Desmoid tumours in familial adenomatous polyposis and what every colorectal surgeon should know - snapshot interview with Gabriela Möslein

Interview by Vittoria Bellato.

Professor Gabriela Möslein is ESCP's General Secretary, Chair of the EHTG (European Hereditary Tumour Group) and Director of the Centre for Hereditary Tumours at Bethesda Hospital in Germany. She has dedicated her professional focus towards hereditary colorectal cancer both as a researcher and scientific communicator and is acknowledged worldwide for her contribution and expertise.

ESCP’s Colorectal Hereditary Cancer month launched on the 22 June with a great interview with Gabriela about hereditary colorectal cancer enriched by valuable advice to trainers and some interesting considerations regarding women in surgery. Available to view here> 

We took the opportunity to request some additional expert clinical advice from Gabriela regarding the management of desmoid tumours (DT) - a rare tumour that any colorectal surgeon treating familial adenomatous polyposis (FAP) patients may have seen and usually will not know how to best manage.

Vittoria Bellato: Dear Gabriela, thank you for sharing with us your knowledge and expertise on such a poorly understood topic as desmoid tumours. We are looking for practical hands-on advice for colorectal surgeons. What kind of a tumour is this and is it actually benign or malignant?

Gabriela Möslein: From a surgical point of view desmoids must be seen as a neoplasm that fulfills all criteria of local malignancy: infiltrative growth, very hard tissue, frequently no sheaths or planes to guide surgical resection. However, desmoids come in lots of shapes and sizes and relate to their anatomical location. The worst ones are intra-abdominal, in the mesentery of the small bowel and are synonymously referred to as 'aggressive fibromatosis'. Importantly, desmoid tumours do not metastasise, but can be multiple. Also, they have a marked tendency to recur locally, even after R0 resection with a wide margin.

VB: In your experience, can you tell us how frequent desmoid tumours (DT) are in FAP patients and when are they clinically relevant?

GM: They are certainly much more frequent in FAP patients than generally perceived. In literature you will find a range of estimates that relate to the diagnostic methods applied and systematic long-term follow-up.

Intra-abdominal desmoid tumours will affect between 10-30% of patients diagnosed with FAP and the risk of developing a desmoid tumour is 852 times higher in a patient affected by FAP that of the general population. [1-4]

Intriguingly, DTs mostly occur after abdominal surgery, since trauma of any kind triggers growth. Obviously the unavoidable requirement of prophylactic colorectal surgery is the most important precursor event.

VB: So DTs are truly frequent in FAP patients. With the wide adoption of screening programmes and the increasing use of prophylactic total colectomy-proctocolectomy to prevent the onset of colon adenocarcinoma in FAP patients, desmoid tumours have become the primary cause of death in approximately 11% of FAP patients after prophylactic surgery. [5,6] I wonder, if it makes a difference, if surgery is performed laparoscopically or conventionally and if colectomy and IRA triggers less DT growth than the more invasive proctocolectomy?

GM: Both aspects would seem to be relevant to the extent of surgical trauma, which as I have pointed out previously acts as an obvious trigger for desmoid growth. Interestingly both technical aspects have been inconclusive, with contradictory findings in literature. The lack of inconsistency relates to small series, retrospective data, unsystematic follow-up but also on the inability to visualise smaller intra-abdominal desmoids. To be honest, I have found desmoid scarring or precursor lesions in almost all FAP patients that have undergone previous major surgery. If these will progress or not after a secondary or tertiary surgery cannot be anticipated.

To answer your question with a recent metaanalysis by Xie et al [10] analysing data from 1989-2019 including almost 1000 evenly distributed patients, the risk of DTs was equal for IRA and IPAA. In my experience the important factor and clue is actually if the surgeries led to complications and reoperations or not. The cumulative surgical trauma at a specific site seems to be the more important trigger, which is the driver for my not constructing loop ileostomies for IPAA any more.

VB: FAP diagnosis after DT is much rare scenario than the contrary, do you recommend FAP testing after a diagnosis of a single DT?

GM: With genetic testing becoming so much more available and less costly, the answer is yes. If you have limited ressources or need to base this on clinical information, I would answer that you can base this on multiplicity (will be FAP), association with trauma, family history for desmoids, and age. The younger the patient is, the higher the probability for a genetically based etiology (FAP).

VB: Taking into account that DT seems to recur more frequently and become more aggressive with each surgical intervention, some societies recommend an initial conservative approach for patient diagnosed with FAP that developed intrabdominal desmoid tumour, in which circumstances is this advisable? [7-10]

GM: We have a very standardised initial conservative approach which has proven to be successful in 85% of all DT patients [11]. Also if the medication is taken for a long enough period of time, we do not see recurrence, which is thet major offset of most other therapies. You may have good short-term results with radiotherapy (intra-abdominal DTs are a contraindication) or chemotherapy or even aggressive chemotherapy, but a very high rate of recurrence, as with surgery. Our standard relies on the administration of high-does SERMs in combination with sulindac. My advice is to treat these patients in centers with sufficient experience since we do sometimes complement our standard treatment with an additional therapy. However let me assure you, that there are only very few indications to resect abdominal or intra-abdominal desmoid tumours.

VB: In your #ColorectalLIVE interview on the 22nd of June, you mention adopting (Ta)TME and avoiding ileostomies during prophylactic proctocoledctomies to try to reduce incidence of DT. What aspects a surgeon must consider when decide to operate on a patient with diagnosis of FAP?

GM: Regarding the topic of this interview, DTs, you should do everything you can to prevent desmoid growth. Essentially this means that you will want to see:

• An uneventful primary surgery with no complications, especially no requirement of revisions
• Laparoscopic approach
• Exact anastomic site of resection and anastomosis (ileoanal - avoid rectal remnant)
• IPAA for classical FAP (avoid a second major completion surgery)
• Remove the colorectal mesentery
• Avoid routine ileostomy
• Follow-up on your patients (functional results, desmoid tumors etc.)

VB: You have provided us with some very practical advice for surgeons. In order to improve the situation of desmoid patients - which research study can you suggest?

GM: I really think that it is more than timely to implement a global registry for FAP-associated desmoid patients, containing the mutational information, age of occurrence, details of the colorectal surgery performed including the complications, documentation of site and size and molecular profile of the DT, method of follow-up, documentation of growth speed and robust treatment information.

VB: Any final comment or recommendation that you wish to add?

GM: I would like to point out that if you coincidentally encounter a desmoid at surgery for FAP patients, do not resect the small bowel. I have seen far too many FAP patients with short bowel syndrome (SBS) due to surgeons heroically but falsely resecting DTs. There are a number of conservative treatments available and the consequences of SBS are more serious than tolerating a desmoid, especially in the light of very effective options and also a spontaneous remission rate actually.

VB: Thank you for your time and your insight, Professor Gabriela Möslein.

References

1. Nieuwenhuis MH, Lefevre JH, Bülow S, et al. Family history, surgery, and APC mutation are risk factors for desmoid tumors in familial adenomatous polyposis: an international cohort study. Dis Colon Rectum. 2011;54(10):1229-1234. doi:10.1097/DCR.0b013e318227e4e8
2. Bertario L, Russo A, Sala P, et al. Genotype and phenotype factors as determinants of desmoid tumors in patients with familial adenomatous polyposis. Int J Cancer. 2001;95(2):102-107. doi:10.1002/1097-0215(20010320)95:2<102::aid-ijc1018>3.0.co;2-8
3. Koh PK, Loi C, Cao X, et al. Mesenteric desmoid tumors in Singapore familial adenomatous polyposis patients: clinical course and genetic profile in a predominantly Chinese population. Dis Colon Rectum. 2007;50(1):75-82. doi:10.1007/s10350-006-0759-z
4. Gurbuz AK, Giardiello FM, Petersen GM, et al. Desmoid tumours in familial adenomatous polyposis. Gut. 1994;35(3):377-381. doi:10.1136/gut.35.3.377
5. Nugent KP, Spigelman AD, Phillips RK. Life expectancy after colectomy and ileorectal anastomosis for familial adenomatous polyposis. Dis Colon Rectum. 1993;36(11):1059-1062. doi:10.1007/BF02047300
6. Parc Y, Piquard A, Dozois RR, Parc R, Tiret E. Long-term outcome of familial adenomatous polyposis patients after restorative coloproctectomy. Ann Surg. 2004;239(3):378-382. doi:10.1097/01.sla.0000114216.90947.f6
7. Vasen HF, Möslein G, Alonso A, et al. Guidelines for the clinical management of familial adenomatous polyposis (FAP). Gut. 2008;57(5):704-713. doi:10.1136/gut.2007.136127
8. Church J, Simmang C; Standards Task Force; American Society of Colon and Rectal Surgeons; Collaborative Group of the Americas on Inherited Colorectal Cancer and the Standards Committee of The American Society of Colon and Rectal Surgeons. Practice parameters for the treatment of patients with dominantly inherited colorectal cancer (familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer). Dis Colon Rectum. 2003;46(8):1001-1012. doi:10.1007/s10350-004-7273-y
9. Guillem JG, Wood WC, Moley JF, et al. ASCO/SSO review of current role of risk-reducing surgery in common hereditary cancer syndromes. J Clin Oncol. 2006;24(28):4642-4660. doi:10.1200/JCO.2005.04.5260
10. Xie M, Chen Y, Wei W, et al. Does ileoanal pouch surgery increase the risk of desmoid in patients with familial adenomatous polyposis? [published online ahead of print, 2020 May 20]. Int J Colorectal Dis. 2020;10.1007/s00384-020-03578-y. doi:10.1007/s00384-020-03578-y
11. Quast DR, Schneider R, Burdzik E, Hoppe S, Möslein G. Long-term outcome of sporadic and FAP-associated desmoid tumors treated with high-dose selective estrogen receptor modulators and sulindac: a single-center long-term observational study in 134 patients. Fam Cancer. 2016;15(1):31-40. doi:10.1007/s10689-015-9830-z