How to manage recurrent Smooth Muscle Tumor of Uncertain Malignant Potential (STUMP) with Methylthioadenosine Phosphorylase (MTAP) loss in a postmenopausal woman after hysterectomy?

From the Guidelines

Management of recurrent Smooth Muscle Tumor of Uncertain Malignant Potential (STUMP) with Methylthioadenosine Phosphorylase (MTAP) loss in a postmenopausal woman after hysterectomy should focus on surgical resection of the recurrent tumor followed by close surveillance. The primary treatment approach should be complete surgical excision of all visible disease, which may involve cytoreductive surgery depending on the extent and location of recurrence. Following surgery, implement a surveillance protocol consisting of physical examinations every 3-6 months for the first 2-3 years, then annually, along with pelvic/abdominal imaging (MRI or CT scan) every 6 months initially, then annually for at least 5 years. For tumors with MTAP loss specifically, consider adjuvant therapy with PRMT5 inhibitors (currently in clinical trials) as these target the metabolic vulnerability created by MTAP deficiency. Hormonal therapy with aromatase inhibitors such as letrozole (2.5mg daily) or anastrozole (1mg daily) may be beneficial, particularly in estrogen receptor-positive tumors, and can be continued for 2-5 years, as supported by studies on endocrine treatment for postmenopausal patients 1. The rationale for this approach is that MTAP loss creates a metabolic dependency on the PRMT5 pathway, while STUMPs often express hormone receptors that can be targeted. Additionally, MTAP loss is associated with more aggressive behavior, justifying closer surveillance and consideration of adjuvant therapy despite the uncertain malignant potential classification. Recent guidelines for soft tissue sarcoma and GIST support the use of surgery as the cornerstone for the treatment of uterine sarcomas, with adjuvant therapy considered on a case-by-case basis 1. The use of adjuvant chemotherapy is not standard but may be proposed by specialized multidisciplinary teams in specific situations based on histologic subtype, clinical presentation, or in case of tumor fragmentation, as noted in guidelines for uterine sarcomas 1. Therefore, the management plan should be individualized, taking into account the patient's specific clinical scenario, the characteristics of the tumor, and the latest evidence-based recommendations.

From the Research

Management of Recurrent STUMP with MTAP Loss

• The management of recurrent Smooth Muscle Tumor of Uncertain Malignant Potential (STUMP) with Methylthioadenosine Phosphorylase (MTAP) loss in a postmenopausal woman after hysterectomy is a complex issue, and there is limited research available on this specific topic 2.
• However, it is known that STUMPs are a heterogeneous group of rare tumors that can occasionally recur, even years after hysterectomy 2.
• A study published in 2009 found that only 2 out of 16 STUMP cases recurred, and both of these cases had strong immunoreactivity for p16 and p53 2.
• The same study suggested that patients diagnosed with STUMPs should receive long-term surveillance 2.
• In terms of managing recurrent STUMP, there is no specific guidance available, but it is likely that treatment would depend on the individual case and the extent of the recurrence.
• Other studies have discussed the complications of hysterectomy, including infectious, venous thromboembolic, genitourinary, and gastrointestinal tract injuries, bleeding, nerve injury, and vaginal cuff dehiscence 3.
• Additionally, there have been reports of post-hysterectomy menstruation, which can be caused by various factors, including atrophic vaginitis, cervical stump cancer, and endometriosis of the vault 4.
• Radiotherapy has been used to treat centrally recurrent cervical cancer of the vaginal stump following hysterectomy, with tumor size being a significant prognostic factor 5.
• Secondary resection of the cervical stump after subtotal hysterectomy has also been reported, with indications including prolapse, spotting, and cervical dysplasia 6.

Considerations for Treatment

• The treatment of recurrent STUMP with MTAP loss would likely involve a multidisciplinary approach, taking into account the individual patient's circumstances and the extent of the recurrence.
• Further research is needed to determine the most effective treatment strategies for this specific condition.
• In the meantime, patients with a history of STUMP should be closely monitored for any signs of recurrence, and any symptoms or abnormalities should be thoroughly investigated 2, 3, 4, 5, 6.