Does neoadjuvant chemotherapy have therapeutic benefit for node-positive upper tract urothelial carcinoma? Results of a multi-center cohort study

Shigeta, Keisuke; Ogihara, Koichiro; Murakami, Tetsushi; Anno, Tadatsugu; Umeda, Kota; Izawa, Mizuki; Baba, Yoshihiko; Sanjo, Tansei; Shojo, Kazunori; Tanaka, Nobuyuki; Takeda, Toshikazu; Morita, Shinya; Kosaka, Takeo; Mizuno, Ryuichi; Arita, Yuki; Akita, Hirotaka; Jinzaki, Masahiro; Kikuchi, Eiji; Oya, Mototsugu

doi:10.1016/j.urolonc.2021.07.029

Cited by 16 publications

(12 citation statements)

References 29 publications

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“…23 Furthermore, cN+ disease substantially increases the likelihood of pN+ disease, explaining why cN+ patients could benefit from early systemic treatment. 24 Consequently, cN+ should be considered a solid argument to propose a neoadjuvant systemic therapy. Taking the results of this study into consideration when interpreting UTUC cN-staging results will aid in patient counseling and improve patient care.…”

Section: Discussionmentioning

confidence: 99%

Diagnostic Accuracy of Clinical Lymph Node Staging for Upper Tract Urothelial Cancer Patients: A Multicenter, Retrospective, Observational Study

et al. 2023

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Purpose:Treatment options for the management of upper tract urothelial cancer are based on accurate staging. However, the performance of conventional cross-sectional imaging for clinical lymph node staging (N-staging) remains poorly investigated. This study aims to evaluate the diagnostic accuracy of conventional cross-sectional imaging for upper tract urothelial cancer N-staging.Materials and Methods:This study was a multicenter, retrospective, observational study. We included 865 nonmetastatic (M0) upper tract urothelial cancer patients treated with curative intended surgery and lymph node dissection who had been staged with conventional cross-sectional imaging before surgery. We compared clinical (c) and pathological (p) N-staging results to evaluate the concordance of node-positive (N+) and node-negative (N0) disease and calculate cN-staging's diagnostic accuracy.Results:Conventional cross-sectional imaging categorized 750 patients cN0 and 115 cN+. Lymph node dissection categorized 641 patients pN0 and 224 pN+. The cN-stage was pathologically downstaged in 6.8% of patients, upstaged in 19%, and found concordant in 74%. The sensitivity and specificity of cN-staging were 25% (95% CI 20; 31) and 91% (95% CI 88; 93). Positive and negative likelihood ratios were 2.7 (95% CI 2.0; 3.8) and 0.83 (95% CI 0.76; 0.89). The area under the receiver operating characteristics curve (0.58, 95% CI 0.55; 0.61) revealed low diagnostic accuracy.Conclusions:Conventional cross-sectional imaging had low sensitivity in detecting upper tract urothelial cancer pN+ disease. However, cN+ increased the likelihood of pN+ by almost threefold. Thus, conventional cross-sectional imaging is a rule-in but not a rule-out test. Lymph node dissection should remain the standard during extirpative upper tract urothelial cancer surgery to obtain accurate N-staging. cN+ could be a strong argument for early systemic treatment.

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Section: Discussionmentioning

confidence: 99%

Diagnostic Accuracy of Clinical Lymph Node Staging for Upper Tract Urothelial Cancer Patients: A Multicenter, Retrospective, Observational Study

et al. 2023

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“…Regarding the argument of optimal timing of chemotherapy for cN + UTUC patients who were candidates for RNU, Shigeta et al recently published the results from a retrospective multicenter study [5]. The authors compared oncologic outcomes of presurgical induction chemotherapy followed by RNU versus RNU followed by postsurgical chemotherapy and reported that presurgical induction chemotherapy followed by RNU was signi cantly associated with better recurrence-free and cancer-speci c survival [5].…”

Section: Discussionmentioning

confidence: 99%

“…However, despite the changing treatment landscape owing to the development of perioperative systemic therapy, there is no guideline-endorsed treatment strategy for the management of clinical node-positive (cN+) UTUC patients [4]. RNU with perioperative systemic chemotherapy has been considered a reasonable treatment strategy in patients with cN + UTUC; however, the selection of optimal candidates who will most bene t from intensi ed therapy, including RNU, is of clinical importance [5].…”

Section: Introductionmentioning

confidence: 99%

C-reactive Protein is a Strong Prognostic Factor for Overall Survival in Clinically Node-positive Patients with Upper Tract Urothelial Carcinoma

Sasahara

Yanagisawa

Sugaya

et al. 2023

Preprint

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Background There is sparse evidence regarding optimal management and prognosticators for oncologic outcomes in patients with clinical node positive (cN+) upper tract urothelial carcinoma (UTUC). Methods We retrospectively analyzed the data from 105 UTUC patients with cN1-2M0 between June 2010 and June 2022 at multiple institutions affiliated with our university. At the time of diagnosis, all patients received standard-of-care treatment including radical nephroureterectomy (RNU), chemotherapy, and/or palliative care. We employed a Cox regression model to analyze the prognostic importance of various factors on overall survival (OS). Results Of 105 patients, 54 (51%) underwent RNU, while 51 (49%) did not. RNU was likely to be selected in younger and healthy patients, resulting in better median OS in patients who underwent RNU than in those who did not (42 months vs. 15 months, p < 0.001). Multivariable analysis among the entire cohort revealed that low G8 score (≤ 14) (hazard ratio [HR]: 2.20, 95% confidence interval [CI]: 1.15–4.23), elevated pretreatment C-reactive protein (CRP) (HR: 3.28, 95%CI: 1.59–6.76), and failure to perform RNU (HR: 2.27, 95%CI: 1.11–4.76) were independent prognostic factors for worse OS. In the subgroup analyses of cohorts who underwent RNU and those who did not, elevated pretreatment CRP was the only common independent prognostic factor for worse OS in cN + UTUC patients. Conclusions RNU seems to be a reasonable treatment option in cN + UTUC patients where applicable. Elevated pretreatment CRP appears to be a strong prognosticator of worse OS and may be helpful in optimizing candidate selection for intensified treatment in this setting.

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“…Given the high prevalence of lymphatic spread in UTUC, clinical node-positive (cNþ) UTUC patients should be considered for systemic platinum-based combination chemotherapy followed by RNU and LND; however, there is no guideline endorsement of this treatment strategy due to a lack of data to support this strategy that is used in urothelial cancer of the bladder [6,41]. Regarding the optimal timing of chemotherapy for cNþ UTUC patients who were candidates for RNU, Shigeta et al [42] recently published the results from a retrospective multicenter study comparing oncologic outcomes of systemic induction chemotherapy followed by RNU versus RNU followed by adjuvant chemotherapy. The authors reported that systemic induction chemotherapy followed by RNU was associated with significantly better DFS and CSS compared with RNU followed by adjuvant chemotherapy [42].…”

Section: Lymph Node Dissection In Clinical Node-positive Patientsmentioning

confidence: 99%

“…Regarding the optimal timing of chemotherapy for cNþ UTUC patients who were candidates for RNU, Shigeta et al [42] recently published the results from a retrospective multicenter study comparing oncologic outcomes of systemic induction chemotherapy followed by RNU versus RNU followed by adjuvant chemotherapy. The authors reported that systemic induction chemotherapy followed by RNU was associated with significantly better DFS and CSS compared with RNU followed by adjuvant chemotherapy [42]. However, although this data reflected clinical reality, there was severe selection bias that patients who did not respond to induction chemotherapy received second-line therapy (e.g.…”

Section: Lymph Node Dissection In Clinical Node-positive Patientsmentioning

confidence: 99%

Need for and extent of lymph node dissection for upper tract urothelial carcinoma: an updated review in 2023

Yanagisawa

Kawada

Deimling

et al. 2023

Current Opinion in Urology

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Purpose of reviewAlthough lymph node dissection (LND) during radical nephroureterectomy (RNU) is recommended for highrisk nonmetastatic upper tract urothelial carcinoma (UTUC), adherence to guidelines remains insufficient in clinical practice. Therefore, this review aims to comprehensively summarize the current evidence regarding the diagnostic, prognostic, and therapeutic impact of LND during RNU in UTUC patients. Recent findingsClinical nodal staging using conventional CT scan has low sensitivity (25%) and diagnostic accuracy [area under the curve (AUC): 0.58] in UTUC, suggesting the importance of LND for obtaining accurate Nstaging. Patients with pathological node-positive (pNþ) disease have poor disease-free survival (DFS), cancer-specific survival (CSS), and overall survival (OS) compared with those with pN0. In addition, population-based studies showed that patients who underwent LND improved CSS and OS than those who did not, even in patients who received adjuvant systemic therapy. The number of lymph nodes removed has also been shown to be associated with improved CSS and OS, even in pT0 patients. Template-based LND should be performed as the extent of lymph node is more important than the number of lymph nodes. Robot-assisted RNU may facilitate performing a meticulous LND compared with a laparoscopic approach. Postoperative complications such as lymphatic and/or chylous leakage are increased but adequately manageable. However, the current evidence is not supported by high-quality studies.

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Does neoadjuvant chemotherapy have therapeutic benefit for node-positive upper tract urothelial carcinoma? Results of a multi-center cohort study

Cited by 16 publications

References 29 publications

Diagnostic Accuracy of Clinical Lymph Node Staging for Upper Tract Urothelial Cancer Patients: A Multicenter, Retrospective, Observational Study

Diagnostic Accuracy of Clinical Lymph Node Staging for Upper Tract Urothelial Cancer Patients: A Multicenter, Retrospective, Observational Study

C-reactive Protein is a Strong Prognostic Factor for Overall Survival in Clinically Node-positive Patients with Upper Tract Urothelial Carcinoma

Need for and extent of lymph node dissection for upper tract urothelial carcinoma: an updated review in 2023

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