Neoadjuvant Chemotherapy in Urothelial Bladder Cancer: Impact of Regimen and Variant Histology

Kaimakliotis, Hristos Z.; Monn, M. Francesca; Cho, Jane S.; Pedrosa, Jose A.; Hahn, Noah M.; Albany, Costantine; Gellhaus, Paul T.; Cary, K. Clint; Masterson, Timothy A.; Foster, Richard S.; Bihrle, Richard; Liu, Cheng; Koch, Michaël

doi:10.2217/fon-2016-0056

Cited by 11 publications

(15 citation statements)

References 32 publications

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“…In a subgroup analysis from the randomized controlled trial (RCT) SWOG 8710, patients with mixed histology (squamous or glandular) were seen to have a survival benefit with NAC (HR 0.46; 95% CI 0.25-0.87; p = 0.02) compared with primary RC [14]. These results are consistent with the findings of Kaimakliotis et al [15] who reported similar oncological outcomes of NAC for patients with pure urothelial bladder cancer (n = 54) and variant histology (n = 30), with the latter being mostly represented by squamous or glandular differentiation. The presence of squamous or glandular variants was associated with higher rates of pathological downstaging (OR 4.01; 95% CI 1.16-13.9) but similar OS when compared with pure urothelial carcinomas [16].…”

Section: Pathological Classificationsupporting

confidence: 85%

Predicting Response to Neoadjuvant Chemotherapy in Bladder Cancer

Motterle

Andrews

Morlacco

et al. 2020

European Urology Focus

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Section: Pathological Classificationsupporting

confidence: 85%

Predicting Response to Neoadjuvant Chemotherapy in Bladder Cancer

Motterle

Andrews

Morlacco

et al. 2020

European Urology Focus

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“…The presence of variant histology does not appear to compromise the efficacy of preoperative chemotherapy in patients with UC of squamous or glandular differentiation. 8 , 9 However, the utility of preoperative chemotherapy for patients with PUC remains poorly defined. Anti-programmed cell death 1 (anti-PD1)/programmed cell death ligand 1 (PDL1) immune checkpoint inhibitors (ICIs) are also used to treat patients with UC 10 – 13 and have an emerging role in preoperative therapy.…”

Section: Introductionmentioning

confidence: 99%

Natural history, response to systemic therapy, and genomic landscape of plasmacytoid urothelial carcinoma

et al. 2021

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Background Plasmacytoid urothelial carcinoma (PUC) is a rare, aggressive histologic variant of urothelial cancer characterised by a diffuse growth pattern and CDH1 mutation. We studied the efficacy of preoperative platinum-based chemotherapy in nonmetastatic PUC and immune checkpoint inhibitors (ICIs) in advanced PUC. Methods Cases of nonmetastatic PUC and advanced PUC treated with ICIs at our institution were identified. Outcomes were compared to those of a published cohort of patients with urothelial carcinoma not otherwise specified. Results We identified 81 patients with nonmetastatic PUC. Of the patients with localised disease who underwent neoadjuvant chemotherapy, pathologic complete response and downstaging rates were 12 and 21%, respectively. Pathologic downstaging was not associated with significant improvement in clinical outcomes. Up to 18% of localised disease and 28% of locally advanced cases had unresectable disease at the time of surgery. ICI-treated advanced PUC (N = 21) had progression-free and overall survival of 4.5 and 10.5 months, respectively, and a 38% response rate. FGFR3 and DNA damage response gene alterations were observed in 3 and 15% of cases, respectively. Conclusions PUC is associated with high disease burden and poor chemosensitivity. Increased awareness and recognition of this disease variant will allow for new treatment strategies.

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“…Pathologic complete response was reported in ten studies (4-6,8,10-14,36) while pathologic downstaging was reported in nine studies (4,5,7,8,10,11,(13)(14)(15). S u r v i v a l b e n e f i t w i t h N A C i n V H o f U C w a s demonstrated in two studies (5,14), and specifically with sarcomatoid differentiation (11) and squamous differentiation (6,9).…”

Section: Actual Resultsmentioning

confidence: 99%

Overview of histologic variants of urothelial carcinoma: current trends and narrative review on treatment outcomes

Ogbue

Haddad²,

Almassi³

et al. 2022

Transl Androl Urol

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Background and Objective: The histologic variants of urothelial carcinoma (UC) are tumors arising from within the urothelium in which some component of the tumor morphology is other than urothelial.They are underdiagnosed, aggressive and have varying pathologic response rates to systemic chemotherapy.There are no consensus guidelines on the use of systemic chemotherapy in variant histology (VH) of UC. We performed a contemporary review on pathologic response rates to neoadjuvant systemic therapy and survival outcomes following radical cystectomy in order to provide a rationale for clinical practice recommendations on the management of UC with VH.Methods: A PubMed literature search was conducted for all English articles from inception reporting either pathological response rates to neoadjuvant treatment or survival outcomes after radical cystectomy in non-metastatic VH of UC.Key Content and Findings: Neoadjuvant chemotherapy (NAC) prior to radical cystectomy was shown to be a beneficial treatment strategy in UC with VH. The micropapillary, plasmacytoid, nested and sarcomatoid histologic variants were associated with worse survival outcomes compared to conventional UC and UC with squamous or glandular differentiation despite initial downstaging with chemotherapy. There is evidence of improved survival in patients with sarcomatoid differentiation receiving NAC compared to RC alone. The major prognostic factors that affect survival outcomes in VH of UC include histologic variant subtype, patient age, presence of lymphovascular invasion, hydronephrosis, nodal metastasis and advanced T stage at diagnosis. Recent studies demonstrate that VH of UC are heterogenous tumors and responsiveness to NAC may be a function of the molecular subtypes present.Conclusions: Based on these findings, NAC to achieve pathologic downstaging prior to radical cystectomy is recommended for MIBC with VH. Biomarkers identified by molecular profiling with immunohistochemistry will need to be validated as predictors of response to NAC in future trials.

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Neoadjuvant Chemotherapy in Urothelial Bladder Cancer: Impact of Regimen and Variant Histology

Abstract: NACT was associated with improved survival, pCR and pDS. Furthermore, responses to NACT were not dependent on presence of VH.

Cited by 11 publications

References 32 publications

Predicting Response to Neoadjuvant Chemotherapy in Bladder Cancer

Predicting Response to Neoadjuvant Chemotherapy in Bladder Cancer

Natural history, response to systemic therapy, and genomic landscape of plasmacytoid urothelial carcinoma

Overview of histologic variants of urothelial carcinoma: current trends and narrative review on treatment outcomes

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