Pathological and Survival Outcomes Associated with Variant Histology Bladder Cancers Managed by Cystectomy with or without Neoadjuvant Chemotherapy

Hajiran, Ali; Azizi, Mounsif; Aydın, Ahmet; Zemp, Logan; Peyton, Charles C.; Dhillon, Jasreman; Nealon, Samantha W.; Reich, Richard R.; Cao, Biwei; Li, Roger; Manley, Brandon J.; Sexton, Wade J.; Gilbert, Scott M.

doi:10.1097/ju.0000000000001325

Cited by 33 publications

(31 citation statements)

References 28 publications

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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%

“…There is evidence of improved survival in patients with sarcomatoid differentiation receiving NAC compared to RC alone. (5,14) This may be an alternative therapeutic option in glandular and squamous differentiation, evidence from a single institutional study (12) Findings on the efficacy of neoadjuvant pembrolizumab are preliminary.…”

Section: Discussionmentioning

confidence: 99%

“…It is worth noting that some studies that reported no significant difference in survival outcomes between conventional UC and VH of UC had predominantly squamous and/glandular differentiation such as was reported in Sefik et al (32). Hajiran et al (14) was the only study to compare the survival benefit of NAC between the three groups of conventional UC, UC with VH and UC with variant differentiation (squamous or glandular); here survival benefit with NAC was only achieved in conventional UC and UC with VH. A possible explanation for this apparent lack of survival benefit for NAC in variant differentiation was offered by Chakiryan et al (65).…”

Section: Glandular Differentiationmentioning

confidence: 91%

“…NAC resulted in higher likelihood to achieve pCR, more than seen in patients who did not receive NAC (5,6) and higher incidence of downstaging (5). Three studies (5,13,14) reported that in comparison, the pathologic complete response rates to NAC were similar in conventional UC and UC with squamous differentiation while rates of pathologic downstaging was higher in UC with squamous differentiation (5,13). A single institutional study showed excellent rates of pathologic complete response with trimodal bladder preserving therapy as well (12).…”

Section: Squamous Cell Differentiationmentioning

confidence: 99%

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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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Section: Actual Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Glandular Differentiationmentioning

confidence: 91%

Section: Squamous Cell Differentiationmentioning

confidence: 99%

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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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“…Until recently, BCa treatment had seen little progress. For 30 years, clinicians offered the same, limited range of therapeutics to patients, and the 5-year survival rates were flat (7)(8)(9). Further analysis of the causes of death in patients with BCa showed that tumor-specific deaths account for a large proportion, but the proportion of non-tumor-specific deaths is also surprisingly high, especially heart-specific mortality (10).…”

Section: Introductionmentioning

confidence: 99%

Effects of radical cystectomy, radiotherapy, and chemotherapy on the risk of long-term heart-specific death in bladder cancer patients

Yang¹,

Li²,

Guo³

et al. 2021

Transl Androl Urol

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Background: At present, the low risk of bladder cancer (BCa)-specific death has allowed for investigation into treatment-related cardiotoxicity. To aid clinicians in selecting appropriate cardiovascular disease screening strategies and interventions, this study explored the heart-specific mortality and prognostic factors of patients with BCa after radical cystectomy (RC), radiotherapy (RT), or chemotherapy (CT), and compared their long-term heart-specific mortality with that of the general male population. Methods: We identified three different treatments for BCa patients from the Surveillance, Epidemiology, and End Results (SEER) database: RC, RT, and CT. Patients were included from 2000 to 2012 and followed through 2015. A cumulative mortality curve and competitive risk regression model were applied to evaluate the prognostic factors of heart-specific mortality, and standardized mortality ratios (SMRs) were calculated.Results: Of 39,500 men, 30.3%, 18.8%, and 50.9% received RC, RT, and CT, respectively. For patients with a survival period of less than 50 months, tumor-specific death exhibited a rapidly increasing trend, which subsequently flatlined. However, the rates heart-specific mortality and other causes exhibited a tendency to increase stably. The heart-specific and all-cause mortality rates of patients in any age group treated with the three abovementioned strategies were higher than those of the general population. The heart-specific mortality of patients with carcinoma in situ treated with RC and CT exceeded their all-cause mortality, while that of other tumor stages did not. The risks of heart-specific [sub-distribution hazard ratio (SHR) =1.38; 95% confidence interval (CI): 1.22-1.57] and tumor-specific (SHR =1.68; 95% CI: 1.60-1.77) deaths in patients who received RT were higher than those of patients who underwent CT. Conclusions:The risks of heart-specific and tumor-specific deaths in patients who received RT were higher than those of the RC and CT groups, especially in patients over 65 years of age who received RT.

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A nested variant of urothelial carcinoma of the urethra and urinary bladder: A case report and review of literature

Kermani

Kalantari

Feizabad

et al. 2023

Clinical Case Reports

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Nested variant of urothelial carcinoma (NV-UC) is an extremely rare cancer with a nonspecific presentation. It is usually identified at a late stage, which makes the treatment challenging. Herein we report the case of a 52-year-old woman with an advanced NV-UC treated by anterior exenteration after a poor response to neoadjuvant chemotherapy. One year after completion of adjuvant radiotherapy, the patient remains disease-free.

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Pathological and Survival Outcomes Associated with Variant Histology Bladder Cancers Managed by Cystectomy with or without Neoadjuvant Chemotherapy

Cited by 33 publications

References 28 publications

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

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

Effects of radical cystectomy, radiotherapy, and chemotherapy on the risk of long-term heart-specific death in bladder cancer patients

A nested variant of urothelial carcinoma of the urethra and urinary bladder: A case report and review of literature

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