Observation May Be Preferrable to Surgery in Certain Cases of Desmoid Tumor Fibromatosis

The local recurrence rate after surgical excision was similar to the rate of progression with active surveillance in patients with extra-abdominal desmoid tumor fibromatosis (DTF), suggesting that observation may be sufficient in some cases of DTF, according to findings from a retrospective, multicenter study published in BMC Cancer.

“Local recurrence rate after surgery was similar to progression rates under observation. Hence, observation in DTF seems to be justified, considering surgery in cases of dimensional progression in 2 consecutive controls (3 and 6 months) and in painful lesions, with particular attention to lesions around the shoulder girdle,” Pierluigi Cuomo, MD, PhD, an orthopedic surgeon and honorary senior lecturer in the Department of Bioengineering at the Imperial College of London, and co-authors wrote in the publication.

DTF is a rare, soft tissue tumor that originates from the clonal proliferation of spindle cells. The malignancy can occur sporadically from a mutation in the gene that encodes ß-catenin or can be inherited from a mutation in the APC genes that are associated with familial adenomatous polyposis syndrome.

Sporadic DTF is often locally aggressive but lacks metastatic potential. Sporadic cases tend to occur in the limbs, girdle, trunk, and neck, whereas familial cases tend to occur intra-abdominally and involve the mesentery and/or intestinal wall.

Surgical excision remains a controversial treatment intervention for patients with DTF because the condition is uncommon, benign, and can spontaneously regress. However, the disease is locally aggressive and is associated with a high rate of local recurrence ranging from 15% to 77% within a median recurrence periods of 14.1 months.

“Although DTF has been described a long time ago, it is still a hot and challenging topic because of local aggressiveness and high recurrence rates, which [has] made [it] difficult to achieve a consensus on the best management, so far,” wrote Cuomo and co-authors.

Notably, alternative interventional approaches, such as radiation therapy, cryotherapy, isolated limb perfusion, and traditional pharmacologic therapies have not demonstrated a benefit in outcome for patients with primary disease. Kinase inhibitors may have utility in advanced or recurrent disease; however, additional data are needed.

Funded by the European Musculoskeletal Oncology Society (EMSOS), the study investigators aimed to retrospectively analyze the outcomes of patients with DTF after various treatment interventions, assess prognostic factors for recurrence after surgery, and assess prognostic factors for progression during active surveillance.

Overall, data from 7 European institutions representing 6 countries––Italy, Hungary, the Netherlands, Ukraine, Austria, and Switzerland––were evaluated.

Patients were evaluated in 6 groups based on prior medical treatment, including surgery (n = 257; Group 1), chemotherapy (n = 17; Group 2), hormone therapy (n = 15; Group 3), nonsteroidal anti-inflammatory drugs (NSAIDs; n = 16; Group 4), radiotherapy (n = 13; Group 5), and active surveillance (n = 70; Group 6).

Among all patients (n = 388), the mean age was 37.5 years (range, 3-85) and the majority were female (n = 240).

Most patients presented with primary DTF (n = 296) vs recurrent disease (n = 90). Patients had a mean diagnosis delay of 13.8 months (range, 0-120) after the presentation of symptoms.

Overall, 190 patients underwent an incisional biopsy vs 170 who underwent a needle biopsy. ß-catenin was not evaluated in 247 patients, was negative in 11 patients, and was positive in 112 patients.

Tumor locations included the arm (n = 37), foot (n = 11), forearm (n = 18), hand/wrist (n = 3), leg (n = 35), pelvic girdle (n = 72), shoulder girdle (n = 119), and thigh (n = 73). Most patients had deep tumors (n = 324) vs extra-fascial (n = 51). The size of tumors included those less than 5 cm (n = 113), 5 to 10 cm (n = 180), and larger than 10 cm (n = 89).

Overall, nerve involvement was present in 67 patients and neurologic symptoms were present in 45 patients.

Previous local events included surgery (n = 68) and trauma (n = 33).

Of the female patients, 33 patients were menopausal, 4 were pregnant, and 11 were recently pregnant.

Finally, pain was reported as: absent (n = 135), mild (n = 133), moderate (n = 71), or severe (n – 18).

Resection margin data that was available for 233 patients in group 1 revealed that 40.3% of patients achieved an R0 resection, 39.9% achieved an R1 resection, and 19.7% of patients achieved an R2 resection.

Outcome data was available for 375 patients. Notably, in group 1, after a median follow-up of 100 months, 146 patients achieved remission with surgical excision, 11 had a stable lesion after debulking, and 91 progressed.

In group 2, 2 patients achieved remission with chemotherapy, 13 had SD, and 2 progressed. In group 3, 1 patient achieved remission with hormone therapy, 8 had SD, and 6 progressed. In group 4, 2 patients achieved remission with NSAIDs, 9 had SD, and 5 progressed. In group 5, 5 patients achieved remission with radiation therapy, 7 had SD, and 1 progressed.

In group 6, 8 patients achieved remission with active surveillance, 32 had stable disease (SD), and 27 progressed.

Regarding group 1, patients who were older at diagnosis had a higher likelihood of achieving remission following surgery compared with patients who were younger at diagnosis (P = .02). Moreover, the likelihood of achieving a remission after surgery increased by 2.3% every year.

Additionally, patients with recurrent disease experienced significantly more recurrences (57.6%) vs patients with primary presentation (29.9%; P = .023).

Finally, patients whose lesions were larger than 10 cm had a significantly lower rate of remission (50.9%) compared with patients whose lesions were smaller than 5 cm (65.3%) or in between 5 cm and 10 cm (59.2%; P = .003).

In group 6, patients with a painful lesion who received active surveillance had a higher rate of disease progression (43.1%) vs those without pain (28%). Moreover, patients whose lesions were located at the shoulder had a higher rate of progression (64.7%) compared with those who had lesions located in other anatomic regions (P = .01).

“The present multicentric study, besides confirming already known conclusions on prognostic factors of surgically treated lesions, interestingly highlighted the importance of pain in the natural history of DTF and should then be of inspiration for further research, possibly leading to its optimal management,” concluded Cuomo and co-authors.

Reference

1. Cuomo P, Scoccianti G, Schiavo A, et al. Extra-abdominal desmoid tumor fibromatosis: a multicenter EMSOS study. BMC Cancer. 2021;21(437). doi:10.1186/s12885-021-08189-6