Postoperative Recurrences in Patients Operated for Pheochromocytomas and Paragangliomas: New Data Supporting Lifelong Surveillance

Simple Summary At least 10% of pheochromocytomas (PHEOs) and paragangliomas (PPGLs) may recur after the initial surgery. The optimal follow-up time for these tumors remains unknown. We present a cohort of recurrent PPGLs in a clinical care setting of a quaternary center. In this paper, we describe recurrence patterns based on tumor location (head and neck paragangliomas, thoracoabdominal paragangliomas, and pheochromocytomas). We report that the overall mean delay of recurrence was 9.7 years and that one-third of the cohort had a recurrence more than 10 years after the initial surgery. Additionally, 17.6% of recurrent PHEOs were smaller than the predicted cutoff for recurrence (5 cm). Finally, more than 50% of recurrent PPGLs harbored a germline mutation in a susceptibility gene. In sum, this paper supports that overall, the safest option remains a lifelong follow-up. Abstract At least 10% of pheochromocytomas (PHEOs) and paragangliomas (PGLs) (PPGLs) may recur after the initial surgery. Guidelines recommend annual screening for recurrence in non-metastatic tumors for at least 10 years after the initial surgical resection and lifelong screening in high-risk patients. However, recent data suggest that a shorter follow-up might be appropriate. We performed a retrospective analysis on patients with PPGLs who had local and/or metastatic recurrences between 1995 and 2020 in our center. Data were available for 39 cases of recurrence (69.2% female) including 20 PHEOs (51.3%) and 19 PGLs (48.7%) (13 head and neck (HNPGL) and 6 thoracoabdominal (TAPGL)). The overall average delay of recurrence was 116.6 months (14–584 months) or 9.7 years and the median was 71 months or 5.9 years. One-third of the cohort had a recurrence more than 10 years after the initial surgery (10–48.7 years). The average tumor size at initial diagnosis was 8.2 cm for PHEOs, 2.7 cm for HNPGLs, and 9.6 cm for TAPGLs. Interestingly, 17.6% of PHEOs were under 5 cm at the initial diagnosis. Metastatic recurrence was identified in 75% of PHEOs, 15.4% of HNPGLs, and 66.7% of TAPGLs. Finally, 12/23 (52.2%) patients with recurrence who underwent genetic testing carried a germline mutation. Overall, the safest option remains a lifelong follow-up.

[1]  Soo-Mi Park,et al.  SDHC phaeochromocytoma and paraganglioma: A UK‐wide case series , 2021, Clinical endocrinology.

[2]  F. Beuschlein,et al.  Personalized Management of Pheochromocytoma and Paraganglioma , 2021, Endocrine reviews.

[3]  K. Dreijerink,et al.  Recurrence rate of sporadic pheochromocytomas after curative adrenalectomy - a systematic review and meta-analysis. , 2020, The Journal of clinical endocrinology and metabolism.

[4]  M. Quartuccio,et al.  Recurrence of Pheochromocytoma With Metastases After Resection of Primary Tumor , 2020, Cureus.

[5]  C. Reddy,et al.  Recurrence and Progression of Head and Neck Paragangliomas after Treatment , 2020, Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery.

[6]  F. Beuschlein,et al.  Disease monitoring of patients with pheochromocytoma or paraganglioma by biomarkers and imaging studies. , 2020, Best practice & research. Clinical endocrinology & metabolism.

[7]  M. Morino,et al.  Predictors of recurrence of pheochromocytoma and paraganglioma: a multicenter study in Piedmont, Italy , 2019, Hypertension Research.

[8]  C. Jimenez.  Treatment for Patients With Malignant Pheochromocytomas and Paragangliomas: A Perspective From the Hallmarks of Cancer , 2018, Front. Endocrinol..

[9]  A. Godbout,et al.  Unusual presentation of pheochromocytoma: thirteen years of anxiety requiring psychiatric treatment , 2018, Endocrinology, diabetes & metabolism case reports.

[10]  A. Tischler,et al.  Pathology and genetics of phaeochromocytoma and paraganglioma , 2018, Histopathology.

[11]  S. Challinor,et al.  Clinical Predictors of Malignancy in Patients with Pheochromocytoma and Paraganglioma , 2017, Annals of Surgical Oncology.

[12]  S. Steinberg,et al.  SDHB mutation status and tumor size but not tumor grade are important predictors of clinical outcome in pheochromocytoma and abdominal paraganglioma , 2017, Surgery.

[13]  J. Lenders,et al.  MANAGEMENT OF ENDOCRINE DISEASE: Recurrence or new tumors after complete resection of pheochromocytomas and paragangliomas: a systematic review and meta-analysis. , 2016, European journal of endocrinology.

[14]  O. Dekkers,et al.  European Society of Endocrinology Clinical Practice Guideline for long-term follow-up of patients operated on for a phaeochromocytoma or a paraganglioma. , 2016, European journal of endocrinology.

[15]  T. Fojo,et al.  CHARACTERISTICS AND OUTCOMES OF METASTATIC SDHB AND SPORADIC PHEOCHROMOCYTOMA/PARAGANGLIOMA: AN NATIONAL INSTITUTES OF HEALTH STUDY. , 2016, Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists.

[16]  S. Buti,et al.  Very late recurrence of an apparently benign pheochromocytoma. , 2015, Journal of cancer research and therapeutics.

[17]  S. Hunter,et al.  Recurrence of Phaeochromocytoma and Abdominal Paraganglioma After Initial Surgical Intervention , 2015, The Ulster medical journal.

[18]  E. Berber,et al.  Predictors of recurrence in pheochromocytoma. , 2014, Surgery.

[19]  T. Fojo,et al.  The size of the primary tumor and age at initial diagnosis are independent predictors of the metastatic behavior and survival of patients with SDHB-related pheochromocytoma and paraganglioma: a retrospective cohort study , 2014, BMC Cancer.

[20]  W. Young,et al.  Pheochromocytoma and paraganglioma: an endocrine society clinical practice guideline. , 2014, The Journal of clinical endocrinology and metabolism.

[21]  P. Rustin,et al.  Germline mutations in FH confer predisposition to malignant pheochromocytomas and paragangliomas. , 2014, Human molecular genetics.

[22]  S. Bornstein,et al.  Plasma methoxytyramine: a novel biomarker of metastatic pheochromocytoma and paraganglioma in relation to established risk factors of tumour size, location and SDHB mutation status. , 2012, European journal of cancer.

[23]  E. Baudin,et al.  Metastatic Pheochromocytoma and Paraganglioma: Focus on Therapeutics , 2012, Hormone and Metabolic Research.

[24]  Q. Duh,et al.  One hundred two patients with pheochromocytoma treated at a single institution since the introduction of laparoscopic adrenalectomy. , 2010, Archives of surgery.

[25]  A. Verbeek,et al.  Metastases but not cardiovascular mortality reduces life expectancy following surgical resection of apparently benign pheochromocytoma. , 2008, Endocrine-related cancer.

[26]  W. Linehan,et al.  High frequency of SDHB germline mutations in patients with malignant catecholamine-producing paragangliomas: implications for genetic testing. , 2006, The Journal of clinical endocrinology and metabolism.

[27]  G. Chatellier,et al.  Year of diagnosis, features at presentation, and risk of recurrence in patients with pheochromocytoma or secreting paraganglioma. , 2005, The Journal of clinical endocrinology and metabolism.

[28]  S. Sheps,et al.  Long-term evaluation following resection of apparently benign pheochromocytoma(s)/paraganglioma(s) , 1990, World Journal of Surgery.