A 65-year-old woman with a BMI of 38 kg/m² and history of type 2 diabetes presents with abnormal uterine bleeding. Endometrial biopsy confirms grade 3 endometrioid adenocarcinoma with deep myometrial invasion (>50%) and lymphovascular space invasion. Staging CT shows no distant metastases. She undergoes total abdominal hysterectomy with bilateral salpingo-oophorectomy and pelvic lymphadenectomy. Pelvic lymph nodes are negative. What is the drug of choice for adjuvant treatment in this patient?

Explanation

## High-Risk Early-Stage Endometrial Cancer — Adjuvant Chemotherapy **Key Point:** Grade 3 endometrial cancer with deep myometrial invasion and LVSI is classified as **high-risk early-stage disease** and requires adjuvant chemotherapy (carboplatin–paclitaxel), regardless of lymph node status. ### Risk Stratification and Adjuvant Therapy Decision Tree ```mermaid flowchart TD A[Early-stage endometrial cancer]:::outcome --> B{Grade 3 OR deep MI OR LVSI?}:::decision B -->|No| C[Low/intermediate risk]:::outcome C --> D[Observation or vaginal brachytherapy]:::action B -->|Yes| E[High-risk disease]:::outcome E --> F{Histology?}:::decision F -->|Endometrioid| G[Carboplatin + Paclitaxel]:::action F -->|Serous/Clear cell| H[Carboplatin + Paclitaxel ± RT]:::action G --> I[Improved RFS and OS]:::outcome H --> J[Improved RFS and OS]:::outcome ``` ### Why Carboplatin–Paclitaxel Is Indicated **High-Yield:** This patient has **three high-risk features:** 1. **Grade 3** — highest nuclear grade 2. **Deep myometrial invasion (>50%)** — strong predictor of lymph node metastases and distant recurrence 3. **LVSI** — independent risk factor for metastatic disease Even with **negative pelvic nodes**, these patients have a 20–30% risk of recurrence (pelvic, para-aortic, or distant) with surgery alone. ### Evidence for Chemotherapy | Trial/Study | Population | Intervention | Outcome | |---|---|---|---| | **GOG-99** | Stage I–II, high-risk | Vaginal brachytherapy vs. observation | Reduced vaginal recurrence; no OS benefit | | **PORTEC-1** | Stage I–II, high-risk | External RT vs. observation | Reduced locoregional recurrence; no OS benefit | | **GOG-209** | Stage III–IV | Carboplatin–paclitaxel vs. doxorubicin–cisplatin | Similar efficacy; carboplatin–paclitaxel preferred (less toxicity) | | **PORTEC-3** | High-risk stage I–II or stage III | Chemotherapy + RT vs. RT alone | **Improved RFS and OS with combined therapy** | **Clinical Pearl:** PORTEC-3 demonstrated that in high-risk early-stage endometrial cancer, **carboplatin–paclitaxel chemotherapy** improves both recurrence-free survival and overall survival compared to radiotherapy alone. This is the landmark trial supporting chemotherapy in this population. **Mnemonic:** **HiRiCh** — **Hi**gh-risk endometrial cancer → **Ri**quires **Ch**emotherapy (carboplatin–paclitaxel).