Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

INITIAL

identification of primary site pending

1st line – supportive care

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INITIAL
|
identification of primary site pending
1st line – 

supportive care

Supportive care should be initiated, ideally under the guidance of a palliative care physician or team.

Initial treatment strategies are aimed at controlling symptoms attributable to the underlying process, such as pain or local obstruction, and the focus should be on palliation of symptoms.

Bone pain: typically requires treatment with a non-steroidal anti-inflammatory drug (NSAID), an opioid analgesic, or a corticosteroid, or a suitable combination of these agents. Zoledronic acid (a bisphosphonate) or denosumab can be given for pain due to bone metastases and to decrease risk of skeletal-related events such as fractures. Palliative radiation can also be considered.

Neuropathic pain: may respond to anticonvulsant therapy (e.g., gabapentin) or antidepressant therapy (e.g., duloxetine).

Local pain: can be treated with regional nerve blocks or radiotherapy.

Obstructive symptoms: are related to tumour mass or localised inflammation, and are common (e.g., bowel, biliary, and bronchial obstruction). Obstructive symptoms should be aggressively managed, using a multi-disciplinary approach, with interventional radiology, endoscopic or surgical intervention, radiotherapy, and pharmacotherapy, as appropriate.

Other symptoms requiring attention include fatigue, depression, anorexia, nausea, and delirium.

Plus – commence chemotherapy

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INITIAL
|
identification of primary site pending
|
investigations complete and good performance status
Plus – 

commence chemotherapy

Treatment recommended for ALL patients in selected patient group

Chemotherapy has been the cornerstone of treatment of adenocarcinoma of unknown primary site (ACUP), and is used empirically with palliative intent in patients with an unfavourable subtype.[2][3]​​

Many chemotherapeutic regimens have been assessed, but systematic reviews and meta-analyses have failed to demonstrate superiority of one regimen over another.​[34][35][36]​​ One meta-analysis reported a tendency towards improved survival with regimens containing platinum agents or taxanes.[36]

The performance status of the patient is a critical treatment determinant. The Eastern Cooperative Oncology Group (ECOG) scale, ranging from 0 (fully active) to 5 (dead), is commonly used to assess performance. See Diagnostic criteria.

The majority of patients with ACUP are older adults, with some functional impairment related to the advanced disease.

National Comprehensive Cancer Network (NCCN) guidelines recommend consideration of systemic therapy for patients who are: symptomatic with performance status of 1-2; or asymptomatic with aggressive cancer and performance status 0.[2]

ACUTE

unfavourable subtype: multiple metastases and/or without a likely primary site

1st line – chemotherapy

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ACUTE
|
unfavourable subtype: multiple metastases and/or without a likely primary site
1st line – 

chemotherapy

For patients with adenocarcinoma of unknown primary site (ACUP) in whom a favourable clinico-pathological subtype is not identified, the recommended initial treatment is empiric chemotherapy.[2][3]​​

Standard empirical chemotherapy for patients with ACUP is a doublet regimen comprising a platinum agent combined with either a taxane (paclitaxel or docetaxel) or gemcitabine.[2][3] Responses are not durable (median survival approximately 12 months among patients with good performance status).[37][38]

There is no agreement on appropriate second-line therapy for patients previously treated with platinum-containing regimens; no single agent or combination has proven beneficial (response rate or median survival). Decisions about second-line therapy are based on oncologist preference, or on other patient characteristics that may prevent the use of certain cytotoxic drug classes.

See local specialist protocol for dosing guidelines.

Primary options

carboplatin

or

cisplatin

-- AND --

gemcitabine

OR

carboplatin

or

cisplatin

-- AND --

docetaxel

or

paclitaxel

Plus – supportive care

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ACUTE
|
unfavourable subtype: multiple metastases and/or without a likely primary site
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

Supportive care should be initiated, ideally under the guidance of a palliative care physician or team.

Focus should be on palliation of symptoms.

Bone pain: typically requires treatment with a non-steroidal anti-inflammatory drug (NSAID), an opioid analgesic, or a corticosteroid, or a suitable combination of these agents. Zoledronic acid (a bisphosphonate) or denosumab can be given for pain due to bone metastases and to decrease risk of skeletal-related events such as fractures. Palliative radiation can also be considered.

Neuropathic pain: may respond to anticonvulsant therapy (e.g., gabapentin) or antidepressant therapy (e.g., duloxetine).

Local pain: can be treated with regional nerve blocks or radiotherapy.

Obstructive symptoms: are related to tumour mass or localised inflammation, and are common (e.g., bowel, biliary, and bronchial obstruction). Obstructive symptoms should be aggressively managed, using a multi-disciplinary approach, with interventional radiology, endoscopic or surgical intervention, radiotherapy, and pharmacotherapy, as appropriate.

Other symptoms requiring attention include fatigue, depression, anorexia, nausea, and delirium.

favourable subtype: women with isolated axillary lymphadenopathy (likely breast primary)

1st line – primary breast cancer management protocol

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ACUTE
|
favourable subtype: women with isolated axillary lymphadenopathy (likely breast primary)
1st line – 

primary breast cancer management protocol

Female patients presenting with isolated axillary adenopathy and documented adenocarcinoma should undergo mammography for suspected breast cancer.[2]

Contrast-enhanced breast MRI and/or breast ultrasound is indicated if mammography is not diagnostic but there is histopathological evidence for breast cancer.[2]

Retrospective studies indicate that breast MRI can help to identify the primary cancer in approximately two-thirds of patients with negative clinical examination and negative mammography.[39]​

Evaluation of immunohistochemical markers of breast cancer (e.g., GATA3; oestrogen receptor/progesterone receptor [ER/PR]) is recommended in women with isolated axillary lymphadenopathy.[2]

Tumours that are ER-/PR-positive may be treated with hormonal therapy.

Patients with likely breast primary should be managed according to primary breast cancer protocols.​[2][3]​​ See Primary invasive breast cancer.

Plus – supportive care

Back
ACUTE
|
favourable subtype: women with isolated axillary lymphadenopathy (likely breast primary)
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

Supportive care should be initiated, ideally under the guidance of a palliative care physician or team.

Focus should be on palliation of symptoms.

Bone pain: typically requires treatment with a non-steroidal anti-inflammatory drug (NSAID), an opioid analgesic, or a corticosteroid, or a suitable combination of these agents. Zoledronic acid (a bisphosphonate) or denosumab can be given for pain due to bone metastases and to decrease risk of skeletal-related events such as fractures. Palliative radiation can also be considered.

Neuropathic pain: may respond to anticonvulsant therapy (e.g., gabapentin) or antidepressant therapy (e.g., duloxetine).

Local pain: can be treated with regional nerve blocks or radiotherapy.

Obstructive symptoms: are related to tumour mass or localised inflammation, and are common (e.g., bowel, biliary, and bronchial obstruction). Obstructive symptoms should be aggressively managed, using a multi-disciplinary approach, with interventional radiology, endoscopic or surgical intervention, radiotherapy, and pharmacotherapy, as appropriate.

Other symptoms requiring attention include fatigue, depression, anorexia, nausea, and delirium.

favourable subtype: women with peritoneal carcinomatosis of a serous papillary adenocarcinoma (likely ovarian primary)

1st line – ovarian cancer management protocol

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ACUTE
|
favourable subtype: women with peritoneal carcinomatosis of a serous papillary adenocarcinoma (likely ovarian primary)
1st line – 

ovarian cancer management protocol

Histologically analogous to stage III ovarian cancer.

BRCA1/2 germline mutations may be present and CA 125 is typically elevated, consistent with an ovarian cancer profile.

First-line therapy is similar to that for advanced-stage ovarian cancer, which includes optimal surgical debulking and adjuvant platinum-based chemotherapy, generally a taxane/platinum doublet.[3]​​

There is some evidence, although not consistent, to support the use of intraperitoneal chemotherapy for advanced-stage ovarian cancer; its potential role in the management of papillary adenocarcinoma of the peritoneal cavity has not yet been evaluated.[40][41][42]

Patients with ovarian-like cancer of unknown primary (CUP) are treated per ovarian cancer guidelines.​[2][3]​​​ See Ovarian cancer.

Plus – supportive care

Back
ACUTE
|
favourable subtype: women with peritoneal carcinomatosis of a serous papillary adenocarcinoma (likely ovarian primary)
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

Supportive care should be initiated, ideally under the guidance of a palliative care physician or team.

Focus should be on palliation of symptoms.

Bone pain: typically requires treatment with a non-steroidal anti-inflammatory drug (NSAID), an opioid analgesic, or a corticosteroid, or a suitable combination of these agents. Zoledronic acid (a bisphosphonate) or denosumab can be given for pain due to bone metastases and to decrease risk of skeletal-related events such as fractures. Palliative radiation can also be considered.

Neuropathic pain: may respond to anticonvulsant therapy (e.g., gabapentin) or antidepressant therapy (e.g., duloxetine).

Local pain: can be treated with regional nerve blocks or radiotherapy.

Obstructive symptoms: are related to tumour mass or localised inflammation, and are common (e.g., bowel, biliary, and bronchial obstruction). Obstructive symptoms should be aggressively managed, using a multi-disciplinary approach, with interventional radiology, endoscopic or surgical intervention, radiotherapy, and pharmacotherapy, as appropriate.

Other symptoms requiring attention include fatigue, depression, anorexia, nausea, and delirium.

favourable subtype: poorly differentiated carcinoma with neuroendocrine features (likely small cell lung cancer primary)

1st line – small cell lung cancer management protocol

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ACUTE
|
favourable subtype: poorly differentiated carcinoma with neuroendocrine features (likely small cell lung cancer primary)
1st line – 

small cell lung cancer management protocol

A significant minority of poorly differentiated or undifferentiated carcinomas have neuroendocrine features identified by histological assessment. Favourable neuroendocrine carcinoma subtypes are not considered in European guidelines because an elusive primary cancer is a common finding.[3]

Combination chemotherapy with paclitaxel, carboplatin, and etoposide was associated with a major response rate of 53% (median survival 14.5 months; 2- and 3-year survival rates of 33% and 24%, respectively) in one phase 2 clinical trial of treatment-naive patients with metastatic poorly differentiated neuroendocrine carcinoma.[43]​ In a subsequent phase 2 study, irinotecan and cisplatin was not inferior to etoposide and cisplatin in patients with poorly differentiated gastroenteropancreatic neuroendocrine carcinoma.[44]​ Enrolment to the study was terminated early (n=66 patients) because initial analyses reported similar response rates.[44]

Poorly differentiated neuroendocrine tumours are treated per small cell lung cancer guidelines.[2][45]​ See Small cell lung cancer.

Plus – supportive care

Back
ACUTE
|
favourable subtype: poorly differentiated carcinoma with neuroendocrine features (likely small cell lung cancer primary)
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

Supportive care should be initiated, ideally under the guidance of a palliative care physician or team.

Focus should be on palliation of symptoms.

Bone pain: typically requires treatment with a non-steroidal anti-inflammatory drug (NSAID), an opioid analgesic, or a corticosteroid, or a suitable combination of these agents. Zoledronic acid (a bisphosphonate) or denosumab can be given for pain due to bone metastases and to decrease risk of skeletal-related events such as fractures. Palliative radiation can also be considered.

Neuropathic pain: may respond to anticonvulsant therapy (e.g., gabapentin) or antidepressant therapy (e.g., duloxetine).

Local pain: can be treated with regional nerve blocks or radiotherapy.

Obstructive symptoms: are related to tumour mass or localised inflammation, and are common (e.g., bowel, biliary, and bronchial obstruction). Obstructive symptoms should be aggressively managed, using a multi-disciplinary approach, with interventional radiology, endoscopic or surgical intervention, radiotherapy, and pharmacotherapy, as appropriate.

Other symptoms requiring attention include fatigue, depression, anorexia, nausea, and delirium.

favourable subtype: well-differentiated neuroendocrine tumours (likely neuroendocrine primary)

1st line – neuroendocrine tumour management protocols

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ACUTE
|
favourable subtype: well-differentiated neuroendocrine tumours (likely neuroendocrine primary)
1st line – 

neuroendocrine tumour management protocols

Neuroendocrine tumours include islet cell tumours, carcinoid tumours, and gastrinomas, among others. Favourable neuroendocrine carcinoma subtypes are not considered in European guidelines because an elusive primary cancer is a common finding.[3]

If feasible, surgical debulking or chemoembolisation is preferred as an initial therapy, as control of tumour bulk appears to delay progression of systemic disease. Chemotherapy is variably effective, depending on the underlying tumour type, with pancreatic neuroendocrine tumours exhibiting much better response rates than carcinoid tumours derived from other primary sites. Treatments appropriate for well-differentiated metastatic neuroendocrine tumours should be considered, including somatostatin analogues (e.g., octreotide, lanreotide), everolimus, sunitinib, or peptide receptor radiotherapy.[4]

Well-differentiated neuroendocrine tumours should be treated as carcinoid tumours.[2]​ See VIPoma.

Plus – supportive care

Back
ACUTE
|
favourable subtype: well-differentiated neuroendocrine tumours (likely neuroendocrine primary)
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

Supportive care should be initiated, ideally under the guidance of a palliative care physician or team.

Focus should be on palliation of symptoms.

Bone pain: typically requires treatment with a non-steroidal anti-inflammatory drug (NSAID), an opioid analgesic, or a corticosteroid, or a suitable combination of these agents. Zoledronic acid (a bisphosphonate) or denosumab can be given for pain due to bone metastases and to decrease risk of skeletal-related events such as fractures. Palliative radiation can also be considered.

Neuropathic pain: may respond to anticonvulsant therapy (e.g., gabapentin) or antidepressant therapy (e.g., duloxetine).

Local pain: can be treated with regional nerve blocks or radiotherapy.

Obstructive symptoms: are related to tumour mass or localised inflammation, and are common (e.g., bowel, biliary, and bronchial obstruction). Obstructive symptoms should be aggressively managed, using a multi-disciplinary approach, with interventional radiology, endoscopic or surgical intervention, radiotherapy, and pharmacotherapy, as appropriate.

Other symptoms requiring attention include fatigue, depression, anorexia, nausea, and delirium.

favourable subtype: adenocarcinoma with colorectal immunohistochemistry (likely colorectal primary)

1st line – colorectal cancer management protocol

Back
ACUTE
|
favourable subtype: adenocarcinoma with colorectal immunohistochemistry (likely colorectal primary)
1st line – 

colorectal cancer management protocol

Patients with immunohistochemistry suggestive of colorectal primary site (CDX2-positive, CK20-positive, CK7-negative) may benefit from chemotherapy regimens used for treatment of metastatic colorectal cancer (e.g., capecitabine plus oxaliplatin [CapeOX]; fluorouracil/folinic acid plus oxaliplatin [FOLFOX or FLOX] or irinotecan [FOLFIRI], with or without bevacizumab).​[2][3][46]​​​ See Colorectal cancer.

Plus – supportive care

Back
ACUTE
|
favourable subtype: adenocarcinoma with colorectal immunohistochemistry (likely colorectal primary)
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

Supportive care should be initiated, ideally under the guidance of a palliative care physician or team.

Focus should be on palliation of symptoms.

Bone pain: typically requires treatment with a non-steroidal anti-inflammatory drug (NSAID), an opioid analgesic, or a corticosteroid, or a suitable combination of these agents. Zoledronic acid (a bisphosphonate) or denosumab can be given for pain due to bone metastases and to decrease risk of skeletal-related events such as fractures. Palliative radiation can also be considered.

Neuropathic pain: may respond to anticonvulsant therapy (e.g., gabapentin) or antidepressant therapy (e.g., duloxetine).

Local pain: can be treated with regional nerve blocks or radiotherapy.

Obstructive symptoms: are related to tumour mass or localised inflammation, and are common (e.g., bowel, biliary, and bronchial obstruction). Obstructive symptoms should be aggressively managed, using a multi-disciplinary approach, with interventional radiology, endoscopic or surgical intervention, radiotherapy, and pharmacotherapy, as appropriate.

Other symptoms requiring attention include fatigue, depression, anorexia, nausea, and delirium.

favourable subtype: poorly differentiated carcinoma of the mediastinum or retroperitoneum in males <40 years (likely testicular primary)

1st line – testicular cancer management protocol

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ACUTE
|
favourable subtype: poorly differentiated carcinoma of the mediastinum or retroperitoneum in males <40 years (likely testicular primary)
1st line – 

testicular cancer management protocol

These patients should be assessed for testicular germ cell tumours (using alpha-fetoprotein [AFP] and beta-human chorionic gonadotrophin [hCG] serum tumour markers).​​[2][4]​​​ Male patients should be considered for testicular ultrasound, particularly if tumour markers are elevated, and primarily treated with curative intent with a cisplatin-based regimen (e.g., bleomycin, etoposide, cisplatin [BEP]).[2] See Testicular cancer.

Historically, many patients with poorly differentiated carcinoma with midline distribution actually had extragonadal germ cell tumours. European guidelines, therefore, suggest that the poorly differentiated carcinoma with midline distribution subtype should no longer be used.[3]

Plus – supportive care

Back
ACUTE
|
favourable subtype: poorly differentiated carcinoma of the mediastinum or retroperitoneum in males <40 years (likely testicular primary)
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

Supportive care should be initiated, ideally under the guidance of a palliative care physician or team.

Focus should be on palliation of symptoms.

Bone pain: typically requires treatment with a non-steroidal anti-inflammatory drug (NSAID), an opioid analgesic, or a corticosteroid, or a suitable combination of these agents. Zoledronic acid (a bisphosphonate) or denosumab can be given for pain due to bone metastases and to decrease risk of skeletal-related events such as fractures. Palliative radiation can also be considered.

Neuropathic pain: may respond to anticonvulsant therapy (e.g., gabapentin) or antidepressant therapy (e.g., duloxetine).

Local pain: can be treated with regional nerve blocks or radiotherapy.

Obstructive symptoms: are related to tumour mass or localised inflammation, and are common (e.g., bowel, biliary, and bronchial obstruction). Obstructive symptoms should be aggressively managed, using a multi-disciplinary approach, with interventional radiology, endoscopic or surgical intervention, radiotherapy, and pharmacotherapy, as appropriate.

Other symptoms requiring attention include fatigue, depression, anorexia, nausea, and delirium.

favourable subtype: blastic bone metastases with immunohistochemistry/serum prostate-specific antigen (likely prostate primary)

1st line – prostate cancer management protocol

Back
ACUTE
|
favourable subtype: blastic bone metastases with immunohistochemistry/serum prostate-specific antigen (likely prostate primary)
1st line – 

prostate cancer management protocol

Blastic bone metastases in older men (aged ≥40 years) with elevated prostate-specific antigen (PSA) most likely indicate a prostate primary.

Treatment with androgen deprivation therapy (with or without radiotherapy), or other treatments appropriate for newly diagnosed prostate cancer, should be administered.[4]​ See Prostate cancer.

Plus – supportive care

Back
ACUTE
|
favourable subtype: blastic bone metastases with immunohistochemistry/serum prostate-specific antigen (likely prostate primary)
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

Supportive care should be initiated, ideally under the guidance of a palliative care physician or team.

Focus should be on palliation of symptoms.

Bone pain: typically requires treatment with a non-steroidal anti-inflammatory drug (NSAID), an opioid analgesic, or a corticosteroid, or a suitable combination of these agents. Zoledronic acid (a bisphosphonate) or denosumab can be given for pain due to bone metastases and to decrease risk of skeletal-related events such as fractures. Palliative radiation can also be considered.

Neuropathic pain: may respond to anticonvulsant therapy (e.g., gabapentin) or antidepressant therapy (e.g., duloxetine).

Local pain: can be treated with regional nerve blocks or radiotherapy.

Obstructive symptoms: are related to tumour mass or localised inflammation, and are common (e.g., bowel, biliary, and bronchial obstruction). Obstructive symptoms should be aggressively managed, using a multi-disciplinary approach, with interventional radiology, endoscopic or surgical intervention, radiotherapy, and pharmacotherapy, as appropriate.

Other symptoms requiring attention include fatigue, depression, anorexia, nausea, and delirium.

favourable subtype: single metastatic lesion

1st line – definitive local therapy

Back
ACUTE
|
favourable subtype: single metastatic lesion
1st line – 

definitive local therapy

Patients presenting with a single metastatic lesion of unknown primary site are rare, and treatment should be individualised. However, the general consensus is to consider definitive local therapy, usually surgical; definitive radiotherapy may be appropriate depending on anatomical location.[2][3]​​​ Adjuvant chemotherapy may be considered to control metastatic foci that are not yet evident.[4]

Common sites of solitary lesions include the liver, adrenal gland, brain, and bone.

Treatment varies depending on suspected primary. Immunohistochemical testing can help to determine a likely primary site and guide treatment. A chemotherapy regimen with broad activity across tumour types (encompassing most likely sites of disease, such as occult lung carcinoma, or gastrointestinal tumours) is often preferred.

Plus – supportive care

Back
ACUTE
|
favourable subtype: single metastatic lesion
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

Supportive care should be initiated, ideally under the guidance of a palliative care physician or team.

Focus should be on palliation of symptoms.

Bone pain: typically requires treatment with a non-steroidal anti-inflammatory drug (NSAID), an opioid analgesic, or a corticosteroid, or a suitable combination of these agents. Zoledronic acid (a bisphosphonate) or denosumab can be given for pain due to bone metastases and to decrease risk of skeletal-related events such as fractures. Palliative radiation can also be considered.

Neuropathic pain: may respond to anticonvulsant therapy (e.g., gabapentin) or antidepressant therapy (e.g., duloxetine).

Local pain: can be treated with regional nerve blocks or radiotherapy.

Obstructive symptoms: are related to tumour mass or localised inflammation, and are common (e.g., bowel, biliary, and bronchial obstruction). Obstructive symptoms should be aggressively managed, using a multi-disciplinary approach, with interventional radiology, endoscopic or surgical intervention, radiotherapy, and pharmacotherapy, as appropriate.

Other symptoms requiring attention include fatigue, depression, anorexia, nausea, and delirium.

favourable subtype: oligometastatic disease

1st line – ablative surgery and/or radiotherapy

Back
ACUTE
|
favourable subtype: oligometastatic disease
1st line – 

ablative surgery and/or radiotherapy

European guidelines suggest that selected patients with oligometastatic disease may be managed using local ablative surgery and/or radiotherapy.[3][47]​​​ Candidate patients should satisfy the following criteria: local ablative treatment of all lesions by surgery and/or radiotherapy is deemed feasible; oligometastatic state has been confirmed by imaging including positron emission tomography/computed tomography and brain magnetic resonance imaging; number of metastases does not exceed five; no involvement of a diffuse organ, such as malignant pleural, peritoneal, or leptomeningeal carcinomatosis.[3]

Median event-free and overall survival of 15.6 and 52.5 months, respectively, has been reported following local ablative treatment of single-site and oligometastatic carcinoma of unknown primary.[47]

Plus – supportive care

Back
ACUTE
|
favourable subtype: oligometastatic disease
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

Supportive care should be initiated, ideally under the guidance of a palliative care physician or team.

Focus should be on palliation of symptoms.

Bone pain: typically requires treatment with a non-steroidal anti-inflammatory drug (NSAID), an opioid analgesic, or a corticosteroid, or a suitable combination of these agents. Zoledronic acid (a bisphosphonate) or denosumab can be given for pain due to bone metastases and to decrease risk of skeletal-related events such as fractures. Palliative radiation can also be considered.

Neuropathic pain: may respond to anticonvulsant therapy (e.g., gabapentin) or antidepressant therapy (e.g., duloxetine).

Local pain: can be treated with regional nerve blocks or radiotherapy.

Obstructive symptoms: are related to tumour mass or localised inflammation, and are common (e.g., bowel, biliary, and bronchial obstruction). Obstructive symptoms should be aggressively managed, using a multi-disciplinary approach, with interventional radiology, endoscopic or surgical intervention, radiotherapy, and pharmacotherapy, as appropriate.

Other symptoms requiring attention include fatigue, depression, anorexia, nausea, and delirium.

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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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