What is the impact of delay in referral to a specialist centre in BSTTs?

From Cancer Guidelines Wiki

Introduction

Delay in instituting definitive management of sarcoma can arise through a variety of mechanisms, including patient delay in presentation (time between onset of symptoms and first seeking medical advice), and medical delay (in referring the patient to a specialist centre). Medical referral delay may arise through failure to recognise the problem e.g. thinking that a soft tissue mass is a harmless lipoma, delays in obtaining complicated imaging or other assessments e.g. waiting for a CT scan or biopsy, or referral to a non-specialist unit or surgeon who lacks specific expertise in sarcoma, who may then also delay referring the patient on to a specialist centre, or fail to do so at all. Before reaching a specialist unit, the patient may have been falsely reassured and had no intervention at all, or have had inappropriate or inadequate investigations and/or surgery prior to definitive management, and in some cases will only finally reach a specialist unit (if at all) after local and/or distant recurrence.[1] Whatever the cause of delay, there is evidence that delayed referral to a specialist centre (or failure to refer at all and managing the patient in a non-specialist unit) impacts on patient outcomes.

Definition of delay

There is no clear consensus as to what constitutes a “delay” in referral or, by extrapolation, what time interval is acceptable. Definitions of delay range from greater than three weeks[2] to “more than a month”[3] to three months or more,[4] but it is clear that many patients have symptoms for some months or even years before reaching a sarcoma unit. Patient-related delay in presentation can be as long as twenty-six months,[3] and medical delay in referral even longer: ten years in one extreme example,[3] but more often from a few months [5] to around a year.[3][4]

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Impact of referral delay on subsequent management

The most obvious result of a delay in definitive management is tumour progression (either growth of the primary or, potentially, the development of distant metastases). But inexpert attempts at management e.g. delaying specialist referral while waiting for imaging or biopsies, may also impact on subsequent management. Many studies[3][4][5] [6] have highlighted the frustration felt by specialist centres when patients are referred after undergoing inappropriate or inadequate “work-up”, which then needs to be repeated before definitive treatment can be instituted, resulting in further delay. In one study of 100 consecutive patients referred to a specialist unit,[3] 63 had undergone “complex” imaging prior to referral, and in 56 of these, further imaging was performed to obtain information that was considered necessary to plan treatment.

Even more concerning are the cases where inappropriate or inadequate biopsy, or incomplete excision, have been undertaken prior to referral. Apart from the delay incurred in repeating a previously non-diagnostic biopsy, in many cases a poorly planned biopsy may impact on subsequent management such as requiring more radical surgery, compromising flaps or necessitating adjunctive chemo- or radiotherapy which might otherwise have been avoided. For example, in the study by Ashwood et al.[3] 34 of the 100 patients had undergone biopsy or surgery prior to referral, which complicated further treatment in 16 of these. Two studies by Mankin et al.[7][8] more than a decade apart showed strikingly similar results: in the first study[7] 34% of patients undergoing biopsy prior to specialist referral had “non-representative or technically poor” biopsies. The subsequent management plan was altered in 18.2% because of biopsy-related problems in the first study and 19.3% in the second.[8]

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Impact of referral delay on patient outcomes

Some patients are not referred to a specialist unit at all but are managed in a non-specialist centre, and (at least in the UK) these patients have been found to have lower survival rates.[9] But even a delay in referral can impact on the patient’s clinical course: Clark & Thomas [4] found a referral delay of greater than three months to be “likely to have had a detrimental effect” on treatment options and outcomes in one fifth of patients and other studies have shown a correlation between the duration of symptoms prior to treatment and disease relapse, distant metastases and survival[10][11] and with chemoresponse.[2] Conversely, Han et al.[12] found no significant difference in disease-free survival or local recurrence according to time to definitive surgery, but positive surgical margins and greater tumour size were predictive of local control.

In the two studies by Mankin et al. referred to above,[7] [8] prognosis or outcome was considered to have been affected by pre-referral biopsy in 8.5% of patients in the first study[7] and 10.1% in the second.[8] These effects ranged from more radical surgery resulting in loss of function and long-term disability to increased rates of local recurrence and mortality. And patients who were referred after undergoing initial surgery in nonspecialist units underwent a greater number of operations and more often experienced local recurrence, than those who were referred directly to a specialist unit.[13]

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Evidence summary and recommendations

Evidence summary Level References
Delays in referral to specialist sarcoma units are common and sometimes lengthy, often have adverse consequences for subsequent patient management, and may well impact on patient outcomes. IV [1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13]
Evidence-based recommendationQuestion mark transparent.png Grade
Immediate referral to a specialist sarcoma unit to be sought when a tumour of bone or soft tissue (other than simple lipoma) is suspected.
D



Practice pointQuestion mark transparent.png

In practice, any mass lesion greater than 5cm in size, and lesions deep to or attached to deep fascia, should be considered a sarcoma until proven otherwise.


Practice pointQuestion mark transparent.png

Refer to a specialist sarcoma unit.

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Issues requiring more clinical research study

A gap in the evidence has been identified:

  • What are the barriers to diagnosis and treatment of sarcoma and their impact on patient outcomes?

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References

  1. 1.0 1.1 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.
  2. 2.0 2.1 2.2 Bielack SS, Kempf-Bielack B, Delling G, Exner GU, Flege S, Helmke K, et al. Prognostic factors in high-grade osteosarcoma of the extremities or trunk: an analysis of 1,702 patients treated on neoadjuvant cooperative osteosarcoma study group protocols. J Clin Oncol 2002 Feb 1;20(3):776-90 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/11821461.
  3. 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 Ashwood N, Witt JD, Hallam PJ, Cobb JP. Analysis of the referral pattern to a supraregional bone and soft tissue tumour service. Ann R Coll Surg Engl 2003 Jul;85(4):272-6 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/12855033.
  4. 4.0 4.1 4.2 4.3 4.4 Clark MA, Thomas JM. Delay in referral to a specialist soft-tissue sarcoma unit. Eur J Surg Oncol 2005 May;31(4):443-8 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/15837054.
  5. 5.0 5.1 5.2 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.
  6. 6.0 6.1 Widhe B, Bauer HC. Diagnostic difficulties and delays with chest wall chondrosarcoma: a Swedish population based Scandinavian Sarcoma Group study of 106 patients. Acta Oncol 2011 Apr;50(3):435-40 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20545566.
  7. 7.0 7.1 7.2 7.3 7.4 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.
  8. 8.0 8.1 8.2 8.3 8.4 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.
  9. 9.0 9.1 Stiller CA, Passmore SJ, Kroll ME, Brownbill PA, Wallis JC, Craft AW. Patterns of care and survival for patients aged under 40 years with bone sarcoma in Britain, 1980-1994. Br J Cancer 2006 Jan 16;94(1):22-9 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/16317433.
  10. 10.0 10.1 Goyal S, Roscoe J, Ryder WD, Gattamaneni HR, Eden TO. Symptom interval in young people with bone cancer. Eur J Cancer 2004 Oct;40(15):2280-6 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/15454254.
  11. 11.0 11.1 Yang JY, Cheng FW, Wong KC, Lee V, Leung WK, Shing MM, et al. Initial presentation and management of osteosarcoma, and its impact on disease outcome. Hong Kong Med J 2009 Dec;15(6):434-9 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/19966347.
  12. 12.0 12.1 Han I, Kang HG, Kang SC, Choi JR, Kim HS. Does delayed reexcision affect outcome after unplanned excision for soft tissue sarcoma? Clin Orthop Relat Res 2011 Mar;469(3):877-83 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21046299.
  13. 13.0 13.1 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.

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Appendices

Further resources