Is adjuvant treatment needed in T1 high-grade (T1 HG) N0 M0 lymphovascular invasion (LVI) positive upper tract urothelial carcinoma (UTUC) according to European Association of Urology (EAU) guidelines?

Adjuvant Treatment for T1 High-Grade N0 M0 LVI+ UTUC

According to the 2025 EAU guidelines, adjuvant platinum-based chemotherapy is recommended over neoadjuvant treatment for high-risk UTUC, and T1 high-grade disease with lymphovascular invasion (LVI+) qualifies as high-risk disease warranting consideration of adjuvant systemic therapy. 1

Risk Stratification and Treatment Rationale

• T1 high-grade UTUC with LVI+ represents high-risk disease that carries significant risk of metastatic recurrence and cancer-specific mortality 2
• LVI is an independent predictor of metastatic recurrence (subhazard ratio: 2.6) and correlates with 1.5-fold higher risk of recurrence and cancer-specific mortality 2
• The EAU explicitly states that adjuvant rather than neoadjuvant treatment is recommended for high-risk UTUC 1

Adjuvant Chemotherapy Recommendations

Platinum-based chemotherapy (PBC) is the preferred adjuvant treatment:

• Network meta-analysis demonstrates that adjuvant platinum-based chemotherapy yields superior oncological benefit over immune checkpoint inhibitors in patients treated with radical surgery for UTUC 1
• The EAU guidelines recommend adjuvant over neoadjuvant treatment despite evidence showing neoadjuvant chemotherapy benefits in high-risk disease 1

Specific regimen considerations:

• MVAC (methotrexate, vinblastine, doxorubicin, cisplatin) has shown superior outcomes in high-risk UTUC patients compared to gemcitabine-cisplatin or no adjuvant therapy 3
• In high-risk patients, MVAC achieved 1-year and 2-year recurrence-free survival rates of 71.4% and 47.9% respectively, significantly better than gemcitabine-cisplatin (48.2%) or no adjuvant therapy (53.4%) 3

Immunotherapy Considerations

Adjuvant immunotherapy has limited evidence in UTUC specifically:

• Adjuvant nivolumab improved disease-free survival in muscle-invasive urothelial carcinoma overall (20.8 vs 10.8 months), but subgroup analysis revealed that UTUC patients did not appear to benefit from adjuvant nivolumab 1
• Similarly, adjuvant pembrolizumab showed improved disease-free survival (29.6 vs 14.2 months) in the overall population, but UTUC patients (25% of study population) did not demonstrate benefit in subgroup analyses 1
• Nivolumab is EMA-approved for adjuvant treatment of muscle-invasive UC with PD-L1 expression >1% who decline or are unfit for adjuvant chemotherapy, but this is primarily based on bladder cancer data 1

Surgical Considerations

Lymph node dissection is not routinely indicated for T1 disease:

• Template-based LND is probably unnecessary in patients with Ta/T1 UTUC given the low risk of lymph node metastasis at lower tumor stages 1
• However, preoperative clinical staging is inaccurate, so template-based LND should be offered to all patients with high-risk disease scheduled for radical nephroureterectomy 1

Clinical Decision Algorithm

For T1 HG N0 M0 LVI+ UTUC after radical nephroureterectomy:

1. Confirm pathological high-risk features: T1 stage, high-grade histology, and presence of LVI 2
2. Assess renal function and cisplatin eligibility - this is critical as renal function declines post-nephroureterectomy 1
3. If cisplatin-eligible: Offer adjuvant platinum-based chemotherapy (MVAC preferred based on UTUC-specific data) 3
4. If cisplatin-ineligible and PD-L1 >1%: Consider adjuvant immunotherapy (nivolumab or pembrolizumab), though acknowledge limited UTUC-specific benefit 1
5. If cisplatin-ineligible and PD-L1 ≤1%: Close surveillance is recommended as no standard adjuvant therapy has proven benefit in this scenario 1

Important Caveats

• The evidence for adjuvant chemotherapy in UTUC is primarily from retrospective studies and meta-analyses, not randomized controlled trials 4, 3
• One large multicenter study found that adjuvant chemotherapy did not offer significant benefit to overall survival in high-risk UTUC (P >0.5), though this study had methodological limitations 4
• Positive surgical margins are an independent prognostic factor for recurrence, cancer-specific mortality, and overall mortality, which should influence adjuvant treatment decisions 4
• Metastatic recurrence occurs in over 25% of high-grade UTUC patients, with liver, bone, and multiple-site recurrences having particularly poor prognosis 2