Highlights
- •Fit elderly patients with high-risk UTUC may benefit equally from NAC and RNU as their younger counterparts
- •Cisplatin-based chemotherapy results in the highest pathologic response rates across both age groups
- •Elderly, cisplatin-ineligible patients, experienced the worst response rates after non-cisplantin-based NAC and might therefore benefit rather from immediate RNU
Abstract
Introduction
Although upper tract urothelial carcinoma (UTUC) is more common in the elderly, outcomes
of neoadjuvant chemotherapy (NAC) in this population have never been explored. The
objective of the study was to assess the impact of NAC on pathologic response and
oncological outcomes stratified by age.
Patients and Methods
This multicenter study included 164 patients treated with NAC and radical nephroureterectomy
(RNU) for clinically non-metastatic, high-risk UTUC. The cohort was stratified into
two groups according to median age. Patients received either cisplatin-based or non-cisplatin-based
chemotherapies. Pathologic responses were defined as pathologic objective response
(pOR; ≤ ypT1N0) and pathologic complete response (pCR; ypT0N0). Univariable and multivariable
logistic and Cox regression analyses were performed to identify predictors for pathologic
response and survival outcomes.
Results
The cohorts’ median age was 68 years with the elderly group (> 68 years) comprising
74 patients. Neoadjuvant chemotherapy included methotrexate-vinblastine-doxorubicin-cisplatin
(MVAC) in 66 (40%), gemcitabine cisplatin (GC) in 66 (40%) and non-cisplatin chemotherapy
in 32 patients (20%). Younger patients received more often MVAC (50% vs. 28%) while
elderly received more GC (34% vs. 47%) or non-cisplatin chemotherapy (16% vs. 24%)
(P = .02). Overall, pOR and pCR were similar across age groups (52% vs. 47%; P = .5 and 10% vs. 8%; P = .7). While GC and non-cisplatin chemotherapy showed a lower pCR of 5% and 3%, respectively,
MVAC revealed a pCR of 17% (P = .03) and was independently associated with a higher pCR (OR 4.31; P = .03). Kaplan-Meier analysis showed no difference in recurrence-free and cancer-specific
survival, whereas a lower rate was seen in overall survival for the elderly.
Conclusion
Elderly patients with high-risk UTUC eligible for cisplatin-based NAC prior to RNU
may benefit from this multimodal therapy equally as their younger counterparts. Cisplatin-ineligible
patients undergoing non-cisplatin-based NAC appeared to have lower response rates
and should be considered for immediate RNU.
Keywords
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References
- European Association of Urology Guidelines on upper urinary tract urothelial carcinoma: 2020 update.Eur Urol. 2021; 79: 62-79
- Epidemiology, diagnosis, preoperative evaluation and prognostic assessment of upper-tract urothelial carcinoma (UTUC).World J Urol. 2017; 35: 379-387
- Management of bladder cancer in older patients: position paper of a SIOG Task Force.J Geriatr Oncol. 2020; 11: 1043-1053
- Bladder cancer in the elderly.Urol Oncol. 2009; 27: 653-667
- The effect of age and gender on bladder cancer: a critical review of the literature.BJU Int. 2010; 105: 300-308
- Neoadjuvant and adjuvant chemotherapy for upper tract urothelial carcinoma: a 2020 systematic review and meta-analysis, and future perspectives on systemic therapy.Eur Urol. 2020; 79: 635-654
- Adjuvant chemotherapy in upper tract urothelial carcinoma (the POUT trial): a phase 3, open-label, randomised controlled trial.Lancet. 2020; 395: 1268-1277
- Tumor markers in prostate cancer I: blood-based markers.Acta Oncol. 2011; (50 Suppl 1(Suppl 1)): 61-75
- Efficacy of preoperative chemotherapy for high risk upper tract urothelial carcinoma.J Urol. 2020; 203: 1101-1108
- Preoperative predictors of renal function decline after radical nephroureterectomy for upper tract urothelial carcinoma.BJU Int. 2014; 114: 674-679
- Impact of renal function on eligibility for chemotherapy and survival in patients who have undergone radical nephro-ureterectomy.BJU Int. 2013; 112: 453-461
- Chronic kidney disease after nephrectomy in patients with small renal masses: a retrospective observational analysis.Eur Urol. 2012; 62: 696-703
- Advanced patient age is associated with inferior cancer-specific survival after radical nephroureterectomy.BJU Int. 2010; 105: 1672-1677
- Chronological age is not an independent predictor of clinical outcomes after radical nephroureterectomy.World J Urol. 2011; 29: 473-480
- Tumour architecture is an independent predictor of outcomes after nephroureterectomy: a multi-institutional analysis of 1363 patients.BJU Int. 2009; 103: 307-311
- Tumour necrosis is an indicator of aggressive biology in patients with urothelial carcinoma of the upper urinary tract.Eur Urol. 2010; 57: 575-581
- Combining imaging and ureteroscopy variables in a preoperative multivariable model for prediction of muscle-invasive and non-organ confined disease in patients with upper tract urothelial carcinoma.BJU Int. 2012; 109: 77-82
- Advanced age is associated with poorer bladder cancer-specific survival in patients treated with radical cystectomy.Eur Urol. 2007; 51 (discussion -8): 699-706
- Clinicians are poor raters of life-expectancy before radical prostatectomy or definitive radiotherapy for localized prostate cancer.BJU Int. 2007; 100: 1254-1258
- The impact of tumor multifocality on outcomes in patients treated with radical nephroureterectomy.Eur Urol. 2012; 61: 245-253
- The effect of tumor location on prognosis in patients treated with radical nephroureterectomy at Memorial Sloan-Kettering Cancer Center.Eur Urol. 2010; 58: 574-580
- Nephroureterectomy and segmental ureterectomy in the treatment of invasive upper tract urothelial carcinoma: a population-based study of 2299 patients.Eur J Cancer. 2009; 45: 3291-3297
- Impact of distal ureter management on oncologic outcomes following radical nephroureterectomy for upper tract urothelial carcinoma.Eur Urol. 2014; 65: 210-217
- Lymphadenectomy at the time of nephroureterectomy for upper tract urothelial cancer.Eur Urol. 2011; 60: 776-783
- Prediction of 90-day mortality after radical cystectomy for bladder cancer in a prospective European multicenter cohort.Eur Urol. 2014; 66: 156-163
- Death certificates are valid for the determination of cause of death in patients with upper and lower tract urothelial carcinoma.Eur Urol. 2012; 61: 854-855
- Treatment of patients with metastatic urothelial cancer "unfit" for Cisplatin-based chemotherapy.J Clin Oncol. 2011; 29: 2432-2438
- Greater risks of chemotherapy toxicity in elderly patients with cancer.J Support Oncol. 2003; 1 (4 Suppl 2): 18-24
- The effectiveness of off-protocol adjuvant chemotherapy for patients with urothelial carcinoma of the urinary bladder.Clin Cancer Res. 2010; 16: 4461-4467
- Efficacy of neoadjuvant and adjuvant chemotherapy for localized and locally advanced upper tract urothelial carcinoma: a systematic review and meta-analysis.Int J Clin Oncol. 2020; 25: 1037-1054
- Comparative effectiveness of neoadjuvant chemotherapy in bladder and upper urinary tract urothelial carcinoma.BJU Int. 2020; 127: 528-537
- Clinical and therapeutic factors associated with adverse pathological outcomes in clinically node-negative patients treated with neoadjuvant cisplatin-based chemotherapy and radical cystectomy.World J Urol. 2016; 34: 695-701
- Multicenter assessment of neoadjuvant chemotherapy for muscle-invasive bladder cancer.Eur Urol. 2015; 67: 241-249
- Changes in renal function following nephroureterectomy may affect the use of perioperative chemotherapy.Eur Urol. 2010; 58: 581-587
- Chronic kidney disease after nephroureterectomy for upper tract urothelial carcinoma and implications for the administration of perioperative chemotherapy.Cancer. 2010; 116: 2967-2973
Article Info
Publication History
Published online: January 11, 2022
Accepted:
January 4,
2022
Received in revised form:
December 11,
2021
Received:
May 12,
2021
Identification
Copyright
© 2022 Elsevier Inc. All rights reserved.
