What is the prognosis of signet ring cell gastric carcinoma based on staging?

Prognosis of Signet Ring Cell Gastric Carcinoma by Stage

The prognosis of signet ring cell gastric carcinoma is stage-dependent: early-stage disease (Stage I) has excellent outcomes with 5-year survival rates of 96% and is actually associated with better prognosis than other gastric cancer histologies, while advanced-stage disease (Stage II-IV) carries significantly worse prognosis than other histologic types. 1, 2, 3

Early Stage Disease (Stage I)

Early signet ring cell gastric carcinoma demonstrates favorable prognosis that exceeds other gastric cancer histologies:

• 5-year survival rates for early signet ring cell carcinoma reach 96.1% compared to 89.6% for early non-signet ring cell types 2
• Lymph node metastasis rates in early disease are comparable or lower (10.7% vs 16.0%) than other histologic types 2
• Early gastric signet ring cell carcinoma comprises 29-46% of all signet ring cell cases, representing a higher proportion of early-stage presentation than other gastric cancers 2, 4
• Surgery alone with D2 lymphadenectomy achieves 71% 5-year survival for clinical Stage I disease, superior to perioperative chemotherapy (58%), neoadjuvant therapy (38%), or adjuvant therapy (52%) 1

Critical Staging Considerations

• A minimum of 15 lymph nodes must be examined for adequate staging, with optimal evaluation requiring at least 25 nodes 5, 6, 7
• The AJCC 8th edition TNM staging system should be used, with separate clinical (cTNM), pathologic (pTNM), and post-neoadjuvant (ypTNM) stage groupings 5
• Approximately 37% of clinical Stage I patients are upstaged to pathologic Stage II/III after surgery, but adjuvant therapy provides effective rescue with superior outcomes compared to preoperative treatment 1

Advanced Stage Disease (Stage II-IV)

Advanced signet ring cell carcinoma demonstrates significantly worse prognosis than other gastric cancer histologies:

• Among advanced gastric cancer patients, signet ring cell histology confers worse survival than other cell types 3
• Advanced disease shows higher rates of perineural invasion, lymph node metastasis, and hepatic metastasis compared to differentiated-type gastric carcinomas 3
• Overall 5-year survival for all signet ring cell carcinoma patients is 60.2%, though this reflects the favorable early-stage subset 4

Stage-Specific Prognostic Factors

Independent prognostic factors that determine survival across all stages include:

• TNM stage (hazard ratio 2.350, most powerful predictor) 3
• Lymph node metastasis status 4
• Curability of resection (R0 vs R1/R2) 4
• Patient age (hazard ratio 1.013) 3

Importantly, signet ring cell histology itself is NOT an independent prognostic factor when controlling for stage 4

Metastatic Disease (Stage IV)

Approximately 50% of gastric cancer patients present with advanced disease at diagnosis and have poor outcomes 5

• Performance status becomes the primary determinant of treatment approach, with best supportive care recommended for Karnofsky <60% or ECOG ≥3 5
• Systemic chemotherapy with fluoropyrimidine-platinum combinations is standard, though response rates remain poor in signet ring cell histology 7, 8
• HER2 testing should be performed, as trastuzumab plus chemotherapy improves outcomes in HER2-positive disease 7

Common Pitfalls in Prognostic Assessment

Avoid these critical errors when assessing prognosis:

• Do not assume signet ring cell histology automatically indicates poor prognosis—this is only true for advanced-stage disease 2, 3, 4
• Do not proceed without adequate lymph node evaluation (<15 nodes), as this leads to understaging and incorrect prognostic assessment 5, 6, 7
• Do not use pathologic staging criteria for clinical staging or post-neoadjuvant staging, as these have distinct prognostic implications 5
• Do not overlook the 37% upstaging rate from clinical to pathologic Stage I, which necessitates discussion of adjuvant therapy options 1

Prognostic Information by Staging System

The AJCC 8th edition provides distinct prognostic data for three staging scenarios based on datasets exceeding 25,000 patients 5:

• Clinical staging (cTNM): Based on 4,091 patients from National Cancer Database and Shizuoka Cancer Center, validated in 4,374 Japanese patients 5
• Pathologic staging (pTNM): Based on >25,000 patients, provides most accurate prognostic information 5
• Post-neoadjuvant staging (ypTNM): Based on 700 patients, presented in broad stage categories (I-IV) 5