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    BE A PARTNER . . . NOT A PATIENT

    The primary mission of the Texas Cancer Center is to show you the great body of medical evidence which supports conservative (limited) surgery for patients with cancer. Patients and doctors alike have a natural desire to eliminate every last cancer cell - "Get It ALL." Medical research tells us that the entire tumor should be removed. But, the surgeon does not need to perform radical surgery to eradicate nearby microscopic cells which might be cancerous. This treatment strategy has been proven to be successful for breast cancer, melanoma, the soft tissue sarcomas, and other cancers.

    For patients with soft tissue sarcomas, many surgeons perform a very wide excision, leaving a large defect, and then give postoperative radiation therapy. But limited surgery, which removes only the tumor and a margin of normal tissue, cures just as many patients. Radiation therapy reduces the chance that the tumor may recur locally, but it does not improve survival. This has been proven in careful, scientific studies. The Texas Cancer Center encourages conservative surgery without radiation therapy as practiced by P.L. Fabrizio and associates from the Mayo Clinic. Additional medical research supporting our recommendations can be found in our "Medical Research" section. Most of this research is directly linked to the National Library of Medicine. There are no medical studies which successfully refute this conservative treatment strategy.

    INTRODUCTION

    Sarcomas are cancers of the body tissues, as opposed to specific organs. They arise in bone, cartilage, muscle, fat, nerves, blood vessels and other connective tissue. They represent about two percent of all adult cancers. Most sarcomas arise in the extremities. But they can arise within almost any organ in the body.

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    STAGES OF DISEASE

    Like other cancers, stage is determined by both tumor size and the extent of tumor spread. But among soft tissue sarcomas tumor grade plays an very important role in determining prognosis. Prognosis is also influenced by the location of the tumor. A superficially located tumor has a better prognosis that one which is deep inside an extremity or other part of the body. There are several systems, including the complex TNM system. The most commonly used system in the United States has been approved by the American Joint Committee on Cancer (AJCC). It is based upon the tumor grade and size.

    Stage IA - Grade 1 that is localized and smaller than 5 cm.

    Stage IB - Grade 1 that is localized and larger than 5 cm. The five-year survival rate for stage I tumors is 70% 85%.

    Stage IIA - Grade 2 tumor that is localized and smaller than 5 cm.

    Stage IIB - Grade 2 tumor that is localized and larger than 5 cm. The five-year survival rate for stage II tumors is 50% 70%.

    Stage IIIA - Grade 3 tumor that is localized and smaller than 5 cm.

    Stage IIIB - Grade 3 tumor that is localized and larger than 5 cm.

    Stage IIIC - Tumor of any grade or size with lymph node spread. The five-year survival rate for stage III tumors is 25% 45%.

    Stage IVA Tumor of any grade, size, or lymph node status, which grossly invades adjacent structures, e.g., major blood vessels or nerves.

    Stage IVB Distant metastases are present. The five-year survival rate for stage IV tumors is about 20%

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    TYPES OF TREATMENT

    Surgery

    Traditional surgery has been amputation or wide excision including a broad margin of apparently normal tissue. When muscles are involved, surgeons have often removed the entire muscle group. If the tumor is near the shoulder or hip, the entire joint has been removed. If the tumor involves a major blood vessel, the vessel has been removed and replaced with an artificial graft. When bone is removed, it can often be replaced with bone graft or metal. Even after radical excision local recurrence rates of 25 30% are common. Recently more surgeons are practicing more conservative surgery, including limb sparing techniques. Some surgeons recommend Mohs' micrographic surgery.

    Radiation Therapy

    Radiation therapy is used to reduce local recurrence especially after surgery that spared the limb from amputation. Doses of 6,000 7,000 cGy given over six to seven weeks are common. Radiation may also be given prior to surgery to reduce the size of a large tumor. Local recurrence rates of 20 25% are common.

    Chemotherapy

    Chemotherapy has been very effective in bone sarcomas, Ewing's sarcomas, and rhabdomyosarcomas. Chemotherapy has been much less effective in other soft tissue sarcomas. Adriamycin is the most commonly used agent for soft tissue sarcomas. Adjuvant chemotherapy is not very effective. Patients with tumors, which are 5 cm or smaller should not be treated with adjuvant chemotherapy. Currently it is recommended that patients with large tumors or distant metastases receive treatment as participants in a clinical trial. Preoperative (neoadjuvant) chemotherapy can be used to shrink large tumors prior to surgery.

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    TCC ANALYSIS

    Limb sparing operations are gaining acceptance and are available at most large medical centers. As with breast cancer, local recurrence following radical surgery, e.g., amputation, is a worrisome event, and is associated with a decreased survival. Local recurrence following conservative surgery (local persistence) has a much better prognosis. This observation has been confirmed by several medical centers in Europe, Japan and the United States. Therefore, surgeons can prudently perform one of the conservative operations discussed above without compromising the patient's survival. As with breast cancer the next area of debate will be the need for routine postoperative radiation therapy. I have found no study which demonstrates that postoperative radiation improves the survival of patients with this disease.

    The suggestion that local recurrence has little affect on survival would have been heresy just a few years ago. But today wide local excision and radiation therapy are gaining acceptance in the treatment of soft tissue sarcoma. The central question is,"What is the clinical significance of local recurrence?" Specifically, does recurrent disease cause distant metastasis or is it merely a sign of aggressive disease? If local recurrence jeopardizes patient survival, then aggressive local control measures are indicated. Current evidence overwhelmingly suggests that local recurrence is merely a sign. It can be a sign that the tumor has already spread. It can also be a sign that the tumor is very aggressive. But if local recurrence is treated promptly, there is no reliable evidence that it causes the tumor spread.

    As with breast cancer, I do not believe that radiation therapy is routinely needed. If local control has an independent effect to enhance survival, we should see this benefit among patients treated with radiation therapy. Unfortunately, this relationship does not occur. Most authorities report that radiation therapy improves local control, but does not affect survival. The single one exception to this observation is discussed in the appendix.

    These observations support the present trend toward limb preservation and should encourage surgeons and radiation therapists to strive toward an even greater concern for the functional and cosmetic results of their therapy. By reading the section of the appendix devoted to soft tissue sarcomas, you should gain confidence in conservative treatment.

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    TREATMENT OPTIONS

    Stage I - Localized grade 1 tumors.

    Surgical excision of all gross and microscopic disease. If possible a wide margin (2 cm) of normal tissue should also be excised. If needed to preserve important structures, the margin may only be pathologically negative. Removal of muscle groups and wide margins (greater than 2 cm) of normal tissue is not necessary. Radiation therapy is not routinely necessary. It may be used if the tumor was excised with a narrow margin close to a vital structure such as an artery or nerve.

    Stage II - Localized grade 2 tumors

    Same as stage I. Preoperative (neoadjuvant) chemotherapy or radiation therapy may be used to shrink a tumor. Postoperative radiation therapy may be used more often than in stage I patients.

    Stage III - Localized grade 3 tumors.

    Same as stage I. Preoperative (neoadjuvant) chemotherapy or radiation therapy may be used to shrink a tumor. Postoperative radiation therapy may be used more often than in stage II patients. Patients with stage IIIC disease should have their positive lymph nodes excised.

    Stage IVA - Patients with treated with preoperative chemotherapy and/or radiation therapy.

    Stage IVB - The primary tumor can be treated as described above. If the patient has one or a few metastases to the lungs these may be excised. Cure is possible in about 30% of such patients. Patients with diffuse disease may wish to consider chemotherapy. But, results thus far are not encouraging.

    Special Considerations

    Recurrent tumors Most authorities recommend more aggressive treatment if a tumor recurs locally. In 1968, Keyhani and colleagues reviewed the experience with of Memorial SloanKettering Hospital with 204 patients with rhabdomyosarcoma treated from 1932 to 1962. Eighty-five patients had their primary surgery performed at Memorial, and 75 patients presented initially with recurrent disease following initial surgery elsewhere. The fiveyear survival calculated from the time of first treatment at Memorial was 37% among primary cases and 38% among recurrent cases. Measured from the time of first treatment, survival among the group with recurrent disease would have been longer. Ariel and colleagues reported similar statistics involving the same tumor from Memorial in 1975. They concluded that their results ". . . should help dismiss the pessimism which prevails once a recurrence is noted subsequent to major therapy." Ariel was one of the first to question the grave prognosis of local recurrence. I believe that recurrent tumors may be treated as described above. The patient should be reassured that promptly treated local recurrence does not reduce survival. Aggressive treatment is suitable in the patient who is anxious about the possibility of future recurrences.

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    MEDICAL RESEARCH

     Many soft tissue sarcomas are surrounded by a thick capsule. In the early part of this century some surgeons would simply extract the tumor out of the capsule. Since tumor cells were present in the capsule, this operation resulted in a high rate of local recurrence. In 1936 Warren and Sommer of Harvard Medical School reported 150 cases of fibrosarcoma treated with operations ranging from local excision to radical excision. Sixty-four patients (43%) developed local recurrence.(1) As with breast cancer, local recurrence was recognized as a grave sign. This encouraged more aggressive surgery.

    By the middle of the century surgeons at most major hospitals were performing amputations or very wide local excision. In 1948, Stout analyzed 218 cases of fibrosarcoma seen at Presbyterian Hospital in New York from 1907 to 1946.(2) Of 144 patients 86 (80%) were alive at last follow-up. Sixty-four patients (60%) developed local recurrence.

    In 1957, Lieberman and Ackerman reviewed 100 cases seen at Washington University and concluded,"The worst thing that can happen is local recurrence."(3) Many authors have presented supporting data, but most failed to consider the size and grade of the tumors.(4),(5),6)

    During the 1950's the treatment soft tissue sarcomas was very aggressive. This was also the period when the supraradical mastectomy for breast cancer was most popular.

    By the early 1960's surgeons began to change their ideas about local recurrence. In 1963, Atkinson at St. Vincent's Hospital Tumor Clinic became an early proponent of conservative management of soft tissue sarcomas.(7) He concluded,"An observation-only policy is advocated for those patients without local recurrence following enucleation or other similarly inadequate procedures."

    Limb-sparing surgery was initiated in the United States by Suit at M. D. Anderson Hospital in 1963. Lindberg et al. reported 300 patients treated with conservative surgery and postoperative radiotherapy between 1963 and 1977. Thirty-two of forty patients (80%), who developed extremity recurrences, were controlled by further surgery.(8) Lindberg carefully noted the effect of tumor grade and size on both local recurrence and survival. He concluded,"The incidence of distant metastases was not increased in patients who have had a local recurrence after this conservative approach."

    At the Massachusetts General Hospital Suit later analyzed 170 patients treated from 1971 to 1982 with conservative surgery and radiation therapy.(9) Twelve of the 19 patients with local recurrence were suitable for salvage surgery. Nine (75%) of these were alive and seven (56%) had no evidence of any disease one to three and a half years after the salvage procedure. In 1988, Suit reported that six of these patients had been disease-free for more than five years.(10)

    Leibel reviewed 81 patients with soft-tissue sarcomas of the extremity seen at the University of California, San Francisco from 1960 to 1978.(11) The development of distant metastases was independent of primary surgery or radiation. By the mid 1980's the American College of Surgeons and the National Cancer Institute had concluded that local recurrence did not adversely affect survival.(12),(13)

    In 1985, Potter et al. analyzed 358 patients with high-grade soft tissue sarcomas of the extremities treated with surgery and high dose radiation therapy at the NCI between 1975 and 1982.(14) Local excision resulted in local failure in 12 of 128 patients (9.3%). There were no local recurrences in patients treated with amputation. Nevertheless, there was no survival difference between the two groups. The authors concluded, "The significant salvage of patients with isolated, locally recurrent disease indicates that local failure is not necessarily a poor prognostic factor . . . "

    The many difficulties associated with retrospective studies can be reduced by multivariate analysis. The effects of tumor size and grade can be statistically isolated to study the possible effect of local recurrence on survival. Rooser of the University Hospital, Lund, Sweden, treated 325 patients with extremity sarcomas from 1964 to 1983.(15) Using the Cox proportional hazards model he considered the effects of margins of resection, tumor grade, tumor size and necrosis on local recurrence and survival. He said, "Local recurrence after surgery with a wide or radical margin is in many cases probably only a predictor of a grave prognosis and not the reason for metastasis." Rooser concluded,"However, for most patients prognosis seems to be determined already at the time of diagnosis of the primary tumor." Investigators from Lund also measured the interval from initial diagnosis to the time of metastasis, comparing patients with and without local recurrence.(16) Again, local recurrence did not appear to cause any additional metastases and was not an added threat to survival.<

    Ueda and associates from the Osaka University Medical School treated 163 patients with soft tissue sarcomas.(17) Patients were initially treated with marginal excision or wide local excision. There was a 73% local recurrence rate in the marginal excision group and a 10% recurrence rate among patients treated with wide excision. Radical surgery was utilized in 25 of 66 who developed recurrent disease. Using multivariate analysis they determined that initial surgical treatment did not influence ultimate survival. Ueda said his data supported the conclusion of others ". . . that local recurrence was not necessarily a poor prognostic sign in patients with localized STS."

    In 1985 Brennan and colleagues from the Memorial Sloan-Kettering Cancer Center concluded,". . . local recurrence did not appear to be a major determinant in survival. Current emphasis on local control may be much less important to survival than thought."(18) They analyzed 451 patients with soft-tissue sarcomas of the extremity treated from 1982 to 1987.(19) Multivariate analysis demonstrated that local recurrence did not affect survival. They also performed the first randomized, prospective trial of wide local excision and radiation therapy. They reported that brachytherapy enhanced the local control of soft-tissue sarcomas, but failed to improve survival.(20)

    In 1987, Collin reviewed the experience of Memorial Sloan-Kettering with 423 adults who had extremity sarcomas from 1968 to 1978.(21) Patients who had microscopically negative, but close (within millimeters) margins were classified as "marginal" resections. When compared to patients with adequate margins there was no survival difference. "Therefore, as long as the microscopic margins were negative, survival did not appear to be affected by increasing the soft tissue margins about the tumor." Collin concluded that local failure had an adverse impact on patient survival independent of tumor grade. Nevertheless, tumor size and margins of resection were not considered in assessing local recurrence as an independent risk factor. Patients with residual gross tumor did have a decreased survival, a reflection of tumor size.

    If local control has an independent effect to enhance survival, we should see this benefit among patients treated with radiation therapy. Unfortunately, this relationship does not occur. Most authorities report that radiation therapy improves local control, but does not affect survival.(22) Stotter et al. from the Royal Marsden Hospital in London concluded that local recurrence was a significant risk to survival.(23) They considered local recurrence as a "time-dependent" factor and reported that patients who developed local recurrence had 4.54 times the risk of developing distant metastases as those who did not. This analysis is similar to that of Fisher et al. who demonstrated that local recurrence after lumpectomy leads to a 3.41 greater risk of distant disease. Margolese found two types of local recurrence in the lumpectomy trial: 1) "persistence of residual disease," and 2) the "local manifestation of disseminated disease.(24) Fisher made an important distinction, local recurrence ". . . is a marker of risk for, not a cause of, distant metastasis."(25) Similarly, the local recurrence of soft tissue sarcoma may occur in two forms, the persistence of residual disease, and the manifestation of disseminated disease. Sixty percent of the patients in the Royal Marsden study had high grade tumors, and local recurrences appeared in 42% of these patients. Many of these recurrences were in patients who had already developed distant metastases. Stotter's findings do not contradict those summarized above. These two forms of local recurrence are more thoroughly discussed in Chapter 3 of our book..

    The suggestion that local recurrence has little affect on survival would have been heresy just a few years ago. But today wide local excision and radiation therapy are gaining acceptance in the treatment of soft tissue sarcoma. The central question is,"What is the clinical significance of local recurrence?" Specifically, does recurrent disease cause distant metastasis or is it merely a sign of aggressive disease? If local recurrence jeopardizes patient survival, then aggressive local control measures are indicated. Current evidence overwhelmingly suggests that local recurrence is merely a sign. It can be a sign that the tumor has already spread. It can also be a sign that the tumor is very aggressive. But if local recurrence is treated promptly, there is no reliable evidence that it causes the tumor spread. This observation supports the present trend toward limb preservation and should encourage surgeons and radiation therapists to strive toward an even greater concern for the functional and cosmetic results of their therapy.

    Medical References

    1. Warren S, Sommer GNJ. Fibrosarcoma of the soft parts with special reference to recurrence ad metastasis. Arch Surg 1936; 33: 425-450.

    2. Stout AP. Fibrosarcoma: the malignant tumor of fibroblasts. Cancer 1948; 3:30-63.

    3. Lieberman Z, Ackerman LV. Principles in management of soft tissue sarcomas. A clinical and pathological review of one hundred cases. Surgery 35: 350-365, 1954.

    4. Emrich L.J., Ruka W., Driscoll D.L., and Karakousis C.P. The effect of local recurrence on survival time in adult high-grade soft tissue sarcoma. J Clin Epidemiol, 1989, 42: 105-110.

    5. Cantin J., McNeer G.P., Chu F.C., and Booher R.J. The problem of local recurrence after treatment of soft tissue sarcoma. Ann Surg, 1968, 168: 47-53.

    6. Giuliano A.E., Eilber F.R., and Morton D.L. The management of locally recurrent soft-tissue sarcoma. Ann Surg, 1982, 196: 87-91.

    7. Atkinson L, Garvan JM, Newton NC. Behavior and management of soft connective tissue sarcomas. Cancer 1963; 16: 1552-1562.

    8. Lindberg RD, Martin RG, Romsdahl MM, Barkley HT. Conservative surgery and postoperative radiotherapy in 300 adults with soft-tissue sarcomas. Cancer 1981; 47: 2391-2397.

    9. Suit HD, Mankin HJ, Wood WC, Proppe KH. Preoperative, intraoperative, and postoperative radiation in the treatment of primary soft tissue sarcoma. Cancer 1985; 55: 2659-2667.

    10.  Suit HD, Mankin HJ, Wood WC, Gebhardt MC. Treatment of the patient with stage M0 soft tissue sarcomas. J Clin Oncol 1988; 6: 854-862.

    11.  Leibel SA, Tranbaugh RF, Wara WM, Beckstead JH, Bovill EG, Phillips TL. Soft-tissue sarcomas of the extremities. Survival and patterns of failure with conservative surgery and postoperative irradiation compared to surgery alone. Cancer 50: 1076-1083, 1982.

    12.  Lawrence W, Donegan W.L., Natarajan N, and others. Adult soft tissue sarcomas: a pattern of care survey of the American College of Surgeons.Ann Surg, 1987, 205: 349-359.

    13.  Potter DA, Kinsella T, Glatstein E et al. High-grade soft tissue sarcomas of the extremities. Cancer 1986; 58: 190-205.

    14.  Potter DA, Kinsella T, Glatstein E et al. High-grade soft tissue sarcomas of the extremities. Cancer 1986; 58: 190-205.

    15.  Rooser B. Prognosis in soft tissue sarcoma. Acta Orthop Scand (Sup. 225) 58: 1-52, 1987.

    16.  Gustafson P., Rooser B., Rydholm A. Is local recurrence of minor importance for metastases in soft tissue sarcoma? Cancer, 1991, 67: 2083-2086.

    17.  Ueda T, Aozasa K, Tsujimoto M. Hamada H, Hayashi H, Ono K, Matsumoto K. Multivariant analysis for clinical prognostic factors in 163 patients with soft tissue sarcoma. Cancer 62: 1444-1450, 1988.

    18.  Brennan MF, Shiu MH, Collin et al. Extremity soft tissue sarcomas. Cancer Treat Symp 3: 71-81, 1985.

    19.  Brennan MF: Management of extremity soft-tissue sarcoma. Am J Surg 158:71-78, 1989.

    20.  Brennan M.F., Casper E.S., Harrison L.B., and others. The role of multimodality therapy in soft-tissue sarcoma. Ann Surg, 1991, 214: 328-338.

    21. Collin C, Godbold J, Hajdu S, Brennan M. Localized extremity soft tissue sarcoma: An analysis of factors affecting survival. J Clin Oncol 5: 601-612, 1987.

    22.  Markhede G, Angervall L, Stener B. A multivariate analysis of the prognosis after surgical treatment of soft-tissue tumors. Cancer 49: 1721-1733, 1982.

    23.  Stotter A.T., A'Hern R.P., Fisher C., and others. The influence of local recurrence of extremity soft tissue sarcoma on metastasis and survival. Cancer, 1990, 65: 1119-1129.

    24.  Margolese RG. Recent trends in the management of breast cancer. 4. Diagnosis and management of local recurrence after breast-conservation surgery. Can J Surg 1992; 35:378-81.

    25. Fisher B., Anderson S., Fisher E.R., and others. Significance of ipsilateral recurrence after lumpectomy. Lancet, 1991, 338: 327-331.

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    Medical Research since 1995

    It has now been proven that conservative surgery alone is safe and effective treatment for most patients with soft tissue sarcoma. But, the scientific evidence is often buried by the prevailing prejudice against limited treatment. Many "leading" surgeons in this field still refuse to accept the innocent behavior of promptly-treated local recurrence. They recommend too much surgery and too much radiation therapy.

    Since 1995, two major randomized, prospective trials have published their updated results. W. T. Pisters and associates from the Memorial Sloan-Kettering Cancer Center conducted a trial of 164 patients, who were followed for over six years.(1) Local recurrence developed in 18 percent of those given radiation therapy and 29 percent of those who were not treated. The statistical five-year survival rates were statistically similar - 83 percent versus 80 percent, respectively. The authors concluded,"This improvement in local control does not have an impact on rates of distant recurrence or disease-specific survival."

    J. C. Yang and colleagues from the National Cancer Institute conducted a randomized trial of 141 patients, who were followed for over 9? years.(2) Local recurrence rates were lower in patients who received radiation, 1.4 percent for those given radiation therapy versus 23.9 percent for those who were not treated. There was no significant difference in the five-year survival rates. The authors said,"Thus the conclusions regarding adjuvant XRT (radiation) for patients with sarcoma are similar to conclusions reached for . . . primary breast cancer and rectal cancer, where local control was enhanced without significant differences in overall survival."

    Surgery without Radiation Therapy

    Some institutions have reported favorable experience using surgery alone without radiation therapy. C. P. Karakousis and associates of Roswell Park Cancer Institute in Buffalo New York, treated 116 with wide or radical resection.(3) Nine patients had an amputation. The local recurrence rate among these patients was 10 percent. The authors concluded,"Wide resection, when feasible, provides acceptable local control and may be preferable to local excision plus radiation therapy."

    C. P. Gibbs and colleagues of the University of Chicago analyzed 62 patients.(4) Fifty-nine patients (95 percent) went to Chicago for excision alone following limited surgery at a community hospital. Almost five years after treatment, only three patients - those treated with a narrow excision - had developed a local recurrence. The five-year survival rate - free of any cancer - was 85 percent. The authors concluded,"Excellent rates of survival . . . . can be obtained with carefully planned operative treatment alone."

    P.L. Fabrizio and associates from the Mayo Clinic in Rochester used surgery alone to treat 24 patients with localized extremity sarcoma.(5) They concluded,"It is appropriate to consider withholding irradiation for selected patients with low-grade tumors resected with a negative margins."

    Promptly-treated Local Recurrence Does Not Influence Survival

    P.M.F. Choong and associates from the University Hospital in Lund, Sweden, analyzed 134 locally recurrent tumors in patients who did not have metastatic disease.(6) They concluded that the clinical behavior of local recurrence is a better predictor of tumor behavior than the mere presence of local recurrence. Patients with aggressive primary tumors also had aggressive local recurrences and a shortened life expectancy. The local recurrence was an indicator of the poor prognosis - not its cause.

    A contrary point of view was expressed by C. S. Trovik and H. C. F. Bauer from the Karolinska Hospital in Stockholm, Sweden.(7) They analyzed their treatment of 379 patients. Among patients with favorable tumors (small size and/or low grade) local recurrence appeared to shorten survival. But, as discussed on page 73 and in the section on breast cancer in this appendix, it is statistically misleading to compare the survival of patients who develop local recurrence to the survival of those who do not.

    T. Ueda and colleagues updated their experience at the Osaka University Medical School. In a 1997 study, these investigators concluded,"Multivariate analysis showed that local recurrence after definitive surgery also lost its prognostic significance."(8) S. Singer and associates from Harvard studied 182 patients with extremity sarcomas from 1970 to 1992. (9) They concluded, "Thus, local recurrence does not appear to play a major role in influencing the overall survival."

    J. J. Lewis and associates analyzed 911 patients with soft tissue sarcomas of the extremity treated at Memorial Sloan-Kettering Cancer Center from 1982 to 1995.(10) Multivariate analysis demonstrated that local recurrence had no significant effect on survival. They concluded, "Clearly, local recurrence is not a source of metastasis." But, surgeons at Memorial have not embraced this concept and elsewhere their comments are not as clear. N. J. Espat and J. J. Lewis said, ". . . local tumor recurrence is associated with development of distant metastasis. . . . The relationship is an enigma. . . ."(11) Surgeons at Memorial appear to be confused about the relationship between local recurrence and survival. This confusion is further illustrated below.

    Perplexing Data from Memorial Sloan-Kettering Cancer Center

    M.F. Brennan of Memorial studied two groups of patients: 1) those who were first treated at Memorial Hospital (558 patients) and 2) those who were first treated elsewhere and came to Memorial with a local recurrence (318 patients).(12) All patients had their tumors removed and following surgery the local recurrence rates were similar in both groups. But then Brennan found a surprise. He found that patients who were first treated at a community hospital lived significantly longer than those first treated at Memorial. The five-years survival rates were approximately 80 percent (first treatment elsewhere) versus 55 percent (first treatment at Memorial). Brennan said this information "further obfuscates the problem (of understanding local recurrence)."

    Those who are following the theme of this book will find nothing surprising about Brennan's results. Some patients treated at community hospitals died of their disease. (There immune system lost its initial battle against the tumor.) Others who were referred to Memorial may have had a local recurrence, but they were free of apparent distant disease. Their immune system had already prevented the distant spread of tumor cells. They had won their first battle with their cancer and were immunologically strong enough to win the second battle with their local recurrence. In contrast, the group of patients who were first treated at Memorial included some patients with a relatively weak immune system. Their early death decreased the overall survival of this group. Thus, patients who were first treated at a community hospital had an overall survival rate which was greater than that of patients who received their first treatment at Memorial.

    Texas Cancer Center Treatment Analysis

    The Texas Cancer Center supports the increased use of conservative surgery in the treatment of soft tissue sarcomas. The Texas Cancer Center also supports the position of the NSABP that local recurrence is a marker for distant metastasis, not its cause. Promptly-treated local recurrence does not spread.

    Medical References since 1995

    1. Pisters PWT, Harrison LB, Leung DHY, Woodruff JM, Casper ES, Brennan MF. Long-term results of a prospective randomized trial of adjuvant brachytherapy in soft tissue sarcoma. J Clin Oncol 14:859-868, 1996.

    2. Yang JC, Chang AE, Baker R, Sindelar WF, Danforth DN, and others. Randomized prospective study of the benefit of adjuvant radiation therapy in the treatment of soft tissue sarcoma of the extremity. J Clin Oncol 16:197-203, 1998.

    3. Karakousis CP, Proimakis C, Walsh DL. Primary soft tissue sarcoma of the extremities in adults. Br J Surg 82:1208-1212, 1995.

    4. Gibbs CP, Peabody TD, Mundt AJ and others. Oncological outcomes of operative treatment of subcutaneous soft-tissue sarcomas of the extremities. J Bone Joint Surg Ann 79:888-897, 1997.

    5. Fabrizio PL, Stafford SL, Pritchard DJ. Extremity soft-tissue sarcomas selectively treated with surgery alone. Int J Radiat Oncol Biol Phys 48:227-232, 2000.

    6. Choong PFM, Gustafson P, Rydholm A. Size and timing of local recurrence predicts metastasis in soft tissue sarcoma. Acta Orthop Scand 66:147-152, 1995.

    7. Trovik CS and Bauer HCF Bauer. Local recurrence of soft tissue sarcoma a risk factor for late metastases. Acta Orthop Scand 65:553-558, 1994.

    8. Ueda T, Toshikawa H, Mori S, Myoui A, Kuratsu S, Uchida A. Influence of local recurrence of the prognosis of soft-tissue sarcoma. J Bone Joint Surg (Br) 79:B:553-557, 1997.

    9. Singer S, Corson JM, Gonin R, Labow B, Eberlein TJ. Prognostic factors predictive of survival and local recurrence for extremity soft tissue sarcoma. Ann Surg 219:165-173, 1994.

    10. Lewis JJ, Leung D, Heslin M, Woodruff JM, Brennan MF. Association of local recurrence with subsequent survival in extremity soft tissue sarcoma. J Clin Oncol 15:646-52, 1997.

    11. Espat NJ and Lewis JJ. The biological significance of failure at the primary site on ultimate survival in soft tissue sarcoma. Semin Radiat Oncol 9:369-377, 1999.

    12.. The enigma of local recurrence. Ann Surg Oncol 4:1-12, 1997.

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