What is the best course of action for a 61-year-old female (F) with a history of clear cell Endometrial Cancer (Endometrial CA) status post (s/p) 6 cycles of Chemotherapy and 3 cycles of Immunotherapy, presenting with fever, leukocytosis (elevated white blood cell count) and neutrophilia (elevated neutrophil count), left inguinal pain, and left leg swelling, with a PET scan showing a probable abscess in the left abdominal area and inflamed or enlarged lymph nodes, considering cancer recurrence versus infection?

Management of Suspected Abscess vs. Cancer Recurrence in Post-Treatment Clear Cell Endometrial Cancer

This patient requires urgent image-guided aspiration or biopsy of the left abdominal lesion to definitively distinguish between infection and cancer recurrence, followed by immediate empiric broad-spectrum antibiotics given the acute infectious presentation with fever, leukocytosis, and neutrophilia. 1, 2

Immediate Diagnostic Approach

Obtain tissue diagnosis urgently through CT- or ultrasound-guided aspiration/biopsy of the left abdominal probable abscess before initiating definitive cancer-directed therapy. 1 This is critical because:

• The clinical presentation with fever, leukocytosis, and neutrophilia one week ago strongly suggests an infectious process that requires drainage and antimicrobial therapy 1
• Clear cell endometrial cancer is a high-risk histology with aggressive behavior, making recurrence plausible, but the acute inflammatory presentation is atypical for isolated cancer recurrence 1
• PET scan findings of "probable abscess" with inflamed/enlarged lymph nodes are non-specific and cannot reliably differentiate infection from malignancy 1

Concurrent Management Steps

Start empiric broad-spectrum antibiotics immediately covering gram-negative and anaerobic organisms while awaiting culture results, given the clinical syndrome of fever with leukocytosis and suspected intra-abdominal abscess. 1

Complete staging workup with:

• CT chest/abdomen/pelvis with IV contrast (if not already done comprehensively) to assess full extent of disease and identify other potential sites of infection or metastases 1, 2
• Complete blood count, comprehensive metabolic panel, and inflammatory markers (CRP, ESR) 1, 2
• Blood cultures if febrile 1

Risk Stratification Context

This patient has multiple high-risk features for recurrence:

• Clear cell histology is an aggressive variant with patterns of failure mimicking ovarian cancer 1
• Post-chemotherapy and immunotherapy status indicates advanced or high-risk disease at presentation 1
• Recurrence typically occurs within first 3 years, with disseminated or extrapelvic recurrences being common in high-risk histologies 1, 2

However, the acute presentation with fever and marked leukocytosis/neutrophilia is more consistent with bacterial infection, potentially complicated by immunotherapy-related immune dysregulation. 3, 4

Management Algorithm Based on Biopsy Results

If Abscess Confirmed (Infection Only):

Proceed with source control:

• Image-guided percutaneous drainage if abscess is accessible and >3-4 cm 1
• Continue targeted antibiotic therapy based on culture sensitivities for 4-6 weeks 1
• Monitor inflammatory markers and repeat imaging in 4-6 weeks to confirm resolution 1
• Resume routine surveillance schedule for clear cell endometrial cancer with history/physical every 3 months and symptom-directed imaging 1

If Cancer Recurrence Confirmed:

Treatment depends on extent and location:

• Isolated pelvic/regional recurrence (if previously non-irradiated): Consider pelvic exenteration if surgically resectable with acceptable morbidity in fit patients, or radiotherapy with 5-year survival rates of 30-80% 2

• Disseminated or extrapelvic recurrence: Initiate systemic chemotherapy with carboplatin/paclitaxel as preferred first-line regimen, though response rates are modest (32-40%) particularly after prior chemotherapy exposure 1, 2, 4

• Consider molecular profiling for emerging targeted therapies and immunotherapy rechallenge options, particularly given prior immunotherapy exposure 2, 4, 5

If Both Infection and Cancer Present:

Prioritize infection control first:

• Complete abscess drainage and antibiotic course before initiating cancer-directed therapy 1
• Delay systemic chemotherapy until infection resolved and patient clinically stable 1
• Consider holding immunotherapy permanently if infection was related to immune-related adverse event (though vaginal mucositis and hemophagocytic lymphohistiocytosis are more commonly reported than intra-abdominal abscess) 3, 6

Critical Pitfalls to Avoid

• Do not empirically treat as cancer recurrence without tissue diagnosis, as this would delay appropriate infection management and expose the patient to unnecessary chemotherapy toxicity 1, 2
• Do not assume PET-avid lymph nodes represent metastases in the setting of acute infection, as inflammatory nodes are FDG-avid and indistinguishable from malignant nodes on imaging alone 1
• Do not restart immunotherapy without careful consideration if infection is confirmed, as immunotherapy can cause rare but severe complications including hemophagocytic lymphohistiocytosis and severe mucositis 3, 6
• Do not delay drainage of a drainable abscess, as source control is essential and antibiotics alone are often insufficient for large abscesses 1

Prognosis Considerations

If this represents cancer recurrence, prognosis is guarded with clear cell histology in the recurrent setting. 1, 2 Longer relapse-free interval (if >12-18 months from initial treatment) and isolated recurrence patterns are associated with better survival, but disseminated disease typically has median survival of 12-15 months with chemotherapy. 1, 2