Table 3.

Management of recurrences.

Recurrence	ESGO-ESTRO-ESP, ESMO	NCCN
Local or regional	No prior radiotherapy exposure: EBRT + brachytherapy (1st choice) +/− CHT * Superficial vaginal cuff recurrences: brachytherapy alone * Consider surgery for solitary easily accessible superficial vaginal tumor prior to RT for better local symptom control.	No prior radiotherapy exposure: EBRT + brachytherapy (1st choice) +/− CHT
	Previous BRT only, surgical exploration: Disease confined to vagina or paravaginal soft tissues, EBRT with brachytherapy boost. If locoregional nodal disease, to pelvic or para-aortic lymph node, EBRT +/− CHT If upper abdominal or peritoneal recurrence, CHT + palliative RT if necessary.	Previous BRT only, surgical exploration: Disease confined to vagina or paravaginal soft tissue, EBRT plus brachytherapy If locoregional nodal disease, to pelvic or para-aortic lymph node, EBRT +/− CHT If upper abdominal or peritoneal recurrence, CHT + palliative RT if necessary.
	Previous RT at the recurrence site, surgical exploration with radical resection when feasible + CHT +/− RT. If surgery is not feasible, radical re-irradiation.	Previous RT at the recurrence site, surgical exploration with radical resection when feasible + CHT +/− RT. If surgery is not feasible, radical re-irradiation.
Isolated distant metastasis	Surgical resection if feasible (+/− CHT + RT) or selected stereotactic RT	Surgical resection if feasible or selected stereotactic RT
Disseminated metastasis/further recurrences	Low grade, asymptomatic, hormone receptor-positive metastases: hormonal therapy (CHT to progression) Symptomatic, high grade, large volume metastases: multiagent CHT (if tolerated) * carboplatin–paclitaxel first line. * consider single-agent options if indicated. No standard treatment for second-line therapy, but doxorubicin and paclitaxel are considered the most active therapies. MSI-H/dMMR tumors: pembrolizumab Platinum-based CHT re-challenge if relapse > 6 months since last platinum-based therapy Clinical trials or best supportive care are appropriate	Low grade, asymptomatic, hormone receptor-positive metastases: hormonal therapy (CHT to progression) Symptomatic, high grade, large volume metastases: multiagent CHT (if tolerated) * carboplatin–paclitaxel first line. No standard treatment for second-line therapy MSI-H/dMMR tumors: pembrolizumab (or nivolumab) Recurrent HER2 serous carcinoma: carboplatin/paclitaxel/trastuzumab bevacizumab or temsirolimus approved single-agent biologic therapy for progression on previous cytotoxic CHT. Clinical trials or best supportive care are appropriate.