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Surgical Remissions Extend Survival
written and compiled by doctordee
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Metastasectomies, the surgical removal of metastases, and/or the surgical removal of local recurrence, prolong survival time. The complete removal of all known tumor, rendering a patient NED [No Evidence of Disease], is also called a surgical remission.
So, if you have a local recurrence or a metastasis, it would be best to have it or them removed, if possible. This is so important for survival benefit, that if the tumors are called inoperable by a local surgeon, you can and should seek expert opinion elsewhere. What is one surgeon's "inoperable" is another surgeon's daily work.

VATS, video assisted thoracoscopic surgery, or chest keyhole surgery, is a possible substitution for the more arduous thoracotomy, if the tumors are accessible and 3cm or less in size. RFA, or radiofrequency ablation, is sometimes used to ablate [in this case, cook] metastases in lung, liver, and various other organs. If the tumors are inoperable, sometimes RFA can ablate them.

There is Rusch's review article on "Pulmonary metastasectomy. Current indications"
Her conclusions are: "Complete surgical resection is critical to achieving long-term survival... The decision to proceed with the surgical resection of pulmonary metastases should be a multidisciplinary one, made jointly by the thoracic surgeon and the medical oncologist."
Fetch Abstract

Then there is the The European Organization for Research and Treatment of Cancer [EORTC] study on treatment of soft tissue sarcoma lung metastasectomies. They concluded that "Surgical excision of lung metastases from soft tissue sarcomas is well accepted and should be considered as a first line of treatment if preoperative evaluation indicates that complete clearance of the metastases is possible. Further investigation is needed before chemotherapy can be recommended as additional therapy."
Fetch PMID: 8616759

"Prognostic grouping that takes into account number of metastases, disease-free interval and resectability correlates significantly with expected survival regardless of histological typing of the primary tumor."
Fetch PMID: 11149200

CancerNet from the National Cancer Institute, has PDQ Information for Health Care Professionals about Surgical Removal of Lung Metastases .

Three more articles to bring to your attention:

Metastasectomy for limited metastases from soft tissue sarcoma.
Abdalla EK, Pisters PW. Department of Surgical Oncology, MDA, Houston

"The development of metastatic soft tissue sarcoma ... is associated with a poor prognosis. Surgical resection of isolated solitary or multiple metastases is the only curative treatment; all other forms of treatment are considered palliative. ... Over the past decade, nonresectional ablative approaches have been developed to manage visceral metastatic disease. These ablative procedures include cryosurgery, radiofrequency tumor ablation, and alcohol injection. All such procedures are considered investigational; outcome should be compared to that achievable with traditional surgical metastasectomy. The optimal sequence of treatments and role for perioperative (combined with metastasectomy) chemotherapy are unknown. Given the potential curative nature of metastasectomy, all patients with metastatic soft tissue sarcoma should be evaluated for the possibility of surgical resection. Patients with good performance status who have radiographically resectable disease should be considered for metastasectomy."
Fetch PMID: 12392639

Long-term results of surgical resection of lung metastases.
Hendriks JM, Romijn S, et al
Antwerp University Hospital, Edegem, Belgium.

"Between 1990 and 2000, 56 consecutive patients underwent lung resection for removal of metastatic disease. Mortality, disease-free interval, and overall survival were studied. ...Multivariate analysis showed that survival for patients who underwent 2 or more metastasectomies was surprisingly good with a 5-year survival rate of 46%. Survival was not related to disease-free interval, multiple lung metastases, or pneumonectomy. It is in accordance with some reports that a short disease-free interval, numerous lung metastases, or recurrence after the first metastasectomy should not preclude patients from operation."
Fetch PMID: 11868501

Long-term results after repeated surgical removal of pulmonary metastases.
Kandioler D, Kromer E, et al
University of Vienna Medical School, Austria.

"Although surgical resection is accepted widely as first-line therapy for pulmonary metastases, few data exist on the surgical treatment of recurrent pulmonary metastatic disease. In a retrospective study, we analyzed patients who were operated on repeatedly for recurrent metastatic disease of the lung with curative intent over a 20-year period. ...
From 1973 to 1993, 396 metastasectomies were performed in 330 patients. ...The 5- and 10-year survival rates after the first metastasectomy were 48% and 28%, respectively. The overall median survival was 60 months. A mean disease-free interval (calculated for all intervals, with a minimum of two) of greater than 1 year was significantly associated with a survival advantage beyond the last operation. Univariate analysis failed to show size, number, increase or decrease in number or size, or distribution of metastases as factors related significantly to survival. ...We conclude that patients who are persistently free of disease at the primary location but who have recurrent, resectable metastatic disease of the lung are likely to benefit from operation a second, third, or even fourth time."
Fetch PMID: 9564899
Medical Journal Corroboration
Below are some searches and more articles documenting the increased survival time with judicious use of surgical excision of tumor.

Supporting data can be found on these Pubmed Searches:

Pubmed search on Metastasectomies AND Sarcoma

Pubmed search on Metastasectomy AND Sarcoma

The first search has 11 articles, and is mostly concern with lung metastases. The second search has even more articles, and discusses metastasectomies of other organs as well. To understand how to use Pubmed, go to Access to Medical Information .
Further Corroboration
Additional References:

1. Improved survival following pulmonary metastasectomy in soft tissue sarcoma (STS): Comparison of cohorts treated with and without resection
Year: 2003 ASCO Abstract No: 3304
Author(s): I.R. Judson, et. al. Royal Marsden and Royal Brompton Hospitals, London UK

...Data collected prospectively of pts treated with pulmonary metastasectomy for STS were compared to pts with lung metastases as a sole metastatic site managed without resection.

...From 1991-2001 89 pts underwent complete resection of lung metastases and 78 similarly fit pts with lung as a sole metastatic site were managed without resection.

... Survival was superior in the resection group (medians 23 v 13 months; p<0.001). ... Following metastasectomy 45 pts relapsed with lung metastases alone, 21 with metastases at other sites, and 23 have not relapsed. The only factor predicting for second lung relpase was grade ... but grade did not predict for relapse at other sites. The number of metastases resected, 1 or >1, was not prognostic... 17 (19.1%) pts have undergone further metastasectomies. 11 (12.4%) pts have survived for at least 5 years after resection.

Conclusion: Pts managed by pulmonary metastasectomy for STS had superior survival compared to pts managed without resection. This could not be entirely explained by the fact that these pts were younger and had a longer DFI. In this group the number of metastases resected does not predict survival. These data support screening pts for operable pulmonary metastases following treatment of a primary STS.
Fetch Abstract

2. Lancet Oncology, Volume 1, Number 2, 01 October 2000
Management of soft-tissue sarcomas: an overview and update

Samuel Singer, George D Demetri, Elizabeth H Baldini, and Christopher DM Fletcher
Brigham and Women's Hospital, Boston MA, Dana-Farber Cancer Institute, Boston MA
"Although detailed discussion is beyond the scope of this review, it
should be mentioned that there is also a clear role for pulmonary
metastasectomy in sarcoma patients with metastatic disease.[10] In
cases with relatively few (up to 3) metastatic tumour nodules and a
longer tumour doubling time, such surgery may be associated with
significant prolongation of survival."

3. Pulmonary metastases from soft tissue sarcoma: analysis of patterns of diseases and postmetastasis survival.
Billingsley KG, Burt ME, Jara E, Ginsberg RJ, Woodruff JM, Leung DH, Brennan MF.
Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.

"For patients with soft tissue sarcoma, the lungs are the most common site of metastatic disease. ... To date, resection of disease has been the only effective therapy for metastatic sarcoma."
"Resection of metastatic disease is the single most important factor that determines outcome in these patients. Long-term survival is possible in selected patients, particularly when recurrent pulmonary disease is resected. Surgical excision should remain the treatment of choice for metastases of soft tissue sarcoma to the lung."
Fetch PMID: 10235518

4. Soft-tissue Sarcomas
Peter W. T. Pisters,MD, Ephraim S. Casper,MD, Brian O'Sullivan,MD, and Edward M. Soffen,MD


"The most common site of metastatic disease involvement of soft-tissue sarcoma is the lung. Rates of 3-year survival following thoracotomy for pulmonary metastasectomy range from 23% to 42%. This fact, combined with the limited efficacy of systemic therapy, is the basis for the recommendation that patients with limited pulmonary metastases and no extrapulmonary disease should undergo thoracotomy and metastasectomy."

"Appropriate patient selection for this aggressive therapeutic approach to metastatic disease is essential. The following are generally agreed upon criteria: (1) the primary tumor is controlled or controllable; (2) there is no extrathoracic metastatic disease; (3) the patient is a medical candidate for a thoracotomy; and (4) complete resection of all disease appears to be possible."

"Preresection chemotherapy Chemotherapy is often recommended before resection of lung metastases. However, there are no convincing data to support this approach."

from the CancerSource site.

5. ERS research seminars- Isolated Lung Perfusion
Edegem (Antwerp) Belgium
April 27-28, 2002

G. Friedel
Gerlingen, Germany

Long-term survival in patients with lung metastases, prognostic factors

However, the curative potential of metastasectomy had been recognized slowly. Pulmonary metastasectomy has been gradually accepted as a surgical procedure of proved therapeutic value in selected cases. Several years after the first resection of a single lung metastasis, discovered during the excision of a chest wall sarcoma, elective surgery has been occasionally offered to selected patients with single pulmonary metastases or a long disease-free interval (DFI). In only a few selected centers has metastasectomy been applied systematically to multiple or bilateral lesions, with the hope of improving long-term survival. In addition, adjuvant chemotherapy has also been used to facilitate surgical resection.

Although the criteria of eligibility have been progressively expanded, it is difficult to assess the real proportion of patients with isolated lung metastases who are candidates for salvage surgery, because the denominator cannot be properly defined in most clinical conditions. In some tumors, such as sarcomas, germ cell tumors, or pediatric malignant tumors, a high proportion (>50%) of all patients with lung metastases may be candidates for metastasectomy. ...

For all these reasons it appeared reasonable to try to overcome the limits of present knowledge by a cooperative multicentric clinical study. The International Registry of Lung Metastases was launched in 1990 with a few clear objectives: set up a common database through the major centers of thoracic surgery in Europe and the United States to facilitate the exchange of information; perform a more homogeneous evaluation of the results for the various primary tumors; define prognostic factors by multivariate analysis; propose a novel system of stage grouping; and define areas of uncertainty concerning surgery and other therapeutic modalities to be explored by prospective randomized trials.

A new comprehensive database was designed at the Istituto Nazionale Tumori of Milan to provide a simple and flexible instrument for the Registry. This included a single record form for each patient, divided into four different sections: identification of patients, description of the primary neoplasm (time, site, histology, type of therapy), description of every metastasectomy performed (date, number and size of deposits, type of operation, and combined therapies), and the updated follow-up (pulmonary recurrence, relapse in other organs, treatment, and outcome). All data (except identification of patients) were precoded; in addition, extended description was requested for the primary site, histologic type, and concurrent nonpulmonary resections. Patients who underwent planned sequential or staged thoracotomies were considered to have had one single metastasectomy and not redo surgery. All major centers of thoracic surgery with a specific experience in the surgical management of lung metastases were contacted and offered the opportunity to join the Registry. From 1991 to 1995, 5290 patients were enrolled in the International Database, covering a period of more than four decades. In fact, the first metastasectomy was performed in 1945. Adequate information was available for the vast majority of these patients.

All patients who underwent resection of lung metastases (metastasectomy) with curative intent were considered eligible for the Registry. Incomplete ablation of pulmonary metastases, although not necessarily a reason for exclusion, had to be unequivocally identified. Eradication of the primary tumor and absence or effective treatment of metastases in other organs, before or concurrent with pulmonary metastasectomy, were considered mandatory for inclusion in the Registry. The following variables were tested: sex, age, number of resected as well as pathologically proved metastases, DFI, and histologic type and site of the primary tumor. For the multivariate analysis, primary histology codes were grouped as follows: breast, lung, bowel, kidney, uterus, and head and neck cancer, osteosarcoma, other bone sarcomas, histiocytoma, leiomyosarcoma, synovial sarcoma, other soft tissue sarcomas, Wilms' tumor, teratoma, embryonal carcinoma, other germ cell tumors, and any other tumors.

In 42% of patients lung metastases were from sarcomas ... In the whole series, 31% of patients had a DFI of 0 to 11 months, including 11% who had synchronous metastases; 36% had a DFI of 12 to 35 months and 31% of 36 months or more. Median DFI was 19 months. In most patients (64%) with germ cell tumors the DFI was less than 12 months; the corresponding value was 39% for sarcomas, 21% for epithelial tumors, and 17% for melanomas. In 126 (2%) patients the DFI was not specified.

The surgical approach was monolateral thoracotomy in 58% of patients, bilateral synchronous or staged thoracotomy in 11%, median sternotomy in 27%, and thoracoscopy in only 2%. For the large majority of patients the maximum resection volume was sublobar, including 67% wedge resections, 9% segmentectomies, 21% lobectomies or bilobectomies, and 3% pneumonectomies. Two hundred three lobectomies and six pneumonectomies were performed through median sternotomies. Surgical resection included other sites, such as chest wall, diaphragm, pleura, lymph nodes, mediastinal organs, or liver in 9% of patients.

On the basis of pathologic assessment, single metastases accounted for 46% and multiple metastases 52%. Overall, 26% had four or more metastases, 9% (n = 457) ten or more, and 3% (n = 165) twenty or more; the maximum number of lesions resected was 154. Multiple metastases were resected in 64% of sarcomas, 57% of germ cell tumors, 43% of epithelial tumors, and 39% of melanomas.

Metastases to hilar or mediastinal nodes were found in 5% of cases, corresponding to 11% of germ cell tumors, 8% of melanomas, 6% of epithelial metastases, and only 2% of sarcomas.

Chemotherapy was administered at the time of occurrence of lung metastases in 38% of patients; in 22% before metastasectomy and in the remaining 16% only after lung resection. The proportion of patients receiving chemotherapy was slightly higher (56%) in the group having incomplete resections and in patients with multiple metastases (45% vs 29% with single metastases). One fifth of patients underwent multiple metastasectomies (redo surgery): 15% had two metastasectomies, 4% (183) three operations, and 1% (73) four or more; the maximum number of metastasectomies performed on a single patient was seven. Within the subset of 2988 patients who had both preoperative radiologic and postoperative pathologic assessment of the number of lesions with complete metastasectomy, it was possible to estimate the accuracy of clinical staging. Overall, the radiologic assessment of the number of lung metastases was accurate in 61% (n = 1812) of patients, underestimated in 25% (n = 746), and overestimated in 14%. In the group of 1854 patients who underwent monolateral thoracotomy, the radiologic accuracy was 75%, underestimation 16% and overestimation in only 8%. However, in the group of 1134 patients who had median sternotomy or bilateral thoracotomy, the number of radiologic metastases was accurate in only 37%, underestimated in 39% and overestimated in 25%. These data underline the importance of bilateral surgical staging in lung metastasectomy.

The total number of perioperative deaths was 51, corresponding to an overall operative mortality of 1.0%.

The survival after complete metastasectomy was 36% at 5 years, 26% at 10 years, and 22% at 15 years, with a median survival of 35 months; the number of patients alive at these intervals was 809, 254, and 78, respectively. The corresponding survivals for incomplete resections were 13% at 5 years and 7% at 10 and 15 years, with a median of 15 months. In this group 35 patients were alive at 5 years, five at 10 years, and only one at 15 years. The difference was highly significant.

For patients with a DFI of 0 to 11 months, the survival was 33% at 5 years and 27% at 10 years, with a median of 29 months. For a DFI of 12 to 35 months, the corresponding values were 31%, 22%, and 30 months; for a DFI of 36 months or longer, survivals were 45%, 29%, and 49 months, respectively.

Patients with single metastases had a survival of 43% at 5 years and 31% at 10 years, with a median of 43 months. In the group of patients with two or three metastases, the survival was 34% at 5 years and 24% at 10 years, with a median of 31 months. Patients with four or more metastases had a lower survival: 27% at 5 years and 19% at 10 years, with a median of 27 months. However, even in the group of patients who had 10 or more metastases resected (n = 342), the survival reached 26% at 5 years and 17% at 10 years, with a median of 26 months.

Patients with germ cell tumors had by far the best survival (68% at 5 years and 63% at 10 years) and melanoma the worst (21% at 5 years and 14% at 10 years, median 19 months). The survivals of patients with epithelial tumors (37% at 5 years and 21% at 10 years, median 40 months) and sarcomas (31% at 5 years and 26% at 10 years, median 29 months) did not differ significantly when these two large groups were compared.

However, there were significant differences among the specific histologic types of sarcoma and the various sites of epithelial cancer (discussed later). The survival of all tumor types combined (other than germ cell and Wilms' tumors) was 34% at 5 years and 23% at 10 years, with a median of 33 months (not shown). Median time to recurrence was 10 months. The probability of relapse was higher for sarcomas and melanoma (64%) than for epithelial (46%) or germ cell (26%) tumors. However, the site of relapse was significantly different among the four types. In sarcomas, intrathoracic relapse accounted for 66% of all recurrences, whereas in melanoma 73% of relapses involved extrathoracic organs. Epithelial and germ cell tumors showed an intermediate pattern. Median time to recurrence was shorter in sarcomas than in epithelial tumors (8 vs 12 months).

In accordance with the relapse pattern, the proportion of patients who underwent a second metastasectomy was higher in recurrent metastatic sarcomas (53%) than in any other type. Median interval between the first and second metastasectomy ranged between 10 months for sarcomas and 17 months for epithelial tumors. The long-term outcome of patients who were treated by a second metastasectomy was remarkably good: a 44% survival at 5 years and 29% at 10 years, compared with 34% and 25%, respectively, for patients having had one single operation. This is not surprising in the short term, inasmuch as redo surgery is generally offered to patients with limited pulmonary relapse and good general condition. However, the favorable long-term results suggest a real curative benefit of repeated salvage operations, rather than a simple selection effect.

To build a prognostic grouping that would be simple, discriminant, and valid in different tumor types (other than germ cell and Wilms' tumors), we used three parameters of prognostic significance: resectability, DFI, and number of metastases. Among patients with resectable lesions, a DFI of less than 36 months and multiple metastases were seen to be independent risk factors. Four clearly distinct prognostic groups could thus be identified:

* Group I: Resectable, no risk factors (DFI > 36 months, and single metastasis)
* Group II: Resectable, one risk factor (DFI < 36 months or multiple metastases)
* Group III: Resectable, two risk factors (DFI < 36 months and multiple metastases)
* Group IV: Unresectable The difference among the curves was massively significant.

Median survival was 61 months for group I, 34 months for group II, 24 months for group III, and 14 months for group IV. The discriminant power of this prognostic grouping was tested on different primary tumors and proved to be highly significant in each specific tumor type.

The results of this International Registry of Lung Metastases confirm that metastasectomy is a potentially curative treatment that can be administered safely with low mortality. In keeping with general principles of surgical oncology, complete removal of all metastatic deposits is associated with long-term survival. Our data suggest that radiologic staging is inaccurate in a large proportion of cases and that intraoperative exploration by an experienced surgeon is required to optimize resection of all metastases. Thorough intraoperative staging is therefore required to identify and resect all metastases. In this respect, video-assisted thoracoscopy cannot provide optimal intraoperative identification of pulmonary metastases, particularly when more than one lesion is identified in the preoperative period. Our results also suggest that multiple metastasectomies may be required to achieve permanent cure, and that repeated salvage surgery can be safe and effective over the long term.

Patient with lung metastases of breast cancer are rarely undergo surgical resection because medical and gynecological oncologists still regard metastatic breast carcinoma as an incurable disease. Based on the assumption that it is a systemic disease, local surgical measures are rejected or only considered as palliative procedures in symptomatic metastases. However, in another part of this study with the so far largest documented number of resected lung metastases from breast cancer it is shown that metastasectomy at present provides better long-term results than chemotherapy and hormone therapy. Whether high-dose chemotherapy with stem cell support is able to achieve comparable survival data has to be clarified by future studies. This applies also to the new therapeutic options like immuntherapy with HER2 monclonal antibodies or the new hormon agents. At least in risk group I as defined by the International Registry of Lung Metastases, metastatic surgery at present has to be regarded as the therapeutic option with the longest survival rates thus to be offered to the patients as the most effective therapeutic procedure. In our opinion, with 15-year survival rates of 26%, the statement that a curative approach is not possible in lung metastases from breast cancer, is not tenable.

last updated January 2004

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