8. Rehabilitation and aftercare – Soft Tissue Sarcoma
8.1 Follow-up in localized and metastatic stage
The follow-up plan for soft tissue sarcoma patients shall be determined by or in coordination with a certified sarcoma center or associated cooperation partner*.
* For specific subgroups such as DFSP/angiosarcoma/Kaposi's sarcoma, reference shall be made to the guidelines of the professional societies.
- Consensus
- Consent
Background
This strong recommendation for the follow-up of soft tissue sarcoma patients resulted from the review of the criteria of the Evidence to Decision (EtD) frameworks. The outcome of the review justifies the level of recommendation and sets out the balance of benefits and harms. The required decision making is structured and transparent.
Soft tissue sarcomas are rare diseases. The expertise to follow up patients is available at a certified sarcoma center. Sarcoma center certification has only been in place since 2018, so evidence in this area is not yet available and is the content of current research.
The benefit of follow-up per se and follow-up at or in coordination with the certified sarcoma center is for early detection of recurrence or metastases. Professional expertise is very high in all diagnostic and therapeutic areas.
Reactions from patients from Das Lebenshaus (now the German Sarcoma Foundation) show that they feel better off at a center. An uncontrolled follow-up close to home, especially if the sarcoma center is far away, leads to uncertainty for patients with such a rare disease.
The resource requirements are the same as for risk-adapted follow-up of other cancers. A long journey is accepted by the patients. It is cost-efficient, since imaging is evaluated on-site and, if necessary, further diagnostic/therapeutic measures can be agreed immediately in a personal discussion with the patient. Travel costs have a limited impact. Incorrect evaluation of radiological or clinical findings can lead to misjudgments, delays in therapy, or require diagnostic/therapeutic measures which would otherwise be unnecessary. This leads to a higher consumption of resources.
Therefore, the follow-up plan for soft tissue sarcoma patients should be determined by or in coordination with a certified sarcoma center or associated cooperation partner.
8.1.1 Timing of the follow-up examinations
During follow-up after local therapy of highly malignant sarcomas, frequent control intervals (3 months) should be observed in the first 2 years after completion of therapy, since the probability of recurrence or metastasis is highest during this period.
- Consensus
- Strong consensus
Background
The evidence base regarding the implementation and design of follow-up for soft tissue sarcomas is insufficient. Accordingly, there is a significant heterogeneity between the follow-up strategies in clinical practice [564], [565]. Regular follow-up examinations following a successful tumor resection serve to detect local recurrences and/or metastases at an early stage in order to deliver necessary therapy to improve the overall prognosis [566], [567], [568].
Tumor entity, tumor size and localization, and histologic grading have a major impact on the local recurrence rate and metastatic behavior of soft tissue sarcomas, especially when combined. In this regard, histologic grading is of major importance in the vast majority of different entities [112], [134], [135], [566], [569]. This should be taken into account when planning follow-up.
The wide diversity of tumor entities is problematic for establishing a general recommendation [566]. Local recurrences typically occur within the first two years after tumor resection, but in certain tumor entities (Atypical lipomatous tumor /G1 liposarcoma) it may occur even after >5 years. Retrospective analyses suggest a limitation of the follow-up period to 10 years, but late recurrences/metastases may also be observed after more than 15 years in individual entities [570], [571].
Adaptations are also required with regard to the body regions to be monitored. Thus, myxoid liposarcomas tend to osseous and soft tissue metastases. Accordingly, in addition to an MRI of the affected region, an MRI examination of the neighboring regions, especially in the lymphatic drainage area should be performed [572].
Besides a few retrospective studies, only one prospective randomized study is available. However, this study could not prove the non-inferiority of planned follow-up examinations at an interval of 6 months compared to 3 months in the first 2 years after surgical resection therapy [573].
Table 12: Well differentiated sarcomas
(low-grade according to FNCLCC [113])
|
Year 1and 2 |
Year 3 to 5 |
From year 6 |
|
Interval: 3-6 months
Physical examination Imaging: Tumor region (kmMRI) Lung (low-dose CT) |
Interval: 6 months
Physical examination Imaging: Tumor region (kmMRI) Lung (low-dose CT) |
Interval: 12 months
Physical examination Imaging: Tumor region (kmMRI) Lung (low-dose CT) |
Table 13: Poorly differentiated sarcomas
(high grade according to FNCLCC [113])
|
Year 1 and 2 |
Year 3 to 5 |
From year 6 |
|
Interval: 3 months
Physical examination Imaging: Tumor region (kmMRI) Lung (low-dose CT) |
Interval: 6 months
Physical examination Imaging: Tumor region (kmMRI) Lung (low-dose CT) |
Interval: 12 months
Physical examination Imaging: Tumor region (kmMRI) Lung (low-dose CT) |
8.1.1.1 Retroperitoneal sarcomas
For G2 and G3 retroperitoneal soft tissue sarcomas, follow-up should be every 3 months for the first 2 years as for other highly malignant sarcomas. For G1 liposarcomas, intervals of 6 months are recommended because of the more favorable tumor biology.
- Consensus
- Strong consensus
In cases of retroperitoneal sarcoma, anticipated artifacts in the study area, or if there are reasons not to undergo MRI, contrast-enhanced CT should be performed.
- Consensus
- Strong consensus
Background
Follow-up of retroperitoneal sarcomas should follow the plan of high-grade sarcomas regardless of their grading [247]. In retroperitoneal sarcomas, the main focus is on the detection of locoregional recurrence and, in dedifferentiated liposarcomas, on the detection of a de novo second tumor. Because of the anatomic changes that occur as a result of multivisceral resection, abdominal MRI is the best possible technique for delineating anatomic structures. If artifacts are expected in the study area (e.g., after prosthesis implantation), or if there are reasons not to perform MRI, contrast-enhanced computed tomography should be performed [574], [575]. A condition after nephrectomy in the context of the preceding tumor resection can become problematic here. If CT can be performed despite this, oral contrast is indicated not with i.v.
For the detection of local recurrences after surgical therapy of RPS, the patient's self-perception plays a lesser role. However, descriptions of newly occurring disturbances in sensitivity, e.g. in the femoral nerve region, could raise suspicion.
8.1.2 Clinical examination and instrumental diagnostics
8.1.2.1 Medical history and physical examination
For the detection of local recurrences after surgical therapy of extremity sarcomas, self-awareness of the patients plays a special role. Patients with these tumor localizations should therefore be advised to perform self-examination and taught what to look for.
- Consensus
- Strong consensus
Background
In addition to the assessment of the general condition, the detailed questioning of the patient’s memory should particularly look for signs of recurrent tumor growth or indications of metastases. Descriptions of nonspecific musculoskeletal complaints, or in special cases circumscribed disturbances of motor function or sensibility, may raise suspicion [567], [568].
Local physical examination in the area of the original primary tumor should identify newly occurring space-occupying processes. Here, attention must also be paid to possible consequences of radiation therapy. Also, the draining lymphatic nodes should be examined for abnormalities.
Retrospective studies showed that the vast majority of tumor recurrences were first detected by the patient themself, between scheduled follow-up appointments, as a newly occurring mass [566], [573].
8.1.2.2 Imaging examinations
In the follow-up of soft tissue sarcomas of the extremities, contrast-enhanced magnetic resonance imaging is the method of choice.
- Consensus
- Strong consensus
In the detection of pulmonary metastases after primary therapy of sarcomas, clinical symptoms do not play a relevant role. Therefore, patients at significant risk for pulmonary metastasis shall undergo image-based follow-up (CT or chest X-ray).
- Consensus
- Consent
Background
In the diagnosis of soft tissue sarcomas of the extremities, contrast-enhanced magnetic resonance imaging is considered the method of choice [574], [575] and in follow-up imaging is valid in differentiating postoperative conditions from tumor regrowth [568], [573]. MR tomographic imaging allows differentiation between scarring and tumor recurrence in follow-up and coarse assessment when the previous findings are known and therapies performed are included [576]. In nonmyxoid tumors, diffusion weighting can improve the detection of tumor recurrence [577].
Regular imaging of the lung, as the primary metastatic site of soft tissue sarcomas, is mandatory. There is no clear recommendation on the preference of CT examination over conventional X-ray radiography in two planes. However, if CT provides additional information, the higher radiation exposure must be put into perspective [573]. Various working groups were able to show in individual retrospective observations that conventional imaging is not inferior to CT diagnostics and can be evaluated as adequate considering the costs, the false-positive findings and also the radiation exposure in the follow-up [566], [568], [578], [579]. Also the only available prospective study on follow-up by Puri et al. from 2014 with 500 included patients could not prove an advantage of CT over conventional chest imaging [573]. With significantly reduced radiation exposure and yet comprehensive image information, low-dose CT of the thorax offers the preferred alternative to conventional X-ray examination in the overall context.
8.1.2.3 Laboratory diagnostics
Standardized laboratory chemistry testing during follow-up shall not be performed.
- Consensus
- Strong consensus
If chemotherapies have been used, laboratory chemistry tests should be performed during follow-up (see S3 Guideline Supportive Therapy in Oncology Patients, Chapters 3+4).
- Consensus
- Strong consensus
Background
However, in the case of neoadjuvant or adjuvant chemotherapies, extended follow-up should look for signs of organ toxicity and consequent dysfunction (see also S3 guideline Supportive Therapy in Oncology Patients, https://www.leitlinienprogramm-onkologie.de/leitlinien/supportive-therapie/ [538].
8.1.3 Follow-up in the metastasized stage
In the metastatic, or locally recurrent stage, after R0/1 resection, the follow-up strategy should be the same as that in the localized stage.
- Consensus
- Strong consensus
Follow-up of patients with metastatic soft tissue sarcomas who cannot be treated with curative therapy should be based on the detection of tumor progression and the indication for further local or drug therapies or supportive therapy (see also section 9.3).
- Consensus
- Strong consensus
Background
In this context, the resection of the metastasis/recurrence should be compared with the initial diagnosis or the first complete resection of the primary tumor when planning the examination intervals.
Patients should be included in palliative care with the goal of symptom control according to the extended S3 guideline „Palliative care for patients with non-curable cancer“, version 2.2, 2020, AWMF registry number: 128/001OL, https://www.leitlinienprogramm-onkologie.de/leitlinien/palliativmedizin [580]).
Regarding supportive therapy, reference is made to the S3 guidelines „Supportive therapy in oncology patients“, version 1.3, 2020, AWMF Registry Number: 032/054OL.
8.2 Medical rehabilitation
Medical rehabilitation serves the treatment of disease and therapy-related secondary disorders in order to regain an active lifestyle and professional, private and social participation. In addition to targeted multimodal approaches for individual sequelae, the aim is to improve the patients' quality of life, their ability to cope with the disease and the acceptance of possible permanent limitations is to be supported.
After completion of primary therapy, follow-up rehabilitation shall be offered to all patients capable of rehabilitation.
- Consensus
- Consent
Medical rehabilitation should be performed in an oncological rehabilitation facility, taking into account functional disorder with any orthopedic focus (e.g., after resection of an extremity sarcoma).
- Consensus
- Consent
If symptoms persist, patients should be informed about the possibility of further rehabilitation measures.
- Consensus
- Strong consensus
Background
Oncological patients are entitled to medical rehabilitation services as stipulated in Book IX of the Social Code (SGB IX). These measures aim to promote the patients' self-determination and their equal participation in life and society, to avoid disadvantages or to counteract them [581].
The need for rehabilitation services always exists when there is a tumor- or therapy-related functional restriction that is a permanent impairment in daily life. The patient is considered fit for rehabilitation if his or her physical and mental condition (e.g., ability to cope with stress, motivation or motivability) is sufficient for participation in a rehabilitation service.
Rehabilitation services can be provided as follow-up rehabilitation directly after completion of inpatient or outpatient primary treatment. In this case, follow-up rehabilitation is initiated by the last treating physician or social service of the last treating clinic; follow-up rehabilitation is carried out in special rehabilitation facilities suitable for this purpose [582]. If serious functional disorders persist, further rehabilitation services can be claimed. For this purpose, an application must be submitted to the responsible cost unit.
The cost units for oncological rehabilitation are, in addition to the German Pension Insurance, also health insurance funds, employers' liability insurance associations or other social insurance providers. The legal basis for this can be found in the SGB V in the case of the GKV or in the SGB VI in the case of the DRV.
Requirements for the structural, process and outcome quality of oncological rehabilitation have been formulated by the Federal Working Group for Rehabilitation (BAR) and the German Pension Insurance (DRV) and are regularly monitored in an elaborate external quality management process [583], [584], [585].
The requirement profiles for rehabilitation facilities are sensibly based on the more common cancers (breast, colon, prostate, lung cancer). Patients with soft tissue sarcomas are typically not addressed with specific rehabilitation offers. In order to address the special sarcoma problems, it may be necessary to deviate from the usual routines of assigning patients to rehabilitation clinics.
Due to the very complex and variable pattern of limitations in patients with adult soft tissue sarcoma, an interdisciplinary and multimodal approach to rehabilitation is essential. For example, in cases of specific orthopedic dysfunction which may be an outcome for patients with extremity sarcoma, the selection of a suitable oncology clinic with an additional orthopedic focus may be appropriate. A study of 728 patients with extremity sarcoma showed that early functional rehabilitation resulted in significantly improved oncologic outcome (OR 0.5, CI 0.3-0.9) [586].
According to current framework agreements, medical rehabilitation must always be oriented to a comprehensive bio-psychosocial model of disease, which is based on the International Classification of Functioning, Disability and Health (ICF) of the World Health Organization (WHO) [587]. In this model, a patient is viewed as an individual, recognising contextual factors, and the disease, as well as its consequences. These are understood together with mutually influencing somatic, psychological and social factors.
In addition to the individual rehabilitation goals to be formulated based on the criteria of the ICF, the objectives of oncological rehabilitation in patients with adult soft tissue sarcoma generally include the following:
- Diagnosis and treatment of disease and therapy-related sequelae.
- Preservation or restoration of physical and mental capacity
- Preservation or re-enablement of participation in normal social life and,
- if the patient is still at work, maintenance or restoration of earning capacity.
Patients with adult soft tissue sarcoma have limitations, depending on tumor location and type of primary intervention, predominantly due to musculo-skeletal problems. For example, patients with extremity sarcoma have significantly reduced physical activity compared with their age cohort, even in the long term, as shown in a systematic review by Kwong et. al. [588]. Authors of a data analysis of the Childhood Cancer Survivor Study (CCSS) [589] concluded that there is a need for rehabilitation services and, in particular, exercise-based therapy services.
A review by Gerrand and Furtado shows that a relevant proportion of sarcoma patients also suffer from various other sequelae in addition to musculoskeletal limitations: 28 % of patients report severe tumor-associated exhaustion (fatigue), almost all patients report pain (9.5 % of it severe), about one third suffers from lymphedema; a large proportion of up to 77 % of patients show long-term psychosocial problems such as depression, social withdrawal or sexual dysfunction, which also results in a need for rehabilitation. The authors conclude that ICF-based multidisciplinary rehabilitation enables patients to achieve normalization of physical and psychosocial function, as well as participation, and should therefore be started early [590].
Medical rehabilitation in patients with adult soft tissue sarcoma
Patients with soft tissue sarcoma should be offered early systematic exercise therapy.
- Recommendation grade
- B: Empfehlung für oder gegen eine Maßnahme - verwendete Ausdrucksweise = sollte/sollte nicht
- Level of evidence
- ⊕⊝⊝⊝
Overall survival (median follow-up: 140 months SRAS, 40 months ERAS).
⊕⊝⊝⊝Risk of local recurrence (median follow-up: 140 months SRAS, 40 months ERAS).
⊕⊝⊝⊝Overall morbidity (median follow-up: 140 months SRAS, 40 months ERAS).
- Consensus
- Strong consensus
Background
A comparative study by Michot et al. demonstrated the benefit of early systematic exercise therapy and rehabilitation treatment on wound healing, number of hospital days, and functional outcome for patients with adult soft tissue sarcoma [591].
Unfortunately, further systematic evidence on the effect of rehabilitation treatment is not available for this small patient population.
However, a general literature search on oncological rehabilitation, or on individual therapeutic modalities used in rehabilitation, such as exercise and sports therapy, shows overarching positive effects, or positive effects proven for other oncological entities, from which a benefit of rehabilitation can also be at least inferred for patients with soft tissue sarcoma. Thus, it has been shown that oncological patients benefit from physical training at every stage of therapy in terms of quality of life, function, and activity, and sequelae such as tumor-related fatigue symptoms could be improved [592], [593], [594]. For patients with osteosarcoma, it has been shown that their subjective quality of life depends less on the surgical approach and more on the functional outcome achieved [595] and that functional improvements can be achieved by rehabilitation treatment [596], [597], [598].
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