(P 368) AGGRESSIVE PERINEAL ANGIOMYXOMA UNDERGOING SYSTEMIC TREATMENT: AN UPDATED REPORT OF 8-YEARS' EXPERIENCE IN A REFERRAL CENTER

Objective: Aggressive angiomyxoma (AA) is a are mesenchymal neoplasm, most commonly diagnosed in females and located in the perineal and pelvic region. Surgical excision, if feasible, is the preferred treatment option. However, up to 50% of patients (pts) experience local disease recurrence even after radical surgery, resulting in a significative quality of life (QoL) impairment due to uncontrolled pain and disease-related symptoms.
In relapsed or not resectable pts, hormonal treatment is often proposed to achieve local disease control, as positivity for estrogen (ER) and progesterone receptors (PgR) is common. Of note, some cases of androgen receptor (AR) positivity have been reported in males.
Due to disease rarity, data regarding disease management and hormonal treatment effectiveness are lacking, especially in advanced settings.
Five years ago, we reported the outcome of AA pts treated in our institution with hormonal therapy (HT): hereby, we present an updated report of previous results.

Methods: Clinical and pathological data of 36 pts diagnosed with perineal AA within 2004/01 and 2024/01 at our institution were retrospectively reviewed. Eligible patients had a pathologically confirmed diagnosis of AA. Descriptive statistical analyses were performed. Outcome results were presented in terms of median progression free survival (mPFS) and 1-year (1y) PFS probability for patients receiving first-line therapy (1Ltp). Due to the low number of events only univariate analyses were performed. Last follow-up update was performed on 2024/06/01.

Results: 36 pts (15 females; 2 males) were included in our sample. Median age at diagnosis was 42 years (range 19-59). ER and PgR were positive in 14/36 pts (82%), while AR resulted positive in all the two males (and were not evaluated in the others). 26 (72%) pts underwent surgical treatment: among resected pts, 9 (35%) experienced local recurrence. Overall, 17 pts (47%) started 1Ltp: 12 (71%) received gonadotropin-hormone release analogues (GnRHa), 4 (24%) letrozole (L), 1 (6%) tamoxifen plus GnRHa. At a mean follow-up (mFU) time of 8.4 years [interquartile range (IQR) 5.6–11.9], 4 pts (24%) experienced a complete response (CR), 9 (53%) a partial response (PR, 3 a stable disease (SD) (18%) and 2 (12%) had disease progression (PD) as best response (BR). Overall response rate (ORR) to 1Ltp was 76%; mPFS was 18 months [95% confidence interval (CI) 7.06 – N.R.] while 1-year PFS probability in our sample was 0.5 (95% CI 0.2 -1). 5 pts (29%) autonomously decided to stop treatment after 1 year: 2 had PD 3 months after treatment interruption; in the other 3 cases, SD was maintained. In 1pt HT was resumed after progression, thus achieving a new PR.

6 pts underwent 2L treatment (2Ltp): 2 of them received L plus GnRHa; 1 received the mTOR inhibitor sirolimus (S) plus L; 1 pt with AR positivity started off-label bicalutamide (B); 2 pts received GnRHa after progressing to L. ORR to 2Ltp was 33%: notably, one of the 2 pts treated with L plus GnRHa achieved a 10 years-lasting CR, while the other had SD. The 2 pts receiving GnRHa achieved SD. The pt receiving L plus S had a 12 years-lasting PR. However, S was precociously interrupted (2 yrs from 2Ltp start) due to pt’ decision, and treatment was prosecuted with L alone. The AR positive patient, who experienced short-time progression after 1Ltp with letrozole, was still on B with a 4 years-lasting SD at the last follow-up. No PD to 2Ltp were registered, and no death events were observed in our sample.

Conclusion: Hormonal systemic treatment still confirms to be a feasible and effective therapeutic option in AA pts recurring after surgery or not eligible to surgical intervention. Combination therapies (GnRHa plus L or S plus L) seem to be valuable alternatives in the 2L setting but more investigations are needed in this scenario. Furthermore, basing on our data, no recommendation about safe interruption of hormonal treatment can be made.
To this end, we encourage data sharing between referral centers and suggest to perform a thorough pathological characterization of hormone receptors expression in AA tissue specimens, including AR in all pts, in order to potentially identify predictive factors of treatment sensitivity.