Pretreatment evaluation, staging, and treatment stratification of classic Hodgkin lymphoma

INTRODUCTION — Classic Hodgkin lymphoma (cHL) includes the following histologic subtypes: nodular sclerosis cHL, lymphocyte-rich cHL, mixed cellularity cHL, and lymphocyte-depleted cHL.

This topic will discuss pretreatment evaluation, staging, and prognosis of cHL.

Clinical presentation and diagnosis of cHL is discussed separately. (See "Clinical presentation and diagnosis of classic Hodgkin lymphoma in adults".)

Evaluation of nodular lymphocyte-predominant Hodgkin lymphoma is discussed separately. (See "Nodular lymphocyte-predominant Hodgkin lymphoma: Clinical manifestations, diagnosis, and staging".)

PRETREATMENT EVALUATION — Pretreatment evaluation includes history and physical examination, laboratory studies, imaging, and specialized studies to assess the patient's fitness for treatment and to determine the disease stage.

Evaluation to diagnose cHL is presented separately. (See "Clinical presentation and diagnosis of classic Hodgkin lymphoma in adults", section on 'Evaluation'.)

History and physical examination — History should include the extent and duration of adenopathy, pruritus, fatigue, abdominal fullness/pain, and B symptoms (ie, fevers, sweats, weight loss). History should also include smoking history and comorbid conditions, including cardiovascular, respiratory, and neuropathic symptoms. Criteria for B symptoms are provided below. (See 'B symptoms' below.)

Performance status should be determined using either the Karnofsky or Eastern Cooperative Oncology Group (ECOG) scales (table 1).

Physical examination should evaluate the size, number, and specific regions of nodal enlargement (figure 1), presence of splenomegaly or hepatomegaly, and examination of the cardiac and respiratory systems.

Laboratory studies

●Hematology – Complete blood count (CBC) with differential count.

●Chemistry – Electrolytes, kidney and liver function tests, calcium, albumin.

●Inflammation – Erythrocyte sedimentation rate (ESR).

●Infectious:

•Hepatitis B – Hepatitis B surface antigen (HBsAg) and antibodies against hepatitis B core antigen (anti-HBc). For the patient who is HBsAg positive, further testing should include HBeAg, anti-HBe, and HBV DNA level. (See "Hepatitis B virus: Screening and diagnosis in adults", section on 'Serologic markers'.)

•Hepatitis C – Serologic testing for hepatitis C should include both antibody testing and hepatitis C RNA assays. (See "Screening and diagnosis of chronic hepatitis C virus infection", section on 'Diagnostic techniques'.)

•HIV – Human immunodeficiency virus (HIV) serology. (See "Initial evaluation of adults with HIV", section on 'HIV-related testing'.)

●Pregnancy test for females of childbearing age.

Cardiac function — Left ventricular ejection fraction (LVEF) should be evaluated by echocardiogram or radionuclide ventriculogram. LVEF should generally be ≥50 percent if doxorubicin-based chemotherapy is a consideration. (See "Tests to evaluate left ventricular systolic function".)

Pulmonary function tests — Pulmonary function tests (PFTs), including diffusing capacity (DLCO) should be performed if chemotherapy that includes bleomycin (eg, ABVD, BEACOPP) is a consideration. In general, DLCO ≥60 percent is acceptable for treatment with bleomycin.

PET/CT — Positron emission tomography/computed tomography (PET/CT) is the mainstay of imaging for staging cHL. PET is highly sensitive for the presence of cHL, but PET cannot be used to evaluate the brain (because of its avidity for fluorodeoxyglucose [FDG]) and because sites of infection or inflammation may also be PET positive. In some cases, diagnostic CT may clarify ambiguous PET findings or better define the relevant anatomy, as discussed below. (See 'Diagnostic CT' below and 'Magnetic resonance imaging' below.)

PET/CT should extend from skull base to mid-thigh, and results should be reported using the Deauville score (table 2), which uses FDG uptake in the mediastinal blood pool and liver as internal controls. Liver involvement may be suggested by focal FDG uptake (with or without disseminated nodules). Some experts suggest that PET/CT findings suspicious for liver involvement should be confirmed by ultrasound, intravenous contrast-enhanced CT, or MRI [1].

The high sensitivity and specificity of PET/CT for staging of cHL was confirmed in a meta-analysis of 20 studies [2]. If PET is unavailable, intravenous contrast-enhanced CT of chest, abdomen, and pelvis is an acceptable alternative for staging. (See 'Diagnostic CT' below.)

FDG-positive findings at locations that are inconsistent with a clinical presentation of cHL may require additional imaging, specialized studies, and/or pathologic confirmation. However, it should be recognized that unusual sites or patterns of involvement may be found in HIV-infected patients or other immunosuppressed individuals. (See "Clinical presentation and diagnosis of classic Hodgkin lymphoma in adults", section on 'Less common presentations'.)

Other imaging

Diagnostic CT — Diagnostic CT of the neck with intravenous contrast should be performed if PET is positive in the neck or if radiation therapy to the neck is a consideration. (See 'Magnetic resonance imaging' below.)

Some experts suggest a diagnostic quality CT (with or without intravenous contrast) of the chest, abdomen, and/or pelvis that includes all areas identified as abnormal on PET/CT. In some settings, a low-dose CT is performed at the time of PET (primarily for attenuation correction of PET images), and this may not adequately characterize the anatomy. A diagnostic quality CT (ie, higher photon strength) can better characterize ambiguous PET findings and/or determine the size of a mediastinal or other large tumor mass. (See 'Bulky disease' below.)

Magnetic resonance imaging — MRI can be used for anatomical imaging of PET-positive lesions to characterize involvement of certain organs (eg, brain, liver). (See 'PET/CT' above.)

●Central nervous system (CNS) – For patients with neurologic findings that are consistent with CNS involvement by cHL, the CNS should be evaluated by MRI (with and without gadolinium). Patients with neurologic findings should also undergo lumbar puncture with cytology. As described above, PET is not useful for evaluation of the CNS. (See 'PET/CT' above.)

CNS involvement with cHL is rare. However, various paraneoplastic syndromes (eg, cerebellar degeneration, chorea, neuromyotonia, limbic encephalitis, subacute sensory neuropathy, subacute lower motor neuropathy, stiff person syndrome) have been described in association with cHL. (See "Clinical presentation and diagnosis of classic Hodgkin lymphoma in adults", section on 'Less common presentations' and "Overview of paraneoplastic syndromes of the nervous system".)

If the patient is not a candidate for MRI, diagnostic CT with intravenous contrast is an acceptable alternative. (See 'Diagnostic CT' above.)

●Other sites – MRI is valuable for imaging the neck, liver, or other PET-positive sites where further anatomic definition is needed for staging or treatment planning.

Diagnostic quality CT, with or without intravenous contrast, is an acceptable alternative to MRI in such settings. (See 'Diagnostic CT' above.)

Chest radiography — A chest radiograph may be useful if a mediastinal mass is detected, but chest CT is generally used to determine if the mass constitutes "bulky" disease, as described below. (See 'Bulky disease' below.)

Other procedures

●Bone marrow evaluation – Bone marrow aspirate and biopsy is generally not required, because it has little or no therapeutic consequences [3,4].

We suggest bone marrow examination only when unexplained cytopenias are present in the setting of a PET that is negative for bone marrow involvement. A homogeneous pattern of uptake in the marrow should not be assumed to be marrow involvement, but skeletal PET/CT lesions at ≥3 sites should be interpreted as bone marrow involvement.

●Lumbar puncture – For patients with neurologic symptoms or signs, the CNS should be evaluated by lumbar puncture with cytology and by MRI, as described above. (See 'Magnetic resonance imaging' above.)

STAGING — Staging of cHL is essential for treatment stratification, as described below. (See 'Treatment stratification' below.)

Staging notation — Staging of cHL is based on the Lugano classification [1], which was derived from the Ann Arbor staging system with Cotswolds modifications [5,6].

Staging notation captures the extent of nodal involvement and other disease features (eg, B symptoms, bulky disease, and/or extranodal involvement):

●A numerical stage (I to IV) based on the sites of involvement (table 3). (See 'Nodal regions' below.)

•Stage I – Involvement of a single lymph node region (I) or of a single extralymphatic organ or site (I_E) without nodal involvement. A single lymph node region can include one node or a group of adjacent nodes.

•Stage II – Involvement of two or more lymph node regions on the same side of the diaphragm alone (II) or with involvement of limited, contiguous extralymphatic organ or tissue (II_E).

•Stage III – Involvement of lymph node regions or lymphoid structures on both sides of the diaphragm.

•Stage IV – Additional noncontiguous extralymphatic involvement, with or without associated lymphatic involvement.

For the purpose of treatment stratification, stages I and II are considered early stage (or limited stage) disease and stages III and IV are considered advanced stage disease, as described below. Whether stage II with bulky disease is treated as limited or advanced disease may be determined by certain prognostic factors. (See 'Early versus advanced disease' below.)

●Each disease stage is further notated according to:

•B symptoms – The presence ("B") or absence ("A") of systemic B symptoms is described below. (See 'B symptoms' below.)

•Bulky disease – The size of bulky disease should be reported, as described below. (See 'Bulky disease' below.)

•Extranodal involvement – The subscript "E" is used to describe extranodal extension in patients with limited stage cHL. "E" is not considered to be relevant in advanced-stage disease. (See 'Extranodal involvement' below.)

Nodal regions — Lymph node involvement is determined by physical examination and/or positron emission tomography/computed tomography (PET/CT). Diagnostic CT or magnetic resonance imaging (MRI) may be useful to further define the anatomy of certain PET-positive sites. Occasionally, biopsy of suspicious nodes is needed if imaging studies are indeterminate and treatment decisions would be affected by confirmation of involvement. Use of diagnostic CT or MRI for validation of PET findings is described above. (See 'PET/CT' above.)

Lymph nodes are divided into the following anatomic regions (figure 1); note that for staging purposes, the tonsils, Waldeyer's ring, and spleen are considered nodal tissue:

●Waldeyer's ring (tonsils, base of the tongue, nasopharynx)

●Ipsilateral cervical and supraclavicular

●Occipital and pre-auricular

●Infraclavicular

●Axillary and pectoral

●Mediastinal – Mediastinal nodes include thymus, prevascular, aortopulmonary; paratracheal, pretracheal, subcarinal, and posterior mediastinal involvement; all nodal disease within the mediastinum is considered to be a single lymph node region.

Internal mammary nodes are part of the lymphatic system of the chest wall and drain the diaphragm. Paravertebral nodes, although in the posterior mediastinum, also drain the chest wall and diaphragm.

●Hilar – Hilar nodes are considered separate from the mediastinum and should be considered to be "lateralized" (right hilar and left hilar nodes are separate regions) such that, when involved on both sides, constitute stage II disease.

●Para-aortic

●Spleen

●Iliac

●Ipsilateral inguinal and femoral

●Epitrochlear and brachial

●Mesenteric nodes and popliteal nodes are also considered as separate nodal areas, although involvement of these two regions is almost never seen in early stage disease.

B symptoms — Patients with the following are considered to have B symptoms:

●Unexplained fever >38°C during the previous month

●Recurrent drenching night sweats during the previous month

●Weight loss >10 percent of body weight within six months of diagnosis

Patients who do not meet any of the above criteria are described with the letter A.

Fatigue, pruritus, alcohol-associated pain, and other symptoms are not considered B symptoms.

Bulky disease — Bulky disease should be described according to its size (eg, 15 cm mediastinal mass). It is no longer necessary in the Lugano staging system to designate bulky disease by the subscript "X."

There are several systems for defining bulky disease. We consider bulky disease to be [1,7]:

●An abdominal node or nodal mass ≥10 cm in largest dimension as determined by CT, MRI, or ultrasound.

●Mediastinal mass on CT scan ≥10 cm or greater than one-third the internal transverse diameter of the thorax. We consider any of the following definitions of bulky disease to be acceptable for pretreatment evaluation of cHL:

•Mediastinal mass ratio (MMR) – MMR is the ratio of the maximum width of the mass and the maximum intrathoracic diameter; MMR >0.33 is defined as bulky disease [8].

•Mediastinal mass ≥10 cm – A single node or notable mass ≥10 cm is considered bulky disease.

•Cotswalds definition – Bulky mediastinal mass is defined as more than one-third of the internal transverse diameter of the thorax at the T5-T6 interspace on a postero-anterior (PA) chest radiograph [6].

Other definitions of bulk disease (eg, ≥5 or ≥7 cm) have been suggested but are not used in routine clinical care of cHL [9,10].

Extranodal involvement — The designation "E" refers to limited extranodal extension in patients with stage I or stage II disease.

The definition of limited extranodal disease is that which can be encompassed within an irradiation field that would be appropriate for nodal disease of the same anatomic extent. Limited extranodal disease is:

●Involvement of extralymphatic tissue on one side of the diaphragm by limited direct extension from an adjacent nodal site.

●An apparently discrete single extranodal deposit consistent with extension from a regionally involved node. If a single extralymphatic site is the only site of disease, the staging should be classified as I_E.

As an example, anterior extension of a mediastinal mass into the sternum or chest wall or extension to lung or pericardium should be recorded as extranodal extension (E). In contrast, diffuse or disseminated foci of one or more extralymphatic organs or tissues, with or without associated lymphatic involvement is designated as stage IV disease.

The presence of a single site of extranodal extension is considered to have a prognosis equivalent to that of nodal disease of the same anatomical extent. In contrast, disseminated extranodal disease (ie, stage IV) has an inferior prognosis. A retrospective study reported a striking difference in prognosis between patients with localized (ie, contiguous) extralymphatic organ involvement versus disseminated extralymphatic involvement [11].

Examples of staging — The following are provided as examples of the application of the Lugano staging system [1,7]:

●An asymptomatic patient with disease limited to nodes of the mediastinum with direct extension into the sternum would be staged as IA_E disease.

●An asymptomatic patient with bilateral cervical and right axillary lymph nodes with a small mediastinal mass would be staged as IIA disease.

●A symptomatic patient with night sweats, weight loss of 15 kg, bilateral cervical node enlargement, a 15 cm mediastinal mass on chest CT, involvement of the right hilum, an abdominal CT showing para-aortic and pelvic adenopathy with no definite involvement of the liver, and no evidence of bone marrow involvement on PET would be staged as IIIB (15 cm mediastinal mass).

●A symptomatic patient with disseminated extralymphatic involvement would be staged as IVB.

TREATMENT STRATIFICATION

Early versus advanced disease — For treatment stratification, cHL is divided into:

●Early stage (stages I and II) – Early stage cHL is defined as stages I or II. (See 'Staging notation' above.)

Patients with early stage disease are further stratified into favorable and unfavorable categories. Definitions of favorable and unfavorable disease (table 4) are provided below. (See 'Favorable early stage' below and 'Unfavorable early stage' below.)

Whether patients with stage II with bulky disease should be treatment as limited stage versus advanced disease is a source of controversy, as discussed below. (See 'Advanced stage disease' below.)

●Advanced stage (stages III and IV) – Patients with advanced cHL should be evaluated with the international prognostic score (IPS), as described below. (See 'International Prognostic Score (IPS)' below.)

Early stage — Stages I and II. (See 'Staging notation' above.)

Unfavorable early stage — The most common definitions of unfavorable stage I to II disease are those of the European Organization for the Research and Treatment of Cancer (EORTC) and the German Hodgkin Study Group (GHSG). No prognostic model for early stage cHL has proven itself superior for risk stratification and either of these definitions is acceptable:

●EORTC – The EORTC defines the unfavorable prognostic group as one or more of the following risk factors [1]:

•Age >50

•Large mediastinal adenopathy (defined as mediastinal mass width measuring >1/3 of the thoracic width at the T5-6 level)

•Erythrocyte sedimentation rate (ESR) ≥50 mm/h and no B symptoms or (ESR ≥30 mm/h in those with B symptoms)

•≥4 sites of involvement

●GHSG – The GHSG defines the unfavorable prognostic group as one or more of the following risk factors [12]:

•Large mediastinal adenopathy (defined as mediastinal mass measuring >1/3 of the maximum thoracic diameter)

•ESR ≥50 mm/h and no B symptoms or (ESR ≥30 mm/h in those with B symptoms)

•≥3 sites of involvement

•Extranodal involvement

A retrospective study applied the GHSG, EORTC, and National Comprehensive Cancer Network (NCCN) models (table 4) to 1173 patients with early stage cHL [13]. The three models classified similar percentages of patients as having unfavorable prognosis early stage cHL (56, 55, and 57 percent, respectively). Each model had comparable high sensitivity (79 to 84 percent) but modest specificity (53 to 55 percent) for identifying patients with inferior progression-free survival (PFS) and overall survival (OS).

Management of early stage unfavorable prognosis cHL is described separately. (See "Treatment of unfavorable prognosis early (stage I-II) classic Hodgkin lymphoma in adults".)

Favorable early stage — Favorable prognosis early stage cHL is defined by the absence of the criteria for unfavorable disease. (See 'Unfavorable early stage' above.)

Management of early stage favorable prognosis cHL is described separately. (See "Treatment of favorable prognosis early (stage I-II) classic Hodgkin lymphoma".)

Advanced stage disease — Advanced stage cHL includes patients with stages III to IV. Patients with advanced stage cHL should be evaluated with the IPS, as described below. (See 'International Prognostic Score (IPS)' below.)

Several cooperative groups include patients with stage II disease with one or more risk factors in their advanced-stage trials [9,14,15].

Management of advanced stage cHL is discussed separately. (See "Initial treatment of advanced (stage III-IV) classic Hodgkin lymphoma".)

PROGNOSTIC SCORING

International Prognostic Score (IPS) — Patients with advanced stage cHL should be evaluated with the IPS. The IPS does not need to be applied to patients with early stage cHL; rather, treatment stratification of patients with stages I to II cHL is described above. (See 'Early stage' above.)

The IPS was developed from a retrospective review of clinical features and outcomes in >5000 patients with cHL (table 5) (calculator 1) [16]:

●Serum albumin <4 g/dL

●Hemoglobin <10.5 g/dL

●Male sex

●Age >45 years

●Stage IV disease

●White blood cell count ≥15,000/microL

●Absolute lymphocyte count <600/microL and/or <8 percent of the total white blood cell count

One point is given for each of the characteristics above (total score of 0 to 7). Following are rates of freedom from progression (FFP) and OS in an analysis of 740 patients with advanced stage cHL treated with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) from 1980 to 2010 [17]. At a median follow-up of 77 months, FFP and OS at five years correlated with IPS as follows:

●No factors – FFP 88 percent, OS 98 percent (8 percent of patients)

●One factor – FFP 84 percent, OS 97 percent (26 percent of patients)

●Two factors – FFP 80 percent, OS 91 percent (26 percent of patients)

●Three factors – FFP 74 percent, OS 88 percent (21 percent of patients)

●Four factors – FFP 67 percent, OS 85 percent (12 percent of patients)

●Five or more factors – FFP 62 percent, OS 67 percent (7 percent of patients)

Other prognostic factors — Pathologic features have been evaluated as potential prognostic factors for cHL, but none is routinely applied in clinical practice.

●Tumor grade – Grading schemes have been proposed for cHL, but there is no clinical mandate to apply them in practice and they are not used for stratifying treatment. The British National Lymphoma Investigation (BNLI) and the GHSG include various cellular features (eg, composition of the inflammatory infiltrate, atypia of Hodgkin/Reed-Sternberg cells) to grade cHL [18,19].

●Inflammatory infiltrate – The numbers of infiltrating macrophages and eosinophils in the inflammatory infiltrate may have prognostic value in cHL. Several studies have reported that increased numbers of macrophages in the inflammatory infiltrate correlated with a higher risk of relapse [20-23].

Increased expression of proteins in the programmed cell death pathway by Hodgkin/Reed-Sternberg cells might also be related to overall clinical prognosis [24,25]. In one study, the presence of high numbers of active caspase-3 positive HRS cells was associated with higher rates of complete remission and OS [26].

●Epstein-Barr virus (EBV) – The presence of EBV is generally associated with inferior prognosis in cHL, compared to patients who are EBV-negative. Approximately one-third to one-half of cases are EBV-positive, based on immunostaining for latent membrane protein (LMP)-1 or EBV-encoded RNA (EBER) [27,28]. The highest percentage of EBV-positive cases are in children <10 years and adults >55 years [27-29]. In a study of 922 patients with cHL, EBV positivity was independently associated with increased HL-specific mortality and inferior survival in adults ≥45 years [30]. A prospective study also reported that patients with EBV-positive tumors had inferior survival [31]. A cooperative group study of adults with newly diagnosed cHL reported that plasma EBV viral genome copy number may have prognostic value in cHL [32].

OTHER PRETREATMENT MANAGEMENT

Counseling — All patients with cHL should be counseled to stop smoking. (See "Overview of smoking cessation management in adults".)

Patients should be offered psychosocial counseling similar to that described for the survivor of cHL. (See "Approach to the adult survivor of classic Hodgkin lymphoma", section on 'Psychosocial issues'.)

Immunization — Immunization for the adult with cancer is discussed separately. (See "Immunizations in adults with cancer".)

Fertility preservation — Individuals with childbearing potential should receive counseling about the potential effect of cHL and treatment on fertility and options for fertility preservation. Although ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) chemotherapy is not associated with infertility, referral may be warranted in the event of refractory disease or relapse that requires other types of treatment.

It is useful to note that some males with cHL (especially those with B symptoms or other adverse features) may have impaired quantity or quality of sperm prior to treatment [33]. However, sperm quality before treatment is generally good enough for future fatherhood, and males should be encouraged to participate in sperm banking.

For females, cryopreservation of ovarian tissue/oocytes and other approaches are discussed separately. (See "Fertility and reproductive hormone preservation: Overview of care prior to gonadotoxic therapy or surgery".)

SOCIETY GUIDELINE LINKS — Our approach to staging is consistent with those of the United States National Comprehensive Cancer Network, Lugano classification, and other international groups [1,34].

Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Lymphoma diagnosis and staging" and "Society guideline links: Management of Hodgkin lymphoma".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient education" and the keyword(s) of interest.)

●Beyond the Basics topics (see "Patient education: Hodgkin lymphoma in adults (Beyond the Basics)")

SUMMARY

●Classic Hodgkin lymphoma (cHL) – cHL includes the following histologic categories:

•Nodular sclerosis cHL

•Lymphocyte-rich cHL

•Mixed cellularity cHL

•Lymphocyte-depleted cHL

Nodular lymphocyte-predominant Hodgkin lymphoma is discussed separately. (See "Nodular lymphocyte-predominant Hodgkin lymphoma: Clinical manifestations, diagnosis, and staging".)

●Pretreatment evaluation – Pretreatment evaluation includes (see 'Pretreatment evaluation' above):

•Clinical – History, physical examination, and screening laboratory studies. (See 'History and physical examination' above and 'Laboratory studies' above.)

•Heart and lung function – (See 'Cardiac function' above and 'Pulmonary function tests' above.)

•Positron emission tomography (PET)/computed tomography (CT) – (See 'PET/CT' above.)

•Other – In selected cases, diagnostic CT, chest radiography, and/or other procedures may be used in staging cHL. (See 'Diagnostic CT' above and 'Magnetic resonance imaging' above and 'Chest radiography' above and 'Other procedures' above.)

●Staging – Staging is based on the Lugano criteria (table 3), which describes the sites of involvement (stages I to IV), presence of B symptoms (fever, sweats, weight loss), bulky disease, and extranodal extension. (See 'Staging' above.)

Description of nodal regions (figure 1) and criteria for B symptoms, bulky disease, and extranodal extension are provided above. (See 'B symptoms' above and 'Bulky disease' above and 'Extranodal involvement' above.)

●Stratification – For the purpose of treatment, patients with cHL are stratified according to stage:

•Early stage (stages I or II)

-Unfavorable early stage – Based on European Organization for the Research and Treatment of Cancer (EORTC) or German Hodgkin Study Group (GHSG), as described above (see 'Unfavorable early stage' above)

-Favorable early stage – Absence of unfavorable criteria (see 'Favorable early stage' above)

•Advanced stage (stages III and IV) – Patients with advanced stage cHL should be evaluated with the International Prognostic Score (IPS). (See 'Advanced stage disease' above.)

●Prognostic scoring – IPS, which is applied only for patients with advanced stage cHL, includes patient age, sex, disease stage, and measurements of serum albumin, hemoglobin, white blood cell count, and absolute lymphocyte count (table 5) (calculator 1). (See 'International Prognostic Score (IPS)' above.)

●Other pretreatment management – Other pretreatment management includes immunization and counseling for smoking cessation and fertility preservation. (See 'Other pretreatment management' above.)

ACKNOWLEDGMENT — The editorial staff at UpToDate acknowledges the late Peter M Mauch, MD for his previous contributions to this topic.