What is the treatment for signet cell adenocarcinoma?

Treatment of Signet Ring Cell Adenocarcinoma

Treatment of signet ring cell adenocarcinoma is site-specific and requires aggressive surgical resection as the primary modality, with multimodality therapy tailored to the organ of origin and disease stage.

Gastric Signet Ring Cell Carcinoma

Hereditary Diffuse Gastric Cancer (HDGC)

• For patients with CDH1 germline pathogenic variants and family history of diffuse gastric cancer, prophylactic total gastrectomy between ages 20-30 years is the only effective prevention strategy 1
• Prophylactic total gastrectomy should be considered even for CDH1 carriers without family history of diffuse gastric cancer or with only lobular breast cancer family history 1
• Surgery is not generally recommended for patients older than 70 years 1
• The surgical technique must achieve complete eradication of all gastric mucosa with intra-operative confirmation of esophageal squamous mucosa proximally and duodenal mucosa distally 1
• D1 lymphadenectomy is recommended to balance morbidity reduction with adequate staging 1
• Baseline endoscopy is mandatory to exclude established gastric cancer, which would require full staging with consideration of neoadjuvant treatment 1
• Annual endoscopic surveillance is safe in specialist HDGC referral centers for patients who defer surgery, with prophylactic total gastrectomy recommended if signet ring cell lesions are identified 1

Sporadic Gastric Signet Ring Cell Carcinoma

• For clinical stage I disease, surgery alone is the standard-of-care and provides superior 5-year overall survival (71%) compared to perioperative chemotherapy (58%), neoadjuvant therapy (38%), or adjuvant therapy (52%) 2
• Despite 37% of clinical stage I patients being upstaged to pathologic stage II/III, adjuvant therapy offers a favorable rescue strategy with improved outcomes compared to preoperative treatment 2
• For pathologic stage I disease, surgery alone affords similar or improved survival versus multimodality therapy 2

Colorectal Signet Ring Cell Carcinoma

• Signet ring cell adenocarcinoma of the colon and rectum is defined as having >50% of tumor demonstrating signet-ring cell morphology and is associated with worse stage-for-stage survival relative to conventional adenocarcinoma 1
• There is a strong association with microsatellite instability and BRAF V600E mutation 1
• Standard oncologic resection principles apply with appropriate lymphadenectomy 1
• Adjuvant chemotherapy and radiation therapy follow standard colorectal cancer protocols based on stage 1

Rectal Signet Ring Cell Carcinoma Considerations

• For locally advanced rectal signet ring cell carcinoma, neither long course chemoradiation nor short course radiation with chemotherapy shows superiority, with both approaches demonstrating high treatment failure rates (33.9% and 25.8% respectively) 3
• The peritoneum is the commonest site of progression (59.4%), reflecting the aggressive biology of this disease 3
• Minimally invasive surgery shows no significant difference in outcomes compared to open surgery, with mean disease-free survival of 29 months for MIS versus 25.8 months for open approach 4

Bladder Signet Ring Cell Adenocarcinoma

• Radical cystectomy with pelvic lymphadenectomy is the standard of care for locally advanced bladder signet ring cell adenocarcinoma 5
• The procedure should include removal of the bladder, prostate, seminal vesicles, proximal vas deferens, and proximal urethra, with complete removal of the prostate essential in cases of prostate base infiltration 5
• Adjuvant chemotherapy should be strongly considered due to advanced local stage, poor differentiation, and signet ring cell histology, with platinum-based combination chemotherapy regimens typically recommended 5
• Adjuvant radiation therapy should be considered for locally advanced disease, prostate base infiltration, and high risk of local recurrence, with radiation doses of 45-50.4 Gy to the tumor bed and regional lymph nodes with boost to 66-70 Gy for areas of residual disease or positive margins 5
• Survival is poor with greater than 50% of patients dead within a year after diagnosis; exenterative procedures offer the only hope of palliation as irradiation and chemotherapy alone have not been effective 6

Urachal Signet Ring Cell Adenocarcinoma

• Partial cystectomy with en-bloc excision of the urachus and umbilicus is the surgical approach 7
• Local radiotherapy should be considered for positive surgical margins 7
• For metastatic disease, combination chemotherapy with methotrexate, vinblastine, adriamycin and cisplatinum may provide temporary response lasting approximately 8 months 7

Surveillance

• Regular surveillance with cystoscopy and imaging studies every 3-6 months for the first 2 years is recommended for bladder signet ring cell adenocarcinoma 5
• For gastric HDGC patients on surveillance, annual endoscopy should be performed with immediate prophylactic total gastrectomy if signet ring cell lesions are identified 1

Critical Pitfalls

• Avoid routine use of neoadjuvant therapy for clinical stage I gastric signet ring cell carcinoma, as surgery alone provides superior outcomes and adjuvant therapy serves as an effective rescue strategy for upstaged disease 2
• Do not consider endoscopic or limited gastric resection for HDGC treatment, as signet ring cell foci are multifocal and occur throughout the stomach 1
• Recognize that signet ring cell carcinoma has subepithelial infiltrative nature making diagnosis possible only late in disease course, requiring high index of suspicion 6