Pathological Downstaging and Survival Outcomes Associated with Neoadjuvant Chemotherapy for Variant Histology Muscle Invasive Bladder Cancer

Chakiryan, Nicholas H.; Jiang, Da David; Gillis, Kyle; Green, Elizabeth; Hajiran, Ali; Hugar, Lee A.; Zemp, Logan; Zhang, Jingsong; Jain, Rohit; Chahoud, Jad; Poch, Michael; Manley, Brandon J.; Li, Roger; Sexton, Wade J.; Gilbert, Scott M.

doi:10.1097/ju.0000000000001855

Cited by 21 publications

(14 citation statements)

References 19 publications

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“…Of those, 67% harbored non-organ-confined disease. To the best of our knowledge, this is the second largest study examining such patient population 13 . The majority of studies addressing SBC relied on small populations: from 15 to 40 patients [6][7][8][9][10] on series of comparable or even larger size than the current series.…”

Section: Discussionmentioning

confidence: 98%

“…Most studies addressing this topic are limited by small sample size (from 15 to 40 patients) [6][7][8][9][10] . Conversely, three existing large scale populationbased studies originating from the National Cancer Database (NCDB) (155, 304, and 501 patients), are all invariably limited by lack of information on cancer-specific mortality (CSM) [11][12][13] . This methodological shortfall critically undermines their observations, since an important proportion of non-metastatic SBC patients treated with RC, die of non-cancer-related causes.…”

Section: Introductionmentioning

confidence: 99%

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The effect of chemotherapy in sarcomatoid bladder cancer patients treated with radical cystectomy

Tappero

Sorce²,

Hoeh³

et al. 2022

CUAJ

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Introduction: Data about the role of chemotherapy in sarcomatoid bladder cancer (SBC) are limited. We addressed the effect of chemotherapy in non-metastatic SBC patients treated with radical cystectomy. Methods: Using the Surveillance, Epidemiology, and End Results database (2001–2018), we identified 331 patients with non-metastatic muscle-invasive or higher SBC (T2-4N0-3M0). Kaplan-Meier plots and Cox regression models tested cancer-specific mortality (CSM). Sample size and power analyses tested for power limitations. Results: Of 331 SBC patients, 129 (38.9%) were exposed to chemotherapy. The rate of organ-confined stage (T2N0M0) was 33% in both chemotherapy-exposed and chemotherapy-naive patients. In the overall cohort, median CSM-free survival was 84 months (interquartile range [IQR] 21–NA) vs. 26 months (IQR 17–84) in chemotherapy exposed vs. chemotherapy-naive patients, respectively. In multivariable Cox regression models, chemotherapy was associated with lower CSM, without reaching statistical significance (hazard ratio [HR] 0.72, confidence interval [CI] 0.51–1.01, p=0.054). In subgroup analyses, chemotherapy exposure in organ-confined (n=110) vs. non-organ-confined (n=221) patients, resulted in a HR of 0.51 (p=0.12) vs. 0.77 (p=0.17), respectively. Power analyses, based on two-sided =0.05, revealed values of 52%, 14%, and 43% in the entire population, organ-confined, and non-organ-confined subgroups, respectively. Conclusions: In non-metastatic SBC treated with RC, the association between chemotherapy and lower CSM is particularly strong in organ-confined stage. A substantially larger cohort would be required to confirm the statistical significance of the recorded protective effect of chemotherapy.

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

The effect of chemotherapy in sarcomatoid bladder cancer patients treated with radical cystectomy

Tappero

Sorce²,

Hoeh³

et al. 2022

CUAJ

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“…In summary, the data regarding response to systemic chemotherapy from single/multicenter observational studies is not robust and often conflicting. Other published literature such as a retrospective cohort of non-metastatic cases from the National Cancer Database (NCDB) show that use of NAC correlates with higher likelihood to achieve pathologic complete response or downstaging prior to RC, whereas patients who did not receive NAC had very low rates of pCR (<6%) and downstaging (<10%) for all histologic variants (65).…”

Section: Glandular Differentiationmentioning

confidence: 99%

“…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). It was suggested that these patients may appear not benefit from NAC, despite significant pathological downstaging, because of generally more favorable outcomes.…”

Section: Glandular Differentiationmentioning

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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“…There were 14 studies evaluating the role of NAC for VH (8,10,11,(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27). Six were populations-based studies, seven studies came from different centers, and one study was based on both center and SEER.…”

Section: Study Selection and Characteristicsmentioning

confidence: 99%

Neoadjuvant and Adjuvant Chemotherapy for Variant Histology Bladder Cancers: A Systematic Review and Meta-Analysis

Zhu

Xiao

et al. 2022

Front. Oncol.

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ContextTo improve the prognosis of variant histology (VH) bladder cancers, clinicians have used neoadjuvant chemotherapy (NAC) or adjuvant chemotherapy (AC) on the basis of radical cystectomy (RC). Despite some new data, the evidence remains mixed on their efficacy.ObjectiveTo update the current evidence on the role of NAC and AC for VH bladder cancers.Evidence AcquisitionWe searched for all studies investigating NAC or AC for bladder cancer patients with variant histology in PubMed, Embase, and the Cochrane Central Register of Controlled Trials up to December 2021. The primary end points were recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS).Evidence SynthesisWe identified 18 reports comprising a total of 10,192 patients in the NAC studies. In patients with VH, the use of NAC did improve CSS (hazard ratio [HR] 0.74, 95% confidence interval [CI] 0.55–0.99, p = 0.044), and OS (HR 0.74, 95% CI 0.66–0.84, p = 0.000), but not RFS (HR 1.15, 95% CI 0.56–2.33, p = 0.706). Subgroup analyses demonstrated that receiving NAC was associated with better OS in sarcomatoid VH (HR 0.67, 95% CI 0.54–0.83, p = 0.000) and neuroendocrine VH (HR 0.54, 95% CI 0.43–0.68, p = 0.000). For AC, we identified eight reports comprising a total of 3254 patients. There was a benefit in CSS (HR 0.61, 95% CI 0.43–0.87, p = 0.006) and OS (HR 0.76, 95% CI 0.60–0.98, p = 0.032). Subgroup analyses demonstrated that only neuroendocrine VH had better CSS (HR 0.29, 95% CI 0.13–0.67, p = 0.174) when receiving AC.ConclusionsNAC or AC for VH bladder cancers confers an OS and CSS benefit compared with RC alone. For NAC, the benefit was independently observed in the sarcomatoid and neuroendocrine subgroups. As for AC, only neuroendocrine subgroups improved CSS.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42021289487.

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Pathological Downstaging and Survival Outcomes Associated with Neoadjuvant Chemotherapy for Variant Histology Muscle Invasive Bladder Cancer

Cited by 21 publications

References 19 publications

The effect of chemotherapy in sarcomatoid bladder cancer patients treated with radical cystectomy

The effect of chemotherapy in sarcomatoid bladder cancer patients treated with radical cystectomy

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

Neoadjuvant and Adjuvant Chemotherapy for Variant Histology Bladder Cancers: A Systematic Review and Meta-Analysis

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