Intravesical seeding of upper urinary tract urothelial carcinoma cells during nephroureterectomy: an exploratory analysis from the THPMG trial.

Abstract

OBJECTIVE:

The Pirarubicin Monotherapy Study Group trial was a randomized Phase II study that evaluated the efficacy of intravesical instillation of pirarubicin in the prevention of bladder recurrence after nephroureterectomy for upper urinary tract urothelial carcinoma. This study conducted further analysis of the Pirarubicin Monotherapy Study Group cohort, focusing on intravesical seeding of cancer cells.

METHODS:

Using the data from the Pirarubicin Monotherapy Study Group trial, bladder recurrence-free survival rates and factors associated with bladder recurrence in the control group were analyzed.

RESULTS:

Of 36 patients in the control group, 14 with positive urine cytology had more frequent recurrence when compared with the 22 patients with negative cytology (P = 0.004). Based on the multivariate analysis in the control group, voided urine cytology was an independent predictive factor of bladder recurrence (hazard ratio, 5.54; 95% confidence interval 1.12-27.5; P = 0.036). Of 72 patients in the Pirarubicin Monotherapy Study Group trial, 31 had positive urine cytology. Among the 31 patients, 17 patients who received pirarubicin instillation had fewer recurrences when compared with 14 patients who received control treatment (P = 0.0001). On multivariate analysis, pirarubicin instillation was an independent predictor of better recurrence-free survival rates in the patients with positive urine cytology (hazard ratio, 0.02; 95% confidence interval, 0.00-0.53; P = 0.018). Of 21 patients with bladder recurrence, 17 had recurrent tumor around cystotomy or in the bladder neck compromised by the urethral catheter, supporting the notion that tumor cells seeded in the injured urothelium.

CONCLUSIONS:

Intravesical instillation of pirarubicin immediately after nephroureterectomy significantly reduced the bladder recurrence rate in patients with positive voided urine cytology. The results suggest that intravesical seeding of upper urinary tract urothelial carcinoma occurs during nephroureterectomy.

• Authors: Akihiro Ito, Ichiro Shintaku, Makoto Satoh, Naomasa Ioritani, Tatsuo Tochigi, Isao Numata, Takashige Namima, Koichi Kambe, Atsushi Kyan, Seiji Ueno, Shinnosuke Katoh, Hisanobu Adachi, Shinichi Yamashita, Takuhiro Yamaguchi, Yoichi Arai, Tohoku Urological EBM Study Group
• Journal: Japanese journal of clinical oncology (Jpn J Clin Oncol) Vol. 43 Issue 11 Pg. 1139-44 (Nov 2013) ISSN: 1465-3621 [Electronic] England
• PMID: 24006504 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Doxorubicin
• pirarubicin

Topics

• Administration, Intravesical
• Adult
• Aged
• Antineoplastic Agents (administration & dosage, therapeutic use)
• Carcinoma, Transitional Cell (drug therapy)
• Doxorubicin (administration & dosage, analogs & derivatives, therapeutic use)
• Female
• Humans
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Neoplasm Recurrence, Local (prevention & control)
• Neoplasm Seeding
• Nephrectomy (methods)
• Odds Ratio
• Risk Assessment
• Risk Factors
• Secondary Prevention (methods)
• Ureter (surgery)
• Urinary Bladder Neoplasms (etiology, prevention & control)
• Urine (cytology)
• Urologic Neoplasms (drug therapy)