Major Upper-Limb Amputations for Malignant Tumors

SCIENTIFIC ARTICLE

Major Upper-Limb Amputations for Malignant Tumors Mark E. Puhaindran, MBBS, Joanne Chou, MPH, Jonathan A. Forsberg, MD, Edward A. Athanasian, MD

Purpose With the continued advancement of limb salvage surgery, major upper-limb amputations are being performed less frequently and are generally reserved for patients with large, multifocal, or recurrent tumors for whom limb salvage is no longer an option. We conducted a retrospective review of the current indications and patient outcomes after major upper-limb amputations for malignant tumors. Methods Using the institution surgical database, we identified 43 patients who underwent major upper-limb amputation for primary and metastatic malignant tumors from 1996 to 2008. Results Of these 43 patients, 25 had soft tissue sarcoma, 7 had bone sarcoma, and 11 had carcinoma. Two patients had stage I, 3 had stage II, 21 had stage III, and 17 had stage IV disease. We performed 45 amputations: 5 below the elbow, 14 above the elbow, and 26 at the forequarter. Among the 45 amputations, 2 patients underwent a second more proximal amputation for local tumor recurrence. Of the 17 patients with stage IV disease, 10 underwent palliative amputation for symptom control. A total of 28 patients (65%) died. Median survival after amputation was 13 months (95% confidence interval, 8 –19 mo). The 6-month cumulative incidence of local recurrence was 22%. Overall survival after forequarter amputations was 42% at 1 year. Conclusions Survival after major upper-limb amputation is poor, especially because amputations are reserved for patients with advanced tumors. However, amputation remains an option for local tumor control and can palliate symptoms in selected patients. Improvement of survival requires more effective systemic treatment strategies. (J Hand Surg 2012;37A:1235–1241. Copyright © 2012 by the American Society for Surgery of the Hand. All rights reserved.) Type of study/level of evidence Therapeutic IV. Key words Amputation, malignant tumors, outcomes, survival, upper limb. of the upper limb (amputations at or proximal to the wrist joint) has historically been poor, because these amputations are frequently reserved for patients with large or multifocal tumors for whom limb salvage is not possible, or for palliation of symptoms in patients with metastatic disease.1–17 Even in recurrent tumors, ampu-

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URVIVAL AFTER MAJOR AMPUTATIONS

FromtheDepartmentofHandandReconstructiveMicrosurgery,NationalUniversityHospital,Singapore; the Department of Biostatistics and Epidemiology, Memorial Sloan-Kettering Cancer Center, New York, NY; the Department of Orthopaedic Oncology, National Military Medical Center, Bethesda, MD; the Orthopaedic Service, Memorial Sloan-Kettering Cancer Center and the Hand Surgery Service, Hospital for Special Surgery, New York, NY.

tation is typically performed only when limb preservation is no longer possible.15,16 One reason why major upper-limb amputations are avoided is that, unlike lower limb prostheses, upperlimb prostheses are inadequate aesthetic and functional substitutes for the native limbs.18 –20 This is highlighted by the fact that amputees frequently abandon use of Corresponding author: Mark E. Puhaindran, MBBS, Department of Hand and Reconstructive Microsurgery,NationalUniversityHospital,1E,KentRidgeRoad,NUHSTowerBlock,Level11,Singapore 119228, Singapore; e-mail: [email protected]. 0363-5023/12/37A06-0022$36.00/0 doi:10.1016/j.jhsa.2012.02.004

Received for publication August 17, 2011; accepted in revised form February 2, 2012. No benefits in any form have been received or will be received related directly or indirectly to the subject of this article.

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upper-limb prostheses.21 Microsurgical free tissue transfer has increased the opportunities for limb salvage. The indications for amputation have also changed with resection-replantation, which has been performed in a select group of patients, with acceptable results.22,23 For these reasons, major upper-limb amputations for malignant tumors are reserved for only those patients for whom resection and reconstruction are not viable options. We conducted this review to assess recent outcomes after major upper-limb amputations for malignant tumors, which could have been affected by advances in imaging, surgery, chemotherapy, and radiotherapy. We examined overall survival for patients with all tumor types undergoing major upper-limb amputation and local recurrence rate, defined as recurrence within the same limb or amputation stump. We also reviewed the indications for amputation in this group of patients. MATERIALS AND METHODS We conducted this study using the institution surgical database, with institutional review board approval. We retrospectively reviewed the records and analyzed clinical outcomes for all patients who had undergone major upper-limb amputations for primary or metastatic disease for all malignant tumor types from 1996 to 2008 at our center. Patients were observed from the date of surgery to death or latest review. We used the American Joint Committee on Cancer Staging System24 to stage the tumors based on the staging criteria for the respective tumors. We calculated overall survival (OS) from the date of primary surgery to death or the date of last follow-up. We estimated OS using Kaplan-Meier methods and compared survival probability using the log-rank test. Time to recurrence was calculated from primary surgery to date of recurrence. We used the cumulative incidence function to estimate the probability of time to local recurrence in which death without a recurrence (n ⫽ 18) was considered a competing event. RESULTS We identified 43 patients, 45 of whom had had major upper-limb amputations performed. Among them were 2 patients who had undergone a second, more proximal amputation following tumor recurrence after an initial amputation. Indications for amputation included large or multifocal tumors, primary or recurrent, that involved the blood vessels or nerves (n ⫽ 33), for which local resection was not possible or would have resulted

in a functionless and insensate extremity. Palliative amputations were done for patients who had symptoms that included fungating tumors (n ⫽ 7), severe pain owing to nerve invasion (n ⫽ 1), and an enlarged functionless limb resulting from severe chronic lymphedema after failed treatment with other surgical and nonsurgical modalities (n ⫽ 2). We included all patients in our analysis (those undergoing therapeutic amputations and those having it done for symptom palliation) despite the expected difference in outcomes, because we wanted to assess the overall outcomes for the entire cohort of patients for whom such a drastic surgery had been undertaken. The mean age of patients at the time of surgery was 60 years (SD, 16.9 y). The histological diagnosis was sarcoma in 32 patients: soft tissue sarcoma in 25 patients, bone sarcoma in 7 (3 chondrosarcoma and 4 osteogenic sarcoma), and carcinoma in 11 (6 squamous cell carcinoma, 3 non–small cell lung cancer, 1 breast carcinoma, and 1 cervical adenocarcinoma). In the patients with carcinoma, we performed 10 of 11 amputations for metastatic deposits. The American Joint Committee on Cancer stages were stage I in 2 patients, stage II in 3 patients, stage III in 21 patients, and stage IV in 17 patients. We performed amputation for 28 (65%) patients who had tumors that recurred within the same limb or surgical site after previous limb preserving resections. We performed 5 below-elbow, 14 above-elbow, and 26 forequarter amputations. Among the 17 patients with stage IV disease, 7 underwent attempted curative amputations followed by resection of the metastases at a second stage, whereas 10 patients underwent amputation primarily for symptom palliation. Nine patients underwent perioperative chemotherapy, and 5 underwent radiotherapy. In these patients, we customized the decision for adjuvant chemotherapy or radiation because they all had locally aggressive or recurrent disease that excluded them from treatment on protocols. Table 1 provides detailed patient characteristics. A total of 28 patients died. Median follow-up for survivors was 14 months. The 1-year survival rate was 55% (95 confidence interval [CI], 38% to 70%). Median survival was 13 months (95% CI, 8 –19 mo) (Fig. 1). There was no difference in survival between patients with stage IV disease who underwent amputation with therapeutic intent and those who had amputation for symptom palliation. For patients undergoing forequarter amputations, 1-year OS was 42% (95% CI, 22% to 60%), and the 2-year OS was less than 20%. Thirteen patients in this series developed local tumor recurrence, and the 6-month cumulative incidence for local recurrence was 22% (Fig. 2).

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TABLE 1.

Patient Summary

Sex

Histology

Amputation Level

AJCC Stage

Indication

Chemotherapy

Radiotherapy

Margins

Local Recurrence

Status

1 2a 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38

43 83 51 35 49 36 53 83 56 77 67 79 70 70 26 64 72 72 41 67 64 71 84 65 53 68 55 66 66 40 33 65 76 76 36 35 67 76

F F M F M M F F M F F M M M M F M F F F F F F M F M M M F F M M F M M F M F

STS STS NSCLC OGS STS OGS Breast cancer STS STS STS STS SCC STS STS STS STS SCC STS STS OGS Chondrosarcoma STS STS STS SCC SCC NSCLC Chondrosarcoma SCC Cervical cancer STS Chondrosarcoma STS STS OGS STS NSCLC STS

BE AE FQ AE FQ FQ FQ AE AE AE FQ FQ FQ FQ FQ AE AE FQ AE FQ FQ AE FQ BE AE FQ FQ FQ FQ FQ FQ FQ BE FQ FQ FQ AE AE

1 3 4 4 3 2 3 3 3 4 3 3 3 4 3 3 4 4 3 3 2 3 4 3 3 4 4 2 3 4 3 4 1 4 4 3 4 4

Therapeutic Therapeutic Palliative Therapeutic Therapeutic Therapeutic Therapeutic Therapeutic Therapeutic Palliative Therapeutic Therapeutic Therapeutic Palliative Therapeutic Therapeutic Therapeutic Palliative Therapeutic Therapeutic Therapeutic Therapeutic Therapeutic Therapeutic Therapeutic Palliative Palliative Therapeutic Therapeutic Palliative Therapeutic Therapeutic Therapeutic Palliative Therapeutic Therapeutic Therapeutic Therapeutic

No No No Yes No Yes No No Yes No Yes No No Yes No No Yes No No No No No Yes No Yes No No No No No No No No No No No No No

No No Yes No Yes No No No No No No No Yes No No No No No No No No No No No No No No Yes Yes No No No No No No No No No

Negative Negative Positive Negative Positive Negative Positive Negative Negative Negative Negative Negative Negative Positive Negative Negative Negative Negative Negative Negative Negative Negative Negative Negative Negative Negative Negative Negative Negative Negative Negative Positive Negative Negative Positive Positive Negative Negative

No Yes No No Yes No No No No No Yes Yes No No No No Yes Yes No No No No Yes No No No No No No No Yes Yes Yes No No Yes No No

NED Dead Dead Dead Dead NED Dead NED Dead Dead Dead Dead NED Dead AWD NED AWD Dead NED NED NED NED Dead NED Dead Dead Dead Dead Dead Dead Dead Dead AWD Dead Dead Dead NED Dead

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Patient No.

Age at Surgery (y)

Dead Dead NED Dead Dead Negative Negative Negative Negative Negative 4 3 3 3 4 29 51 46 71 83 39 40 41a 42 43

M M F F M

STS STS STS SCC STS

FQ FQ BE BE FQ

Palliative Therapeutic Therapeutic Therapeutic Palliative

No Yes No No No

No No No No No

No Yes Yes No No

Status Local Recurrence Margins Radiotherapy Chemotherapy Indication AJCC Stage Amputation Level Histology Patient No.

Sex Age at Surgery (y)

Patient Summary (Continued) TABLE 1.

AJCC, American Joint Committee on Cancer; STS, soft tissue sarcoma; OGS, osteogenic sarcoma; NSCLC, non–small cell lung cancer; SCC, squamous cell carcinoma; BE, below-elbow amputation; AE, above-elbow amputation; FQ, forequarter amputation; AWD, alive with disease; NED, no evidence of disease. a Patients underwent second amputation (both above-elbow amputations) after local recurrence of tumor.

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FIGURE 1: Overall survival for all patients undergoing major upper-limb amputations.

FIGURE 2: Cumulative incidence of local recurrence and death without local recurrence for patients.

DISCUSSION We conducted this review to assess recent outcomes after major upper-limb amputations for malignant tumors. Its retrospective nature, small patient numbers, and great variation in cancer diagnoses were limitations. We were unable to generate specific guidelines for amputation because a combination of various factors often led to the recommendation for amputation. The small numbers also meant that a meaningful analysis of survival for individual tumor types or the factors associated with tumor local or distant recurrence after amputation could not be performed. JHS 䉬 Vol A, June 

TABLE 2.

Published Series on Forequarter Amputations With at Least 10 Patients Year

No.

Distant Metastasesa

Recurrent Tumorb

Curative

1969

105

Not stated

Not stated

94 (90%)

11 (10%)

STS: 37 BS: 27 Mel: 16 SCC: 8 Met CA: 11 (4 ⫻ breast) Rad Ulc: 3 Des: 3

Not stated

15 (14%) surviving ⬎5 y 44 (42%) lost to followup

Not stated

Fanous et al5

1976

21

0

9 (43%)

19 (90%)

2 (10%)

STS: 9 BS: 6 Mel: 2 SCC: 2 Met CA: 2 (2 ⫻ breast)

3 (14%)

4 (19%) surviving ⬎5 y

1–168 mo

Sim et al14

1977

175

Not stated

Not stated

Not stated

Not stated

STS: 68 BS: 85 Mel: 5 SCC: 11 Met CA: 4 Lym: 2

Not stated

33 (19%) surviving ⬎5 y

1 to ⬎120 mo

Levine et al9

1994

10

0

6 (60%)

10 (100%)

0

STS: 6 Mel: 1 Des: 3

1 (10%)

100% at latest follow-up (2 alive with distant mets)

2–184 mo

Bhagia et al1

1997

20

5 (25%)

3 (15%)

15 (75%)

5 (25%)

STS: 4 BS: 14 Met CA: 2

2 (10%)

5-y OS, 21% 5-y OS (curative), 30%

1–177 mo

Reference el-Domeiri and Miller

4

2001

12

12 (100%)

10 (83%)

Rickelt et al12

2009

40

8 (20%)

0

Histology

Local Recurrence

Survival

Follow-up

MAJOR UPPER-LIMB AMPUTATIONS

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Merimsky et al10

Palliative

Palliative, 21 mo (median)

12 (100%)

STS: 5 BS: 2 SCC: 2 Met STS: 1 Met CA: 2 (1 ⫻ breast)

3 (25%)

9 (75%) dead of disease within 3–24 mo Median, 8 mo

3–24 mo

32 (80%)

8 (20%)

STS: 22 BS: 6 Melanoma: 3 BCC: 1 Met CA: 6 (5 ⫻ breast) Rad Ulc: 2

8 (20%) Median 4 mo, range 1–19 mo

1-y OS, 71% 2-y OS, 59% 5-y OS, 38% Palliative, 5 mo (median)

1–184 mo (median, 16 mo)

(Continued)

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Known distant metastases at the time of amputation. Amputation done after local recurrence of a tumor. Des, desmoid tumor; OS, overall survival; BS, bone sarcoma; Mel, melanoma; SCC, squamous cell carcinoma; STS, soft tissue sarcoma; Met CA, metastatic carcinoma; Met STS, metastatic soft tissue sarcoma; Rad Ulc, radiation ulcer; Lym, lymphoma. b

Current series

a

1–54 mo (median, 8 mo) 1-y OS, 42% 2-y OS, ⬍20% Palliative, 8 mo (median) 9 (35%) Median 6 mo, range 1–9 mo 26

12 (46%)

62%

17 (65%)

9 (35%)

STS: 13 Bone: 6 SCC: 2 Met CA: 5 (1 ⫻ breast)

Survival Local Recurrence Histology Palliative Curative Recurrent Tumorb Distant Metastasesa No. Year Reference

TABLE 2.

Published Series on Forequarter Amputations With at Least 10 Patients (Continued)

Follow-up

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We found no difference between outcomes in patients with stage IV disease who underwent amputation with therapeutic intent and those who underwent the procedure for symptom palliation. Despite the small patient numbers, this brings into question the utility of performing these drastic operations in patients with stage IV disease for reasons other than symptom palliation. Even when we performed amputation, the final surgical option for local tumor control, the 6-month cumulative incidence of local recurrence for the entire cohort was 22%. Therefore, patients should be carefully counseled before an amputation is performed. Our survival outcomes for forequarter amputations appear worse than those previously published1,4,5,9,10,12,14 (Table 2). Although the earlier series did not use the Kaplan-Meier method to estimate overall survival,4,5,9,14 it appears that better overall survival was achieved with at least 14%4 of the original cohort of patients surviving 5 years. This percentage could be higher because 42% of patients were lost to follow-up. Our results also appear poorer than those published more recently,1,12 with the exception of the cohort of patients studied by Merimsky et al.10 However, all patients in that series had metastatic disease when they underwent palliative forequarter amputation. The poor patient survival in our study probably resulted from the large number of patients with distant metastases at the time of forequarter amputation (12 of the 26 patients; 46%). Because amputation only helps with local control of the disease, improvement in survival for patients with systemic disease may only be achieved when more effective systemic treatment strategies become available. The trend toward poor outcomes after recent major upper-limb amputations could be accounted for by the more advanced extent of patients’ disease. It may be thought of as the opposite of stage migration25 because, with the widening of the scope for limb salvage, only patients with the most difficult or extensive tumors are being treated with amputation. We reserved upper extremity major amputations in the current series for palliation of symptoms or as a last resort for large tumors in which limb preservation was not possible. This trend has been demonstrated at our center for soft tissue sarcomas, the most common tumor type for which upper extremity amputations were performed. Extremity amputations as a percentage of total soft tissue sarcoma patients at our center have decreased from 32% between 1968 and 1978 to 14% between 1982 and 1990,16 and to 5% in this series between 1996 and 2008. Between 1982 and 2000, amputation was also done only for 9% of patients, even for locally recurrent tumors.15 Although survival after major upper-limb JHS 䉬 Vol A, June 

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amputation is poor and our results may not affect the current indications for major upper-limb amputation, the results will help us better advise patients preoperatively about the expected outcomes. REFERENCES 1. Bhagia SM, Elek EM, Grimer RJ, Carter SR, Tillman RM. Forequarter amputation for high-grade malignant tumours of the shoulder girdle. J Bone Joint Surg 1997;79B:924 –926. 2. Blader S, Gunterberg B, Markhede G. Amputation for tumor of the upper arm. Acta Orthop Scand 1983;54:226 –229. 3. Clark MA, Thomas JM. Major amputation for soft-tissue sarcoma. Br J Surg 2003;90:102–107. 4. el-Domeiri AA, Miller TR. The role of interscapulothoracic amputation in the treatment of malignant tumors. Surg Gynecol Obstet 1969;129:1203–1206. 5. Fanous N, Didolkar MS, Holyoke ED, Elias EG. Evaluation of forequarter amputation in malignant diseases. Surg Gynecol Obstet 1976;142:381–384. 6. Hardin CA. Interscapulothoracic amputation for sarcomas of the upper extremity. Surgery 1961;49:355–358. 7. Holleb AI, Lucas JC Jr. Palliative interscapulothoracic amputation in the management of the breast cancer patient. Cancer 1959;12:643– 647. 8. Johnston EA, Namm JP, Reeves ME. Major extremity amputation for nodal metastasis from squamous cell carcinoma. J Surg Oncol 2006;93:76 –78; discussion 78 –79. 9. Levine EA, Warso MA, McCoy DM, Das Gupta TK. Forequarter amputation for soft tissue tumors. Am Surg 1994;60:367–370. 10. Merimsky O, Kollender Y, Inbar M, Lev-Chelouche D, Gutman M, Issakov J, et al. Is forequarter amputation justified for palliation of intractable cancer symptoms? Oncology 2001;60:55–59. 11. Pack GT. Major exarticulations for malignant neoplasms of the extremities: interscapulothoracic amputation, hip-joint disarticulation, and interilio-abdominal amputation; a report of end results in 228 cases. J Bone Joint Surg 1956;38A:249 –262. 12. Rickelt J, Hoekstra H, van Coevorden F, de Vreeze R, Verhoef C, van Geel AN. Forequarter amputation for malignancy. Br J Surg 2009;96:792–798.

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13. Roy P, Clark MA, Thomas JM. Stewart-Treves syndrome—treatment and outcome in six patients from a single centre. Eur J Surg Oncol 2004;30:982–986. 14. Sim FH, Pritchard DJ, Ivins JC. Forequarter amputation. Orthop Clin North Am 1977;8:921–931. 15. Stojadinovic A, Jaques DP, Leung DH, Healey JH, Brennan MF. Amputation for recurrent soft tissue sarcoma of the extremity: indications and outcome. Ann Surg Oncol 2001;8:509 –518. 16. Williard WC, Collin C, Casper ES, Hajdu SI, Brennan MF. The changing role of amputation for soft tissue sarcoma of the extremity in adults. Surg Gynecol Obstet 1992;175:389 –396. 17. Wittig JC, Bickels J, Kollender Y, Kellar-Graney KL, Meller I, Malawer MM. Palliative forequarter amputation for metastatic carcinoma to the shoulder girdle region: indications, preoperative evaluation, surgical technique, and results. J Surg Oncol 2001;77:105– 113; discussion 114. 18. Graham B, Adkins P, Tsai TM, Firrell J, Breidenbach WC. Major replantation versus revision amputation and prosthetic fitting in the upper extremity: a late functional outcomes study. J Hand Surg 1998;23A:783–791. 19. Peacock K, Tsai TM. Comparison of functional results of replantation versus prosthesis in a patient with bilateral arm amputation. Clin Orthop Relat Res 1987:153–159. 20. Wright TW, Hagen AD, Wood MB. Prosthetic usage in major upper extremity amputations. J Hand Surg 1995;20A:619 – 622. 21. Biddiss EA, Chau TT. Upper limb prosthesis use and abandonment: a survey of the last 25 years. Prosthet Orthot Int 2007;31:236 –257. 22. Athanasian EA, Healey JH. Resection replantation of the arm for sarcoma: an alternative to amputation. Clin Orthop Relat Res 2002: 204 –208. 23. Windhager R, Millesi H, Kotz R. Resection-replantation for primary malignant tumours of the arm. An alternative to fore-quarter amputation. J Bone Joint Surg 1995;77B:176 –184. 24. Greene FL, American Joint Committee on Cancer, American Cancer Society. AJCC cancer staging manual. New York: Springer-Verlag, 2002. 25. Feinstein AR, Sosin DM, Wells CK. The Will Rogers phenomenon. Stage migration and new diagnostic techniques as a source of misleading statistics for survival in cancer. N Engl J Med 1985;312: 1604 –1608.

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