Endometrial cancer is a malignancy of the inner lining of the uterus (the endometrium). It is the most common gynaecological cancer in urban India and is the fourth most common cancer in women globally. Its incidence is rising steeply with the increasing prevalence of obesity, type 2 diabetes, and sedentary lifestyles — all of which are associated with excess oestrogen, the main driver of the most common endometrial cancer subtype.
The prognosis for endometrial cancer is generally favourable: approximately 70% of cases are diagnosed at Stage I, when the cancer is confined to the uterus, and five-year survival at this stage exceeds 90–95%. The key to this good outcome is prompt investigation of the cardinal symptom — postmenopausal bleeding — without delay.
Dr. Nishtha Tripathi Patel performs comprehensive endometrial cancer surgery including total laparoscopic hysterectomy, bilateral salpingo-oophorectomy, and sentinel lymph node mapping at Sterling Hospitals and KD Hospital, Ahmedabad.
Trust Signals
- Specialty: Gynecologic Oncology
Molecular Subtypes (TCGA / ProMisE Classification)
Modern endometrial cancer management incorporates molecular subtyping, which has fundamentally changed how risk is assessed and treatment is personalised:
- POLE ultramutated — mutations in the POLE exonuclease domain create an extremely high tumour mutational burden. Despite sometimes high-grade histology, these tumours carry an excellent prognosis and may not require adjuvant treatment. Identified by POLE sequencing.
- MSI-high / dMMR (mismatch repair deficient) — caused by loss of mismatch repair proteins (MLH1, MSH2, MSH6, PMS2), either sporadic (often MLH1 promoter methylation) or Lynch syndrome. Identified by IHC or MSI testing. These tumours respond dramatically to immune checkpoint inhibitors (pembrolizumab, dostarlimab).
- Copy number low (p53 wild-type) — the most common group; corresponds to Grade 1–2 endometrioid carcinoma. Generally good prognosis with surgery alone for early-stage disease.
- Copy number high (p53 abnormal) — corresponds to serous carcinoma, clear cell, and Grade 3 endometrioid with TP53 mutation. High risk of relapse; requires adjuvant chemotherapy regardless of stage.
Molecular profiling (POLE, MMR IHC, p53 IHC, and NGS where indicated) is now recommended for all endometrial cancers at surgery and directly determines adjuvant treatment recommendations under the ESGO/ESTRO/ESP 2023 guidelines.
Risk Factors
The dominant risk factor for low-grade endometrioid carcinoma (Type I) is excess or unopposed oestrogen:
- Obesity — the most important modifiable risk factor. BMI >30 increases risk 2–4 fold; BMI >40 increases it up to 10-fold. Adipose tissue produces oestrone from androgens via aromatisation.
- Type 2 diabetes and insulin resistance — independently associated with endometrial cancer through elevated insulin levels, IGF-1, and oestrogen.
- Oestrogen-only HRT — significantly increases endometrial cancer risk. Combined oestrogen-progestogen HRT protects the endometrium.
- Tamoxifen — acts as a partial oestrogen agonist in the endometrium; long-term use (>5 years) increases endometrial cancer risk 2–3 fold.
- PCOS and chronic anovulation — prolonged oestrogen stimulation without progesterone from ovulation.
- Lynch syndrome — 40–60% lifetime endometrial cancer risk; endometrial cancer is often the sentinel cancer.
- Family history — first-degree relative with endometrial cancer approximately doubles personal risk.
- Endometrial hyperplasia — complex atypical hyperplasia (now termed “endometrial intraepithelial neoplasia”) carries a 30% risk of concurrent or subsequent endometrial cancer.
Diagnosis
Endometrial cancer diagnosis follows a structured pathway triggered by symptoms:
- Postmenopausal bleeding (PMB) — any vaginal bleeding 12+ months after the last period. Endometrial cancer is present in approximately 10% of women with PMB.
- Premenopausal abnormal uterine bleeding — heavy, irregular, or intermenstrual bleeding in women aged 40+ with risk factors warrants endometrial evaluation.
Investigations:
- Transvaginal ultrasound (TVS) — endometrial thickness ≤4 mm in a postmenopausal woman not on HRT has a negative predictive value >99% for endometrial cancer. Thickness >4 mm, or any focal lesion, requires tissue sampling.
- Endometrial biopsy (Pipelle) — outpatient sampling with ~90% sensitivity for carcinoma when the cavity is uniformly involved.
- Hysteroscopy + D&C — direct visualisation with targeted biopsy; preferred when Pipelle is non-diagnostic or a focal polyp/lesion is suspected. Day-case procedure under general anaesthesia.
- MRI pelvis — gold standard for preoperative staging: accurately predicts depth of myometrial invasion, cervical involvement, and enlarged lymph nodes. Determines surgical complexity.
- CT chest/abdomen/pelvis — for high-grade or clinically advanced cases to evaluate extra-uterine spread.
- Molecular testing — POLE mutation analysis, MMR IHC/MSI testing, p53 IHC, and NGS should be performed on all biopsy or surgical specimens.
Treatment
Surgery — the cornerstone for all stages:
- Total laparoscopic hysterectomy (TLH) + bilateral salpingo-oophorectomy (BSO) — standard surgery for all operable endometrial cancers. Dr. Nishtha performs this as a minimally invasive procedure, enabling hospital discharge within 24–48 hours for most patients.
- Sentinel lymph node (SLN) mapping — using indocyanine green (ICG) fluorescent dye injected into the cervix at the time of surgery, SLN mapping identifies the first draining lymph nodes for pathological examination. Now recommended as an alternative to full lymphadenectomy for low-to-intermediate risk disease; reduces risk of lower limb lymphoedema while maintaining staging accuracy.
- Full pelvic (and para-aortic) lymphadenectomy — performed for high-risk histologies, deep myometrial invasion, or when sentinel node mapping fails.
- Omentectomy and peritoneal staging — for high-grade histologies (serous, clear cell, carcinosarcoma, Grade 3 endometrioid) to exclude peritoneal spread.
Adjuvant treatment by risk group:
- Low risk (Stage IA, Grade 1–2, endometrioid, LVSI absent, p53 wt) — no adjuvant treatment required.
- Intermediate risk — vaginal brachytherapy (VBT) to reduce vaginal vault recurrence.
- High-intermediate and high risk — EBRT ± VBT ± chemotherapy depending on molecular subtype and staging.
- Advanced disease (Stage III/IV) — carboplatin + paclitaxel chemotherapy ± radiotherapy. For dMMR tumours, pembrolizumab/dostarlimab maintenance; for pMMR tumours, lenvatinib + pembrolizumab (second line).
Evidence & Research
Enhanced Surgical Protocol for Robotic Type 1 Modified Hysterectomy in Endometrial Carcinoma Cases
This academic work outlines an enhanced surgical protocol for robotic type 1 modified hysterectomy in endometrial carcinoma cases. It focuses on operative planning and technique refinement…
Treatment planning is guided by Dr. Nishtha Tripathi Patel, Consultant Gynecological Oncosurgeon in Ahmedabad.
Consultation available in Ahmedabad, Surat, Vadodara, and Gandhinagar.
Frequently Asked Questions
- What is the difference between endometrial hyperplasia and endometrial cancer?
Endometrial hyperplasia is an overgrowth of the endometrial lining caused by excess oestrogen. Simple hyperplasia without atypia carries very low cancer risk and often resolves with progestin therapy or correction of the oestrogen excess. Complex atypical hyperplasia (now termed “endometrial intraepithelial neoplasia” or EIN) carries a 30% risk of concurrent endometrial cancer and a significant risk of progression; hysterectomy is recommended for post-reproductive women. In women who wish to preserve fertility, high-dose progestin with close monitoring can be considered for EIN. Endometrial cancer is confirmed when malignant cells have invaded the endometrial stroma.
- Is endometrial cancer hereditary?
Most endometrial cancers are sporadic (not inherited). However, Lynch syndrome — an inherited condition caused by mutations in DNA mismatch repair genes — is responsible for approximately 3–5% of endometrial cancers. Women with Lynch syndrome have a 40–60% lifetime risk of endometrial cancer. Lynch syndrome should be suspected when endometrial cancer is diagnosed before age 50, when there is a personal or family history of colorectal, ovarian, or other Lynch-associated cancers, or when tumour MMR immunohistochemistry is abnormal. If Lynch syndrome is confirmed, cascade testing of first-degree relatives and colonoscopy surveillance are strongly recommended.
- What does "Grade 1, 2, or 3" mean for endometrial cancer?
Histological grade reflects how similar the cancer cells look to normal endometrial cells under the microscope. Grade 1 (well-differentiated) — cells closely resemble normal endometrium; grow slowly and respond well to treatment. Grade 2 (moderately differentiated) — intermediate. Grade 3 (poorly differentiated) — cells look very abnormal; more aggressive, higher risk of spread to lymph nodes, and more likely to require chemotherapy. Grade is one component of risk stratification for adjuvant treatment; it is now considered alongside molecular subtype (POLE, MMR, p53 status) for the most accurate risk assessment.
- Can I lose weight to reduce my risk of endometrial cancer?
Yes — weight loss is one of the most effective ways to reduce endometrial cancer risk. Studies show that substantial weight loss (through bariatric surgery or sustained lifestyle changes) reduces endometrial cancer risk by 50–80% in obese women, primarily by lowering circulating oestrogen levels. Combined oral contraceptives and levonorgestrel-releasing IUDs also protect the endometrium and are worth discussing with your gynaecologist if you have significant risk factors. For women already diagnosed with endometrial cancer, weight management after treatment improves cardiovascular outcomes and may reduce the risk of recurrence.
- What is sentinel lymph node mapping and why does it matter?
Sentinel lymph node (SLN) mapping is a technique that identifies the specific lymph nodes most likely to be the first site of spread from the uterus. A small amount of indocyanine green (ICG) fluorescent dye is injected into the cervix at the start of surgery. The dye travels through the lymphatic channels to the sentinel nodes, which are then identified under infrared light and removed for pathological examination. If the sentinel nodes are cancer-free, the remaining lymph nodes are very unlikely to contain cancer, avoiding the need for a full lymphadenectomy. This significantly reduces the risk of lower limb lymphoedema (a chronic complication of complete lymphadenectomy) while maintaining accurate staging information.