What is the ideal duration, frequency and modality of follow-up for BSTTs?

From Cancer Guidelines Wiki

Introduction

Bone and soft tissue tumours (BSTTs) are a rare and heterogenous group of tumours with variable patterns of recurrence and metastasis. These characteristics make it challenging to conduct large randomised studies required to generate evidence based guidelines for follow-up/surveillance.

Ideally, routine follow-up in sarcoma patients should be conducted in a cost-effective manner that has been scientifically proven to be beneficial. Unfortunately, however, guidelines for follow-up are typically based only on opinions of international experts as there have been no valid randomised trials comparing different follow-up schedules. The best guidelines available to date come from two European consensus statements on follow-up schedules.[1][2]

Consequently there is considerable variation in the intensity, duration and modality of follow-up in BSTTs.[3] Clinical trials are needed to identify optimal surveillance strategy that balances gains in survival, quality of life, costs and societal willingness to expend resources. Current guidelines world-wide do not specify where routine follow-up should take place or who should do it.

The major goals of follow-up for BSTTs are based on early identification of potentially curable recurrences, identification of treatment related morbidity (early and late) and patient reassurance.[4] Surveillance should be based on known prognostic factors, outcomes in individual subsets and patterns of recurrence. Follow-up should be both practical and relatively cost effective.

Approximately 30-40% of all patients with BSTTs develop local or distant recurrence.[5] The risk of recurrence is greatest in the first few years with approximately two out of three of recurrences developing within two years and 95% by five years and can be stratified into risk groups, based on the prognostic features of the primary tumour.[4] However, in some subgroups, such as retroperitoneal STS and myxoid liposarcoma, late recurrence and different patterns of recurrence are more common.[4]

There is no universally accepted stopping point for tumour surveillance.

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Undertaking follow-up for local recurrence

Most local recurrences will present within five years after initial therapy.[4] Risk of local recurrence can be stratified by primary tumour characteristics and margin status.[6] Local recurrence is isolated in two thirds of patients and there appears to be benefit in to aggressive treatment of isolated first and even multiply recurrent disease.[7]

More frequent follow-up in high-risk patients has been associated with improved survival in this group with recurrent BSST by providing greater opportunities for adequate re-operation or salvage therapy.[6]

Unlike bone sarcoma, most recurrences of soft tissue sarcoma are detected by clinical examination (by clinician or patient) rather than as a consequence of routine imaging.[5] However, the ability of individual patients to detect recurrence varies. Some can identify recurrences that are not discernible to doctors, while others can be unaware of a large tumour mass.

Routine anatomical imaging should be considered for patients with resected sarcoma, particularly in settings where the primary site is difficult to examine, for example the retroperitoneum or following complex/flap reconstructions. There is a paucity of evidence guiding frequency, duration of modality of imaging in follow-up for BSTTs. Choice of CT/MRI will be guided by site (e.g. extremity versus retroperitoneum).

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Follow-up intervals and tests for local recurrence

Intervals between routine visits are mostly arbitrary, but all suggested schedules have stipulated more frequent visits for patients with more advanced disease.

Six-monthly intervals for five years and yearly thereafter are probably appropriate for patients with fully resected low risk disease, and three-monthly or four-monthly intervals for five years and yearly thereafter for patients high risk disease. These intervals are based on the consistent observation that about 80% of recurrences develop in the first five years. Lifetime surveillance has been recommended by some because late recurrences have been recorded, particularly in some subtypes, such as myxoid sarcoma.[4]

There is general consensus that the most cost-effective component of a strategy resulting in the detection of the majority of recurrences is careful history taking and physical examination.

Choice of an imaging modality in surveillance will be guided by the site (e.g. extremity versus retroeritoneum) and nature of surgical resection and/or reconstruction (e.g. metallic implants). Ultrasound, CT, PET and MRI can be useful modalities, but the relative benefit and cost-efficacy of these modalities has not been evaluated.

Very few patients have metastases identified by the routine use of imaging techniques and blood tests. There are no randomised trials indicating that such tests are of value and in any case it would be difficult to prove that the few who survive did so merely because they underwent these tests.

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Metastatic recurrence

The lung is the most common site of metastasis in patients with BSTTs.[8] The majority of pulmonary metastastic disease will present within five years after initial therapy.[9]

Surgical metastastectomy is potentially curative for pulmonary sarcoma metastases, particularly for osteosarcoma and soft tissue sarcoma. Pulmonary metastasectomy offers three year overall survival between 30-42%.[10] However, there is no consensus on a pulmonary metastatic surveillance schedule.

CT chest is a superior imaging modality to conventional chest X-ray (CXR) in identification of pulmonary metastastes at a potentially resectable stage. Two year and four year survival rates after detection of pulmonary metastsasis were 20.1% and 0% in the plain radiograph (CXR) cohort versus 47.4% and 31.6% in the CT chest (p<0.05).[11]

Serial monitoring with chest CT could give rise to early detection of pulmonary metastases, chance for metastastasectomy and eventually survival advantage[11] athough interpretation of data would be thwarted by possible lead-time bias.

The recommendations given below are based on the best evidence currently available, but it is acknowledged that this is low-level evidence. Individual patients may prefer more frequent follow-up for reassurance, while others may prefer less frequent follow-up because of the anxiety provided by the follow-up visits or the time and expense associated with attendance for follow-up. However, the recommendations are a reasonable compromise which, reinforced by good patient education, should ensure that most sarcoma recurrences are detected promptly and potentially resectable metastatic progression is diagnosed early.

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Evidence summary and recommendations

Evidence summary Level References
Most extremity bone and soft tissue tumour recurrences will be detected by clinical examination rather than routine imaging.

The majority of local recurrences will occur within five years after resection.

Risk of local recurrence can be stratified by tumour site, grade and margin status.

More frequent follow-up in high-risk patients has been associated with improved survival in this group with recurrent BSTTs by providing greater opportunities for adequate re-operation or salvage therapy.

III-3, IV [6], [5]
Evidence-based recommendationQuestion mark transparent.png Grade
Regular clinical examination is part of routine surveillance for local recurrence.
D



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Where the primary site is difficult to examine, for example the retroperitoneum or following complex/flap reconstructions routine imaging may be appropriate.


Evidence summary Level References
Pulmonary surveillance offers potential survival advantage.

CT is superior to chest X-ray in identification of potentially resectable pulmonary sarcoma metastases

There is a lack of valid prospective studies of the efficacy of routine follow-up. No study has demonstrated an improvement in survival due to intense routine surveillance.

There may be some advantage in terms of patient reassurance and the detection of new metastastic progression.

III-3 [11]
Evidence-based recommendationQuestion mark transparent.png Grade
High risk patients in whom pulmonary metastasectomy would be considered, are advised to undergo three to six month CT chest until five years.
D



Practice pointQuestion mark transparent.png

Follow-up intervals recommended in current multinational guidelines are each three to four months in years one and two after diagnosis, six monthly in years three to four and annual thereafter.

Late metastases may occur >10 years after diagnosis and there is no universally accepted stopping point for tumour surveillance. By contrast, the incidence of late effects of treatment increases with time.

For patients enrolled in clinical trials, the above recommendations may vary in accordance with the follow-up protocols of these trials.


Practice pointQuestion mark transparent.png

For patients considered suitable for pulmonary metastasectomy, low dose protocol non- contrast CT chest is the modality of choice for pulmonary surveillance.

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Issues requiring more clinical research study

• What is the most cost effective imaging modality and surveillance interval for patients with resected sarcoma?

• What is the appropriate frequency of pulmonary surveillance for patients at differing risk of pulmonary metastases?

• What is the role of PET in long-term interval surveillance for resected sarcoma?

• What is the optimal duration of imaging surveillance in different risk groups?


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References

  1. Casali PG, Blay JY, ESMO/CONTICANET/EUROBONET Consensus Panel of experts. Soft tissue sarcomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2010 May;21 Suppl 5:v198-203 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20555081.
  2. Hogendoorn PC, Athanasou N, Bielack S, De Alava E, Dei Tos AP, Ferrari S, et al. Bone sarcomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2010 May;21 Suppl 5:v204-13 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20555083.
  3. Sakata K, Johnson FE, Beitler AL, Kraybill WG, Virgo KS. Extremity soft tissue sarcoma patient follow-up: tumor grade and size affect surveillance strategies after potentially curative surgery. Int J Oncol 2003 Jun;22(6):1335-43 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/12739002.
  4. 4.0 4.1 4.2 4.3 4.4 Patel SR, Zagars GK, Pisters PW. The follow-up of adult soft-tissue sarcomas. Semin Oncol 2003 Jun;30(3):413-6 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/12870143.
  5. 5.0 5.1 5.2 Whooley BP, Gibbs JF, Mooney MM, McGrath BE, Kraybill WG. Primary extremity sarcoma: what is the appropriate follow-up? Ann Surg Oncol 2000 Jan;7(1):9-14 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/10674442.
  6. 6.0 6.1 6.2 Chou YS, Liu CY, Chen WM, Chen TH, Chen PC, Wu HT, et al. Follow-up after primary treatment of soft tissue sarcoma of extremities: Impact of frequency of follow-up imaging on disease-specific survival. J Surg Oncol 2012 Feb 1 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/22297812.
  7. 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 1997 Feb;15(2):646-52 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/9053489.
  8. Fleming JB, Cantor SB, Varma DG, Holst D, Feig BW, Hunt KK, et al. Utility of chest computed tomography for staging in patients with T1 extremity soft tissue sarcomas. Cancer 2001 Aug 15;92(4):863-8 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/11550159.
  9. Pearlstone DB, Pisters PW, Bold RJ, Feig BW, Hunt KK, Yasko AW, et al. Patterns of recurrence in extremity liposarcoma: implications for staging and follow-up. Cancer 1999 Jan 1;85(1):85-92 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/9921978.
  10. Casson AG, Putnam JB, Natarajan G, Johnston DA, Mountain C, McMurtrey M, et al. Five-year survival after pulmonary metastasectomy for adult soft tissue sarcoma. Cancer 1992 Feb 1;69(3):662-8 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/1730117.
  11. 11.0 11.1 11.2 Cho HS, Park IH, Jeong WJ, Han I, Kim HS. Prognostic value of computed tomography for monitoring pulmonary metastases in soft tissue sarcoma patients after surgical management: a retrospective cohort study. Ann Surg Oncol 2011 Nov;18(12):3392-8 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21537873.

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Appendices

Further resources