for metastases, no further surgical therapy is immediately indicated, and the patient needs to be observed closely with monthly examination for 1 year and examination every 2 months for 3 years. The clinical staging of cancer of the penis needs a new review for further evaluation of different modalities of treatment. Sentinel lymph node biopsy must not be used to determine whether node dissection is needed in patients with evident clinically positive nodes. Also, the concept of sentinel lymph node should not be applied in the management of patients who will not be available for frequent follow-up. If during physical examination, suspect lymph nodes are found other than the classic sentinel node, these lymph nodes must be removed for staging and subsequent treatment planned according to the histologic report.

Prognosis of Resected Well-differentiated Neuroendocrine Carcinoma of the Lung

Among lung tumors, well-differentiated neuroendocrine carcinomas are often misdiagnosed or may go unrecognized. Nineteen cases of well-differentiated neuroendocrine carcinoma (WDNC) were assessed at the National Cancer Institute of Milan over a ten-year period. There was only one woman and the age range was 50 to 77 years. Most of the patients were smokers (83 percent). All tumors were radically resected. There were 12 lobectomies, two sleeve-lobectomies, three bilobectomies, one pneumonectomy, and two segmentectomies (one patient had two synchronous WDNCs). There was neither operative mortality nor major complications. Sixteen tumors were stage 1, three were stage II, and one was stage IIIa. Five patients had adjuvant chemotherapy (cyclophosphamide, doxorubicin, and vincristine [CAV] regimen). One patient was given local or regional radiotherapy. In ten patients the tumors recurred, even though four had had adjuvant treatment. The brain was the first site of metastasis in seven cases. The pathologic stage seemed not to be closely related to the appearance of metastases (six patients with stage I disease had recurrences). Only two patients with recurrence were still alive 12 and 103 months after the procedure. The percentage of survival for patients with stage I disease after more than 100 months was 68 percent. WDNC is similar to small-cell lung carcinoma (SCLC) with regard to the neurotropism of metastases. Surgery is curative for more than one half of the patients with localized disease. Therefore, multimodal therapy, probably based on tumor behavior and investigations of tumor markers, is advisable.

Steroid hormone receptor activity of primary human breast cancer and pattern of first metastasis

A series of 258 breast cancer patients with known estrogen receptor (ER) status of the primary tumour who subsequently developed metastases were reviewed for site of first metastasis. In 188 cases progesterone receptor (PgR) data were also available. Univariate analysis showed metastatic patterns to differ statistically significantly related to ER status and (less pronounced) PgR status of the primary tumour. Patients with ER-positive tumours had bone metastases three times more often than patients with ER-negative tumours. With respect to PgR-positive and PgR-negative tumours this frequency differed by a factor of two. With regard to visceral metastases ER and PgR status were equally potent prognosticators, patients with receptor negative tumours having a 50% higher frequency of visceral metastasis than patients with receptor positive tumours. Assessment of metastatic patterns in relation to combined receptor status did not substantially enhance the discriminatory value of ER and PgR when assessed separately. Multivariate analysis showed that the observed differences in metastatic patterns were all attributable to differences in the ER status of the primary tumour, and were not influenced by age, menopausal status, axillary lymph node involvement, duration of disease-free interval (DFI), mode of postoperative treatment, or the PgR status of the primary tumour.

Angiosarcoma of the breast with report of unusual site of first metastasis

Angiosarcoma of the breast accounts for less than 1% of all primary breast lesions. It occurs at all ages, but more frequently in younger women than does primary breast carcinoma. It often has a rapidly progressive clinical course and, as in one of the reported cases, can present with unusual sites of metastases even after a long disease-free interval.

Resection of pulmonary and hepatic metastasis in the management of cancer

Metastasis from cancer was first reported by a French surgeon, Ledran, in 1720.’ Specific mechanisms were not postulated for another century, until Virchow delineated the cellular basis of cancer.* It soon became evident that lung and liver were the two most common sites of metastases in patients dying of malignancy. Although the natural history of most solid tumors as observed in the nineteenth and early twentieth centuries led to therapeutic approaches such as wide primary tumor and regional resection, more precise understanding of the biology of primary tumor development and metastasis has more recently justified novel adjuvant regional and systemic therapeutic approaches. However, despite the curability of many nonsolid and a few solid cancers by biologic response modifier or chemotherapy, the role of systemic treatment in advanced adult solid tumors has been disappointing. During the last two decades, numerous investigators have observed that a small proportion of patients with recurrent solid tumors present with limited regional involvement.3*4 In some of these biologically select patients with limited regional recurrence, surgical resection may be potentiaIIy curative. Among all cases of fatal malignancy, pulmonary metastasis occurs in 30%, and one-half to two-thirds of these patients have metastases that appear clinically to be confined to the 1ungs.4*5 Approximately one-half of these patients (only 5 to 10% of the total group) may be eligible for pulmonary metastasis resection with curative intent.5 The biology of pulmonary metastasis is dependent upon primary tumor histology. For instance, the pulmonary parenchyma may be the first site of metastasis in 90% of patients with disseminated sarcoma.6 In patients who recur or are first diagnosed with disseminated gastrointestinal primaries, 50% will have liver only or liver as the first site of recurrence.’ The incidence of liver metastasis at the time of primary cancer treatment varies from 20% with gastric cancer, to 25% with colorectal cancer, and up to 49% of patients with pancreatic cancer.’ Only in patients with limited liver metastases from colorectal carcinoma is regional disease not an immediate precursor of disseminated systemic recurrence. Although 60 to 70% of all patients who die of colorectal cancer have liver metastases,’ only 10 to 20% will fail only or first in the liver, and only 5 to 10% of these will be amenable to potentially curative surgical resection.9 Thus, patients with pulmonary or hepatic metastases that are resectable represent an extremely highly selected biologic subset among the overall group of patients with recurrent solid tumors. The analysis of results of pulmonary and hepatic metastasectomy must take this selection bias into account.4A In this article, we attempt to summarize the biologic rationale and the technical considerations of metastasectomy, to analyze patterns of failure after metastasectomy, and to look ahead to future therapeutic strategies based on analysis of failure. Although a variety of malignant tumors including both carcinomas and sarcomas metastatic to the lung may be cured by pulmonary resection, curative resection or metastatic tumors to the liver is limited to metastases from colorectal cancer. Anecdotal successes only have been reported after resection of isolated hepatic metastasis from renal cell cancer, various gynecologic cancers, melanoma, and sarcoma.3