Would you treat endometrioid adenocarcinoma arising from an endometriosis lesion in a patient with prior hyst/BSO like an ovarian or endometrial primary?

For a patient with prior hyst/BSO and now an endometriosis-associated endometrioid adenocarcinoma, I would start by getting next-generation sequencing and MSI/MMR testing of the tissue specimen that was used to make the diagnosis. This would allow for additional information and the potential use of targeted therapies. In general, I think of treating endometriosis-associated cancers like ovarian cancer, but each case requires individualized care based on the disease burden, clinical status, prior treatment, etc. I would also want to truly ensure no other sites of disease with quality imaging, preferably a PETCT and MRI pelvis with and without contrast. 

Once a non-resectable, isolated disease is confirmed, I lean towards a treatment with a definitive approach when possible. So, I would look at the location of the lesion relative to the other pelvic structures (bladder, rectum, vasculature, ureter, etc.) and have a multidisciplinary discussion with my radiation oncology colleagues (i.e., present at the tumor board). If it was felt that rad onc could achieve curable intent dosing with appropriate sparing of other tissues to limit fistula/other complications, then based on data in ovarian cancer recurrence showing some in-field disease control, I would favor going with that approach (Johns et al., PMID 34169134, and Komura et al., PMID 30843318). If it was not felt that disease control could be achieved with definitive radiation, then I would start with systemic therapy and then revisit after a period of time to reassess for resectability vs. disease control with definitive radiation.

In general, endometrioid adenocarcinomas arising in endometriosis after hysterectomy/BSO are classified as peritoneal carcinomas and are treated like ovarian cancer. Tumor molecular studies may add critical information in directing primary therapy.

Background:

Numerous epidemiologic studies have demonstrated an association between endometriosis and ovarian cancer. (1) Data from the Ovarian Cancer Association Consortium (OCAC) showed a significant association between a history of endometriosis and specific histological subtypes of epithelial ovarian cancer (EOC). Associations were strongest with clear cell (odds ratio [OR] = 3.05) and endometrioid (OR = 2.04) EOC. (2) In contrast, studies have failed to demonstrate a definitive association of endometriosis with endometrial cancer. (3) Malignant transformation of extra-ovarian endometriosis is rare, reported to occur in 0.2% of cases with almost a quarter of reported cases arising in endometriosis involving extra-ovarian tissue. (4) Although poorly understood, carcinogenesis of ovarian endometriosis may differ from peritoneal endometriosis related endometrioid carcinoma. (4)

Mismatch repair (MMR) deficiency has been reported in up to 20% of patients with endometrioid EOCs compared with a lower rate (approximately 10%) in non-subtypes. (5) Studies have identified numerous gene mutations in endometriosis lesions. The ARID1A gene is thought to be involved in the progression of endometriosis to carcinoma. (6) Several investigators had demonstrated the presence of mutations in ARID1A enhances the response of PARP inhibitors to tumor cells, suggesting these patients may significantly benefit from the use of a PARPi. (6)

Recommendation:

All endometrioid carcinomas, regardless of primary tumor site, should be evaluated for MMR deficiency. In a patient with post hysterectomy/BSO endometrioid carcinoma, tumor molecular studies should also be performed along with genetic testing. Assuming she is not a candidate for a clinical trial, she should be offered systemic chemotherapy +/- immunotherapy. Surgery should be considered after systemic therapy if her cancer becomes potentially resectable. Adjuvant radiation therapy may be considered for local control. I would NOT treat her primarily with palliative radiation therapy but would first treat her in a potentially curative fashion with systemic therapy. She may also be a candidate for hormonal therapy if she suffers disease recurrence.

References:

1. Pearce et al., PMID 22361336
2. Mortlock et al., PMID 35492879
3. Poole et al., PMID 28299512
4. Benoit et al., PMID 16289714
5. Murphy and Wentzensen, PMID 21140452
6. Chen et al., PMID 34150634

I've seen a few cases where patients with a history of prior TAH for non-oncologic reasons 2+ years earlier developed endometrioid adenocarcinoma of the vaginal cuff, +/- nodal regional disease. 

We treat definitively similar to how we would approach vaginal recurrence of endometrial cancer assuming no peritoneal carcinomatosis or distant metastases.

If the condition is bulky, considering weekly concurrent radiosensitizing cisplatin may be advisable, despite GOG 0238's recommendations, due to a slightly different clinical scenario.

These cases generally require a full template-based interstitial brachytherapy procedure, as a cylinder is highly likely to be insufficient.