The researchers collected data from 9,436 patients with primary UTUC from the SEER database. Among these patients, 13.3% developed distant metastasis. The median age at diagnosis was 72 years, and 59.8% of patients were male. Fewer patients with distant metastases were treated with surgery and lymph node dissection than those without metastases. Instead, they were more likely to be treated with radiotherapy and chemotherapy. The following factors were associated with distant metastases: higher clinical T and N stages and larger tumor diameters. Lung metastasis (42.5%) was the most common location, while brain metastasis was the least common (2.5%). Among patients with metastasis, 1,047 cancer-specific deaths occurred (83%).
Most cases of metastasis were single-site specific metastasis (60.1%). In patients with single-site metastasis without surgical intervention, patients with distant lymph node metastases had the highest overall survival at one, three, and five years. They also had the longest median survival time (8 months). Patients with brain metastases exhibited the lowest rates. In contrast, patients with single metastases who had nephroureterectomy showed significantly improved overall survival rates at the three time points and improved median survival time. This was also observed among patients with multiple metastases. Univariate and multivariate logistic regressions highlighted the following factors as being significantly associated with metastasis at diagnosis: renal pelvis tumors, high-grade tumors, large tumor size (>4 cm), high T stage (T3, T4), and high N stage (N1, N2, N3). Strikingly, age above 80 years was negatively correlated with the probability of distant metastases. Researchers then analyzed predictors of metastasis for each site and found that the clinical N stage was a significant predictor across all sites. Renal pelvis cancer was an independent predictor of lung metastasis. Clinical T stage (T4) and age above 80 years were significantly associated with bone, liver, and brain metastases. With respect to survival outcomes, single distant lymph node metastases were associated with higher overall survival, cancer-specific survival, and median survival time relative to other types of single metastasis. However, the overall survival rate drops to almost zero at five years for all single-site metastases. Patients with multiple metastases exhibited a rapid decline in overall and cancer-specific survival in the first year. The survival rate at ten years is zero across all cases of single and multiple metastases. Surgical resection of the primary tumor and nephroureterectomy increased survival time among patients who developed any type of distant metastases in the short term. Chemotherapy was associated with better survival among patients with metastases.
The predictive factors identified in this study can also help guide clinicians with patient prognosis at initial diagnosis. The mechanisms behind many of these observations, such as the association between renal pelvic cancer and lung metastasis, will require further investigation. It should be noted that the SEER database only contains information about lung, bone, liver, brain, and distant lymph node metastases, but not other types of metastases. Moreover, researchers did not have access to details about the treatment sequence or complications.
Written by: Bishoy M. Faltas, MD, Director of Bladder Cancer Research, Englander Institute for Precision Medicine, Weill Cornell Medicine
References:
- Hu XH, Miao J, Qian L, Zhang DH, Wei HB. The predictors and surgical outcomes of different distant metastases patterns in upper tract urothelial carcinoma: A SEER-based study. Front Surg. 2022;9:1045831. Published 2022 Nov 4. doi:10.3389/fsurg.2022.1045831