What are the results of the POUT trial for patients with lymphovascular invasion (LVI) + upper tract urothelial carcinoma (UTUC) regarding adjuvant chemotherapy?

POUT Trial LVI+ Subgroup Results

Direct Answer to Your Question

The POUT trial did not publish separate subgroup results specifically for the LVI+ (lymphovascular invasion positive) population. The trial enrolled patients with pT2-T4 pN0-N3 M0 or pTany N1-3 M0 disease, which included patients with LVI as part of the high-risk criteria, but LVI-specific outcomes were not reported as a distinct subgroup analysis in the published results 1, 2.

What the POUT Trial Actually Reported

Overall Trial Results

• Disease-free survival benefit: Adjuvant chemotherapy showed HR 0.45 (95% CI 0.30-0.68; p=0.0001) at median 30-month follow-up 1
• Updated 5-year results: DFS was 62% versus 45% (HR 0.55,95% CI 0.38-0.80, p=0.001) at 65-month median follow-up 2
• Overall survival: 5-year OS was 66% versus 57% (HR 0.68,95% CI 0.46-1.00, p=0.049) 2

Inclusion Criteria (Which Encompassed LVI+ Patients)

• The trial included patients with pT2-T4 pN0-N3 M0 or pTany N1-3 M0 disease after nephroureterectomy 1, 2
• LVI+ patients were part of this high-risk cohort, but not analyzed separately 1

Why LVI+ Matters Clinically

LVI as an Independent Prognostic Factor

• LVI is present in approximately 19-20% of UTUC patients undergoing radical nephroureterectomy 3
• LVI independently predicts worse outcomes: 5-year RFS of 45.1% versus 79.3% without LVI (p<0.0001) 3
• LVI independently predicts CSS: HR 5.9 (p<0.0001) for cancer-specific survival 3
• Even in pN0/Nx disease, LVI remains prognostic: HR 2.1 for RFS and HR 2.3 for CSS (both p<0.001) 3

Clinical Implications for LVI+ Patients

• Adjuvant chemotherapy improves outcomes in high-risk UTUC (which includes LVI+ patients): propensity-matched analysis showed 5-year CSS of 69.0% with adjuvant chemotherapy versus 58.9% with surgery alone (p=0.030) 4
• LVI+ patients should be considered for adjuvant therapy based on their high-risk status 3

Where to Find POUT Trial Results

Primary Publication

• Lancet 2020: Initial results with primary endpoint (DFS) analysis 1
• Journal of Clinical Oncology 2024: Updated final results with mature OS data 2

Access Links

You can access these publications through:

• PubMed (search "POUT trial upper tract urothelial")
• ClinicalTrials.gov registry: NCT01993979 1
• Direct journal websites (Lancet and JCO)

Current Guideline Recommendations for LVI+ UTUC

Adjuvant platinum-based chemotherapy is recommended for all high-risk UTUC patients, including those with LVI+, based on POUT trial evidence 5, 6.

Specific Recommendations

• Cisplatin-based chemotherapy preferred: Gemcitabine-cisplatin regimen for cisplatin-eligible patients 5, 6
• Carboplatin-based chemotherapy NOT recommended: Due to insufficient evidence from POUT subgroup analysis 5
• Timing: Initiate within 90 days of nephroureterectomy 1, 6

Common Pitfall

Do not wait for LVI-specific subgroup data to make treatment decisions. The POUT trial demonstrated clear benefit for the entire high-risk population (which includes LVI+ patients), and LVI is an established independent adverse prognostic factor that warrants adjuvant therapy 6, 3.