- 1 What is the ideal duration, frequency and modality of follow-up for BSTTs?
- 2 Evidence summary and recommendations
- 3 Issues requiring more clinical research study
- 4 References
- 5 Appendices
- 6 Further resources
What is the ideal duration, frequency and modality of follow-up for BSTTs?
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.
Consequently there is considerable variation in the intensity, duration and modality of follow-up in BSTTs. 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. 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. 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. However, in some subgroups, such as retroperitoneal STS and myxoid liposarcoma, late recurrence and different patterns of recurrence are more common.
There is no universally accepted stopping point for tumour surveillance.
Undertaking follow-up for local recurrence
Most local recurrences will present within five years after initial therapy. Risk of local recurrence can be stratified by primary tumour characteristics and margin status. 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.
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.
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. 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).
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.
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.
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%. 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).
Serial monitoring with chest CT could give rise to early detection of pulmonary metastases, chance for metastastasectomy and eventually survival advantage 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.
Evidence summary and recommendations
| 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||, |
|Regular clinical examination is part of routine surveillance for local recurrence.||D|
Where the primary site is difficult to examine, for example the retroperitoneum or following complex/flap reconstructions routine imaging may be appropriate.
| 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.
|High risk patients in whom pulmonary metastasectomy would be considered, are advised to undergo three to six month CT chest until five years.||D|
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.
For patients considered suitable for pulmonary metastasectomy, low dose protocol non- contrast CT chest is the modality of choice for pulmonary surveillance.
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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