What is the treatment and prognosis for a female patient with FIGO (International Federation of Gynecology and Obstetrics) stage 3C gynecologic cancer?

FIGO Stage 3C Endometrial Cancer: Definition, Treatment, and Prognosis

Definition and Staging

FIGO Stage IIIC endometrial cancer is defined by the presence of metastases to regional lymph nodes, specifically subdivided into Stage IIIC1 (pelvic lymph node involvement only) and Stage IIIC2 (para-aortic lymph node involvement with or without pelvic node involvement). 1, 2

• Stage IIIC1 indicates metastasis to pelvic lymph nodes only 1, 2
• Stage IIIC2 indicates metastasis to para-aortic lymph nodes, with or without pelvic lymph node involvement 1, 2
• This staging is based on the 2009 FIGO surgical/pathologic staging system, which replaced the older 1988 system 1, 2
• The distinction between IIIC1 and IIIC2 is prognostically significant, with Stage IIIC1 showing better survival (57%) compared to Stage IIIC2 (49%) 1

Required Surgical Staging

Complete surgical staging must include the following components to accurately diagnose Stage IIIC disease:

• Total hysterectomy with bilateral salpingo-oophorectomy 3
• Pelvic and para-aortic lymph node assessment (dissection or sampling) 3, 2
• Peritoneal washings/cytology (though positive cytology no longer upstages disease) 1, 3, 2
• Thorough abdominal exploration 3
• Assessment of depth of myometrial invasion 3

Treatment Recommendations

For Stage IIIC endometrial cancer, platinum-based chemotherapy is strongly recommended as the primary adjuvant treatment, with sequential radiotherapy for patients with positive lymph nodes. 1

Chemotherapy Approach

• Platinum-based chemotherapy regimens (carboplatin/paclitaxel or cisplatin/doxorubicin) are the standard of care for Stage III-IV disease 1
• The combination of carboplatin and paclitaxel is preferred due to better tolerability compared to cisplatin/doxorubicin/paclitaxel regimens 1
• Chemotherapy significantly improves progression-free survival and overall survival compared to radiation therapy alone 1, 3

Radiation Therapy

• Sequential radiotherapy following chemotherapy is recommended for patients with positive lymph nodes 1
• Pelvic radiotherapy increases locoregional control 1, 3
• Extended-field radiation to para-aortic regions may be considered for Stage IIIC2 disease, as para-aortic failures have been documented 4

Combined Modality Approach

Recent evidence supports combined chemoradiation:

• The PORTEC-3 trial demonstrated that concurrent chemoradiation (pelvic RT with cisplatin followed by carboplatin/paclitaxel) improved 5-year failure-free survival to 69.3% for Stage III disease compared to 58% with RT alone 1
• For Stage IIIC specifically, combined modality therapy showed 78.7% 5-year overall survival versus 69.8% with RT alone 1

Prognosis and Survival Data

The 5-year overall survival for Stage IIIC endometrial cancer ranges from 57-61%, with Stage IIIC1 having better outcomes than Stage IIIC2. 1, 5

Survival Statistics

• Stage IIIC1 (pelvic nodes only): 5-year overall survival of 57-70% 1, 5
• Stage IIIC2 (para-aortic nodes): 5-year overall survival of 49-57% 1, 5
• Overall Stage IIIC: 5-year overall survival of 60-61%, with recurrence-free survival of 58% 5
• Disease-specific survival at 5 years is approximately 72% 5

Prognostic Factors

Key factors affecting survival in Stage IIIC disease include:

• Age: Older patients have worse outcomes 5, 6
• Histologic type: Non-endometrioid histology (serous, clear cell) significantly worsens prognosis 5, 6
• Depth of myometrial invasion: Greater than 50% invasion is an independent predictor of survival 5, 6
• Extranodal disease: Presence of positive peritoneal cytology and/or adnexal metastases in addition to nodal disease dramatically reduces 3-year survival to 39% versus 93% without extranodal disease 6

Patterns of Recurrence

Distant metastases represent the most common site of failure in Stage IIIC disease, occurring in approximately 15-21% of patients, followed by para-aortic node recurrence (20.6%). 5, 7

• Distant recurrence: 15-21% of patients 5, 7
• Para-aortic lymph node recurrence: 20.6% 7
• Pelvic lymph node recurrence: 8.8% 7
• Vaginal recurrence: 5.9% 7
• Median time to recurrence: 17 months (range 9.5-42 months) 7
• Notably, 100% of recurrences occurred outside the radiation field in one series, supporting the need for systemic chemotherapy 5

Critical Clinical Pitfalls

• Do not rely on positive peritoneal cytology alone for staging, as it no longer upstages disease in the 2009 FIGO system, though it remains an important prognostic factor when combined with nodal disease 1, 2, 6
• Always distinguish between Stage IIIC1 and IIIC2, as survival differs significantly and may influence treatment decisions regarding extended-field radiation 1
• Recognize that pelvic radiation alone is insufficient for Stage IIIC disease given the high rate of distant failures; systemic chemotherapy is essential 5, 7
• Consider the presence of extranodal disease (positive cytology, adnexal involvement) in addition to nodal metastases, as this dramatically worsens prognosis and may warrant more aggressive multimodality therapy 6