Postoperative stage 0 Hodgkin lymphoma. Is surgery alone a curative option?

Abstract

Classic Hodgkin lymphoma (HL) is a rare hematologic malignancy with high curative potential. Diagnosis is based on pathologic examination of an involved lymph node through microbiopsy or lymphadenectomy. The disease is then classified by PET/CT imaging as either early stage (Ann Arbor stage I or II) or advanced stage (Ann Arbor stage III or IV).¹ Standard treatment includes chemotherapy (CT), often combined with radiotherapy (combined modality treatment [CMT]), and is guided by established prognostic factors (i.e., patient age, presence of a large mediastinal mass, B symptoms, inflammation, or 4 or more involved sites). In addition, PET/CT is extensively used for prognostication,² treatment guidance,³ and response assessment.⁴

In some cases, patients undergo radical resection of affected lymph nodes or lesions and no further disease is found on PET/CT staging (i.e., “postoperative stage 0”). In 1965, Lacher reported the clinical outcomes of 11 patients with radical excision of Hodgkin's lymphoma.⁵ Eight of these 11 patients received postoperative treatment (radiation, chemotherapy, or a combination of both). Of the three patients who received no further treatment, two patients experienced disease relapse. Neither relapse occurred at the primary disease site. These observations were made before the development of modern imaging techniques, thus limiting the assessment of initial disease extension. Long-term remissions induced by surgery alone have recently been reported in patients with heavily pretreated relapsed or refractory disease⁶; however, such outcomes have not been reported for newly diagnosed patients.

Patients with postoperative stage 0 HL may meet the criteria for early-stage favorable disease, whether these patients should be treated as such is unknown. This is a rare clinical scenario, and these patients were excluded from clinical studies due to the absence of measurable disease.

In this study, we describe the characteristics and outcomes of 13 patients with postoperative stage 0 HL.

We retrospectively analyzed adult patients with localized HL who underwent radical resection (i.e., adenectomy). Only patients with negative postoperative staging PET/CT were included. Patients with nodular lymphocyte-predominant Hodgkin lymphoma were excluded from the analysis.

We identified 13 patients from seven centers in France who underwent complete surgical tumor resection between 2008 and 2023. All resections were performed with negative surgical margins. Staging PET/CT was systematically conducted for all patients, and no evidence of persistent disease was detected after surgery. Outcomes for the entire cohort are summarized in Table 1 and Figure 1. After a median follow-up of 55 months (6–154) after surgical resection, only one patient relapsed, who had not received any adjuvant treatment.

Postoperative treatment was given to 8/13 (61%) patients. All patients presented favorable disease criteria. Only one patient presented with B symptoms. Erythrocyte Sedimentation Rate was not available. Patients had no significant comorbidities. Three patients had mediastinal masses including two patients with thymic involvement, and one patient had extranodal disease of nasopharyngeal localization. Treatment comprised either CT or CMT. Chemotherapy consisted of 2 to 4 cycles of ABVD in all patients. Radiation therapy was given at 20 or 30 Gy. No patient was treated with radiotherapy alone. Among treated patients, no recurrences were observed over a median follow-up of 65 months.

Five (39%) patients did not receive further treatment after resection. One patient was 66 years old and thus met EORTC/LYSA unfavorable disease criteria. One patient was HIV positive with a negative viral load and normal CD4 count. Three patients had nodal disease and two patients had mediastinal masses. None of the patients had B symptoms. Reasons for no further treatment were patient refusal in two patients and physician choice in three patients. One patient in the watch and wait group experienced disease recurrence 8 months after surgery. Recurrence occurred at the original site with no evidence of disease spread on staging PET/CT. The patient was treated with two cycles of ABVD followed by 20 Gy radiotherapy and remains in remission 2 years after completion of treatment. The other four (80%) patients in the watch-and-wait arm remain in remission without further treatment after a median follow-up of 25 months. Two patients were still in remission after more than 5 years of follow-up.

Radical resection of Hodgkin lymphoma with no evidence of residual disease after PET/CT staging is a rare clinical situation. While such patients could be classified as favorable early-stage cases, they are excluded from clinical trials, leading to a lack of tailored therapeutic recommendations.

To the best of our knowledge, our study is the first to report the characteristics and outcomes of patients with postoperative stage 0 HL identified by negative postoperative PET/CT. As anticipated, patients had a favorable prognosis as evidenced by long-term remission. Our observations highlight the heterogeneity of treatment practice in these rare cases. Notably, over one-third of the cohort received no initial treatment; five patients received chemotherapy alone, while three received CMT. No patient was treated solely with radiotherapy.

Of the five patients who received no initial treatment, four remained in complete response at 20, 22, 75, and 103 months of follow-up, respectively. One patient had a local recurrence at 8 months and was successfully treated with 2 ABVD and 20 Gy radiotherapy. The patient remains in complete response at 20 months. These results suggest that surgery alone may be curative for most patients with postoperative stage 0 Hodgkin lymphoma although we cannot exclude the possibility of very late relapse.

Our cohort is too small to formulate any kind of therapeutic recommendation, while large studies are hampered by the paucity of cases. We found that a watch-and-wait strategy may be acceptable, notably for frail patients for whom chemotherapy and/or radiotherapy would be considered hazardous, provided that disease recurrence is closely monitored. This approach could limit the risk of both short- and long-term treatment-related toxicity, which is one of the major challenges in the management of HL.

Audrey Couturier and Guillaume Manson wrote the manuscript. Audrey Couturier, Alexandra Judet, Mohamed Touati, Thomas Nivet, Pierre Daufresne, Fabien Claves, Eric Durot, Rémy Duléry, and Guillaume Manson collected the data. Roch Houot reviewed the manuscript.

Guillaume Manson received honoraria from Kite-Gilead, Takeda, Bms, and Abbvie. Roch Houot received honoraria from Kite/Gilead, Novartis, Incyte, Janssen, MSD, Takeda, and Roche; and consultancy at Kite/Gilead, 63 Novartis, Bristol-Myers Squibb/Celgene, ADC Therapeutics, Incyte, and Miltenyi. Rémy Duléry reports personal fees from Takeda, Novartis, and Biotest and nonfinancial support from Gilead outside the submitted work. The remaining authors declare no competing financial interests.

This research received no funding.