Germline BAP1-positive patients: the dilemmas of cancer surveillance and a proposed interdisciplinary consensus monitoring strategy

Our plain-English summary of Germline BAP1-positive patients: the dilemmas of cancer surveillance and a proposed interdisciplinary consensus monitoring strategy, by P. Star, A. Goodwin, R. Kapoor, et al (European Journal of Cancer, 2018).

The study

• Authors: P. Star, A. Goodwin, R. Kapoor, R.M. Conway, G.V. Long, R.A. Scolyer, P. Guitera
• Journal: European Journal of Cancer
• Published: 2018;92:48-53
• Cited by: 32 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The germline BAP1 (BRCA1-associated protein-1) mutation and associated cancer pre-disposition syndrome was first described in 2011. Since then, physicians have considered this diagnosis for patients with a characteristic personal or family history of BAP1-associated tumours (mainly uveal and cutaneous melanoma, pleural/peritoneal mesothelioma, renal cell carcinoma and BAP1-deficient melanocytic lesions). However, a positive germline BAP1 mutation detection creates significant uncertainty in terms of appropriate cancer surveillance. A number of groups have proposed surveillance plans but important management dilemmas remain unresolved. The lifetime risk of developing cancer is not known and it is not clear if surveillance would lead to detecting cancer at an earlier stage or change survival outcomes. A consensus monitoring strategy was initially proposed at the Melanoma Institute Australia Melanoma Multidisciplinary Team meeting and later discussed with specialists in the field of cancer genetics, pathology, radiology, medical oncology, ophthalmology and dermatology. The objectives were to facilitate early diagnosis, incorporating where possible, clinically based and low/non-ionising radiation imaging modalities, applying the principles of a good screening test and a multidisciplinary focus.

Copyright © 2017 Elsevier Ltd. All rights reserved.

In plain English

This article was a 'Current Perspective', not a new study. The authors reviewed the literature and proposed a consensus cancer-surveillance plan for carriers of an inherited (germline) BAP1 mutation. The article links that mutation to pleural and peritoneal mesothelioma, uveal and cutaneous melanoma, and renal cell carcinoma. It was prompted by the need to manage one affected family's next generation. Citing an earlier review by Rai et al., they listed mesothelioma in 39 of 174 (22%) carriers. The plan proposed eye checks yearly from 16 and twice yearly from 30, twice-yearly skin checks from 18, and yearly abdominal and chest examination from 30. From 30 to 55, it offered either investigating symptoms or ultrasound or MRI every 2 years; after 55, it said to consider contrast CT or MRI every 2 years. It also advised avoiding smoking and asbestos exposure. The authors noted that the evidence came only from cohort and observational studies, that no evidence showed mesothelioma screening changed survival, and that carriers' risk could be overestimated. The authors concluded that BAP1 testing, if offered, should come with an optional surveillance protocol.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Perspective article: literature review and expert consensus proposal for a surveillance plan (no new patient data)
• Who was studied: People carrying a germline BAP1 mutation. The proposal was prompted by the next generation of one family with the mutation, discussed at Melanoma Institute Australia, Sydney.
• Exposure: No exposure was studied. The article concerns an inherited BAP1 mutation. Asbestos appears only in the recommendation that carriers avoid asbestos exposure.
• Main results:
  • Proposed eye surveillance: yearly review with an ophthalmologist specialising in uveal melanoma from age 16, and twice a year from age 30.
  • Proposed skin surveillance: twice-yearly dermatologist review with full-skin examination and total body photography from age 18.
  • Proposed annual abdominal and respiratory physical examination from age 30, looking for an abdominal mass, distention, fluid in the abdomen (ascites) or signs of fluid around the lungs (pleural effusion).
  • For ages 30 to 55: the option of investigating symptoms, or of imaging people without symptoms by ultrasound or MRI every 2 years.
  • After age 55: consider CT or MRI of the abdomen and chest, both with contrast, every 2 years. MRI may be preferred because of lower ionising radiation, but cost is an issue.
  • Background figure from an earlier review by Rai et al., not from this article: malignant mesothelioma in 39 of 174 germline BAP1 mutation carriers (22%).
  • Background figure cited from other studies: patients with germline BAP1 mutation-related mesothelioma had a 5-year survival of 47% (95% CI 24% to 67%), compared with 6.7% (95% CI 6.2% to 7.3%) for sporadic mesothelioma.
• The authors' conclusion: The authors concluded that the benefit of surveillance for rare, newly described diseases is difficult to assess. If BAP1 genetic testing is offered, it should be accompanied by an optional surveillance protocol. They invited feedback from other centres.
• Limitations the authors state:
  • The evidence behind surveillance recommendations comes only from cohort and observational studies (Level III and IV evidence).
  • There is no evidence that screening for pleural or peritoneal mesothelioma changes survival.
  • The prevalence of the mutation in the general population is unknown, so the cancer risk in carriers could be overestimated.
  • The benefit of surveillance plans for rare and newly described diseases is difficult to assess.

Topics

Medical terms in this study, explained in our Lexicon: BAP1, Peritoneal Mesothelioma, Carcinoma, BAP1 Tumor Predisposition Syndrome, Multidisciplinary Team, Pathology.

Related studies

• Prevalence and Preliminary Validation of Screening Criteria to Identify Carriers of Germline BAP1 Mutations — M.G. Zauderer, G. Jayakumaran, et al. (2019)
• CDKN2A and BAP1 germline mutations predispose to melanoma and mesothelioma — M. Betti, A. Aspesi, et al. (2016)
• Analysis of BAP1 Germline Gene Mutation in Young Uveal Melanoma Patients — C.M. Cebulla, E.M. Binkley, et al. (2015)
• Well-differentiated papillary mesothelioma: clustering in a Portuguese family with a germline BAP1 mutation — C. Ribeiro, S. Campelos, et al. (2013)
• Ocular melanoma and the BAP1 hereditary cancer syndrome: implications for the dermatologist — L.M. Martorano, R.R. Winkelmann, et al. (2014)
• Histomorphologic spectrum of BAP1 negative melanocytic neoplasms in a family with BAP1-associated cancer susceptibility syndrome — Z. Marušić, M. Buljan, et al. (2015)

Browse more research in European Journal of Cancer, or return to medical research.