Does referral to a specialist centre improve outcomes?

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Does referral to a specialist centre improve outcomes in BSTTs?

Introduction

It is estimated that a busy general practitioner will only see one to two patients with sarcoma in their clinical practice lifetime.[1][2][3]. National registries also reveal that a general orthopaedic surgeon can expect to see less than one patient with a primary bone tumour every three years.[4][5] Figures do not exist for the rates of sarcoma patients seen initially by other types of surgeon.

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Referral to specialist centres

As it will never be possible to conduct a randomised trial on this topic evidence can only be gained from analysis of series of patients treated within and outside specialist centres. This leads to significant bias in the cases reported as those patients with a good prognosis (for example a patient with a superficial tumour that is readily widely excised) are often not referred whereas those with complex treatment requirements or suspected poorer prognosis are.[6] However, even with these caveats published series consistently report that outcomes are worse when treatment is initiated in non-specialist centres.[5][7][8][9][10][11][12] Unfortunately, current estimates are that up to half of all patients with soft-tissue sarcoma (STS) are managed outside specialist centres.[1]

As sarcomas are rare, but benign soft tissue tumours are very common, surgery is often undertaken with a plan to perform enucleation or marginal excision. This usually occurs prior to any imaging or biopsy.[13][14][15] These procedures have come to be known as “unplanned surgery”.[16] There is residual tumour found at re-excision in 39-68% of these patients.[17][18][19][20] Re-excision is often a more complex and complicated procedure and the chance for optimal treatment may have been lost by unplanned surgery.[2][21][22][23][24][25] Reported local recurrence rates after unplanned surgery are in the range of 60 to 90%.[16][26][6][27][28] There is also evidence that disease-specific survival is higher in patients treated in specialist centres.[29][30][2][10][6][18]

Reported series often only consider a few of the possible outcomes of non-referral for specialist treatment. These include the effect of delayed diagnosis, the need for repeated procedures and ultimately the effects on local and distant recurrence.

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Evidence summary and recommendations

Evidence summary Level References
The rate of preoperative diagnosis in non-specialist centres ranges from 17-60%. This greatly increases the chances of incomplete resection. IV [13], [14], [15], [31]
When biopsies are performed in non-specialist units the errors in diagnosis, non-representative samples and biopsy site complications resulting in alterations in treatment or outcome, have been shown to be between 2–12 times greater than when the biopsy is performed in a specialist centre. Referral of patients to specialist centres results in less unplanned surgery and fewer biopsy-related complications. IV [5], [7], [8], [9], [10], [11], [12], [31]
The rates of positive excision margins in patients treated in non-specialist centres are often reported to be as high as 67-93%. Specialist centres generally report rates below 35%. IV [13], [14], [21], [5], [15], [4], [22], [16], [31]
Reoperation reveals residual disease in 39-68% of patients referred after their primary excision. Current imaging modalities are unable to reliably predict the presence of residual microscopic disease. III-2, IV [10], [4], [15], [17], [18], [19], [20]
Reoperation becomes increasingly complex due to inappropriately placed incisions, contamination of uninvolved tissue planes and wound complications. The costs associated with treatment are significantly increased. IV [17], [21], [23], [2], [24], [22], [25], [19]
Treatment recommendations by the referring physician have been reported to cause anxiety and confusion as they agree with the recommendation of specialists on less than 50% of occasions. IV [17]
Local recurrence rates are higher following incomplete primary excision. Rates in non-specialist units are generally two to four times higher than those achieved in specialist centres. III-2, IV [27], [23], [18], [28], [13], [29], [7], [2], [19], [26]
Disease-specific survival is greater in patients treated in specialist centres. III-2, IV [18], [2], [6], [15], [29], [10], [30], [32]
Evidence-based recommendationQuestion mark transparent.png Grade
Patients with suspected sarcoma to be referred to a specialist sarcoma unit prior to diagnosis in order to reduce the rates of incomplete excision, reoperation, local recurrence and to improve survival.
C


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Issues requiring more clinical research study

  • What are the economic implications of referral and non-referral for specialist care?


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References

  1. 1.0 1.1 Clinical Governance Research and Development Unit (CGRDU), Department of Health Sciences, University of Leicester. Referral Guidelines for Suspected Cancer in Adults and Children (Internet). National Institute for Health and Clinical Excellence: Guidance 2005 Jun Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21473024.
  2. 2.0 2.1 2.2 2.3 2.4 2.5 Abellan JF, Lamo de Espinosa JM, Duart J, Patiño-García A, Martin-Algarra S, Martínez-Monge R, et al. Nonreferral of possible soft tissue sarcomas in adults: a dangerous omission in policy. Sarcoma 2009;2009:827912 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20066170.
  3. Pencavel TD, Strauss DC, Thomas GP, Thomas JM, Hayes AJ. Does the two-week rule pathway improve the diagnosis of soft tissue sarcoma? A retrospective review of referral patterns and outcomes over five years in a regional sarcoma centre. Ann R Coll Surg Engl 2010 Jul;92(5):417-21 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20487596.
  4. 4.0 4.1 4.2 Randall RL, Bruckner JD, Papenhausen MD, Thurman T, Conrad EU 3rd. Errors in diagnosis and margin determination of soft-tissue sarcomas initially treated at non-tertiary centers. Orthopedics 2004 Feb;27(2):209-12 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/14992389.
  5. 5.0 5.1 5.2 5.3 Elliott RS, Flint M, French G. Refer prior to biopsy of suspected appendicular soft tissue sarcoma. N Z Med J 2012 Nov 23;125(1366):12-9 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/23254522.
  6. 6.0 6.1 6.2 6.3 Lewis JJ, Leung D, Espat J, Woodruff JM, Brennan MF. Effect of reresection in extremity soft tissue sarcoma. Ann Surg 2000 May;231(5):655-63 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/10767786.
  7. 7.0 7.1 7.2 Gustafson P, Dreinhöfer KE, Rydholm A. Soft tissue sarcoma should be treated at a tumor center. A comparison of quality of surgery in 375 patients. Acta Orthop Scand 1994 Feb;65(1):47-50 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/8154283.
  8. 8.0 8.1 Mankin HJ, Lange TA, Spanier SS. The hazards of biopsy in patients with malignant primary bone and soft-tissue tumors. J Bone Joint Surg Am 1982 Oct;64(8):1121-7 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/7130225.
  9. 9.0 9.1 Mankin HJ, Mankin CJ, Simon MA. The hazards of the biopsy, revisited. Members of the Musculoskeletal Tumor Society. J Bone Joint Surg Am 1996 May;78(5):656-63 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/8642021.
  10. 10.0 10.1 10.2 10.3 10.4 Chandrasekar CR, Wafa H, Grimer RJ, Carter SR, Tillman RM, Abudu A. The effect of an unplanned excision of a soft-tissue sarcoma on prognosis. J Bone Joint Surg Br 2008 Feb;90(2):203-8 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/18256089.
  11. 11.0 11.1 Grimer R, Athanasou N, Gerrand C, Judson I, Lewis I, Morland B, et al. UK Guidelines for the Management of Bone Sarcomas. Sarcoma 2010;2010:317462 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21253474.
  12. 12.0 12.1 Malhas AM, Sumathi VP, James SL, Menna C, Carter SR, Tillman RM, et al. Low-grade central osteosarcoma: a difficult condition to diagnose. Sarcoma 2012;2012:764796 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/22851905.
  13. 13.0 13.1 13.2 13.3 Bauer HC, Trovik CS, Alvegård TA, Berlin O, Erlanson M, Gustafson P, et al. Monitoring referral and treatment in soft tissue sarcoma: study based on 1,851 patients from the Scandinavian Sarcoma Group Register. Acta Orthop Scand 2001 Apr;72(2):150-9 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/11372946.
  14. 14.0 14.1 14.2 Clasby R, Tilling K, Smith MA, Fletcher CD. Variable management of soft tissue sarcoma: regional audit with implications for specialist care. Br J Surg 1997 Dec;84(12):1692-6 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/9448617.
  15. 15.0 15.1 15.2 15.3 15.4 Funovics PT, Vaselic S, Panotopoulos J, Kotz RI, Dominkus M. The impact of re-excision of inadequately resected soft tissue sarcomas on surgical therapy, results, and prognosis: A single institution experience with 682 patients. J Surg Oncol 2010 Nov 1;102(6):626-33 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20886550.
  16. 16.0 16.1 16.2 Giuliano AE, Eilber FR. The rationale for planned reoperation after unplanned total excision of soft-tissue sarcomas. J Clin Oncol 1985 Oct;3(10):1344-8 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/4045526.
  17. 17.0 17.1 17.2 17.3 Siegel HJ, Brown O, Lopez-Ben R, Siegal GP. Unplanned surgical excision of extremity soft tissue sarcomas: patient profile and referral patterns. J Surg Orthop Adv 2009;18(2):93-8 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/19602337.
  18. 18.0 18.1 18.2 18.3 18.4 Qureshi YA, Huddy JR, Miller JD, Strauss DC, Thomas JM, Hayes AJ. Unplanned excision of soft tissue sarcoma results in increased rates of local recurrence despite full further oncological treatment. Ann Surg Oncol 2012 Mar;19(3):871-7 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21792512.
  19. 19.0 19.1 19.2 19.3 Manoso MW, Frassica DA, Deune EG, Frassica FJ. Outcomes of re-excision after unplanned excisions of soft-tissue sarcomas. J Surg Oncol 2005 Sep 1;91(3):153-8 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/16118773.
  20. 20.0 20.1 Zagars GK, Ballo MT. Sequencing radiotherapy for soft tissue sarcoma when re-resection is planned. Int J Radiat Oncol Biol Phys 2003 May 1;56(1):21-7 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/12694820.
  21. 21.0 21.1 21.2 Zacherl M, Kastner N, Glehr M, Scheipl S, Schwantzer G, Koch H, et al. Influence of prereferral surgery in soft tissue sarcoma: 10 years' experience in a single institution. Orthopedics 2012 Aug 1;35(8):e1214-20 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/22868608.
  22. 22.0 22.1 22.2 Glencross J, Balasubramanian SP, Bacon J, Robinson MH, Reed MW. An audit of the management of soft tissue sarcoma within a health region in the UK. Eur J Surg Oncol 2003 Oct;29(8):670-5 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/14511616.
  23. 23.0 23.1 23.2 Pérez Romasanta LA, Montero Luis A, Verges Capdevila R, Mariño Cotelo A, Rico Pérez JM, SEOR Sarcoma Group. Centralised treatment of soft tissue sarcomas in adults. Clin Transl Oncol 2008 Feb;10(2):102-10 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/18258509.
  24. 24.0 24.1 Collin T, Blackburn AV, Milner RH, Gerrand C, Ragbir M. Sarcomas in the groin and inguinal canal--often missed and difficult to manage. Ann R Coll Surg Engl 2010 May;92(4):326-9 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20501018.
  25. 25.0 25.1 Marré D, Buendía J, Hontanilla B. Complications following reconstruction of soft-tissue sarcoma: importance of early participation of the plastic surgeon. Ann Plast Surg 2012 Jul;69(1):73-8 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21629048.
  26. 26.0 26.1 Zornig C, Peiper M, Schröder S. Re-excision of soft tissue sarcoma after inadequate initial operation. Br J Surg 1995 Feb;82(2):278-9 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/7749711.
  27. 27.0 27.1 Davis AM, Kandel RA, Wunder JS, Unger R, Meer J, O'Sullivan B, et al. The impact of residual disease on local recurrence in patients treated by initial unplanned resection for soft tissue sarcoma of the extremity. J Surg Oncol 1997 Oct;66(2):81-7 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/9354161.
  28. 28.0 28.1 Ueda T, Yoshikawa H, Mori S, Araki N, Myoui A, Kuratsu S, et al. Influence of local recurrence on the prognosis of soft-tissue sarcomas. J Bone Joint Surg Br 1997 Jul;79(4):553-7 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/9250737.
  29. 29.0 29.1 29.2 Bhangu AA, Beard JA, Grimer RJ. Should Soft Tissue Sarcomas be Treated at a Specialist Centre? Sarcoma 2004;8(1):1-6 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/18521386.
  30. 30.0 30.1 Merchant S, Cheifetz R, Knowling M, Khurshed F, McGahan C. Practice referral patterns and outcomes in patients with primary retroperitoneal sarcoma in British Columbia. Am J Surg 2012 Mar 12 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/22417850.
  31. 31.0 31.1 31.2 McCullough A, Scotland T, Dundas S, Boddie D. The impact of a managed clinical network on referral patterns of sarcoma patients in Grampian. Scott Med J 2014 Apr 1 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/24692232.
  32. Pisters PW, Leung DH, Woodruff J, Shi W, Brennan MF. Analysis of prognostic factors in 1,041 patients with localized soft tissue sarcomas of the extremities. J Clin Oncol 1996 May;14(5):1679-89 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/8622088.

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Appendices

Further resources