The impact of histological variants on outcomes after open radical cystectomy for muscle-invasive urothelial bladder cancer: results from a single tertiary referral centre

Naspro, Richard; Finati, Marco; Roscigno, Marco; Pellucchi, Federico; Croce, Giovanni La; Sodano, Mario; Manica, Michele; Chinaglia, D.; Pozzo, L. Da

doi:10.1007/s00345-020-03364-z

Cited by 16 publications

(19 citation statements)

References 29 publications

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“…Ten discussed NAC, one (12) discussed trimodal bladder preserving therapy (TMT) whereas one (4) discussed neoadjuvant immunotherapy. There were a total of 35 papers, 25 studies (5-7,9-11,14-32), then 10 studies (33)(34)(35)(36)(37)(38)(39)(40)(41)(42) reporting survival outcomes after cystectomy. Five of these studies (18,21,24,38,40) reported survival after RC with adjuvant chemotherapy.…”

Section: Actual Resultsmentioning

confidence: 99%

“…Recognize that in mixed histology or scenario wherein VH constitutes <50% of tumor specimen, it's presence regardless of percentage is a driver for poor outcomes Recognize glandular and squamous differentiation as having comparable response to NAC as conventional UC (5,13,14) Recognize the sarcomatoid differentiation as having demonstrated survival benefits with NAC (11) Recognize that after RC, micropapillay, plasmacytoid. nested and sarcomatoid variant histologies are associated with poor outcomes (16,18,19,35,37,38) validated as predictors of response to NAC in future trials.…”

Section: Discussionmentioning

confidence: 99%

“…Prognostic factors that impact response to NAC or survival outcomes in histologic variants of urothelial carcinoma after RC Certain histologic variants have been associated with worse survival outcomes after RC. Micropapillary, plasmacytoid, nested and sarcomatoid UC have been associated with worse survival outcomes compared to conventional UC and UC with squamous or glandular differentiation (16,18,19,35,37,38). Among these four histologic variants, survival benefit with NAC was demonstrated in sarcomatoid differentiation when controlling for other prognostic factors (11).…”

Section: Glandular 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: 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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“…Nevertheless, the presence of nested variant did not influence either 10-year recurrence-free survival (80% versus 83%; P = 0.46) or cancer-specific survival (41% versus 46%; P = 0.75), when compared with pure UC patients. Another recent cohort study [27] of 525 bladder cancer patients treated with open radical cystectomy at a single tertiary center reported a histological variant in 131 patients (25.0%). Their data suggested that the presence of a variant histology was associated with a more advanced and biologically aggressive malignancy, including a higher frequency of lymphovascular invasion and nodal disease at radical cystectomy.…”

Section: Discussionmentioning

confidence: 99%

Dissecting patterns of care in patients with variant histology of bladder cancer and lymph node invasion

Bandini¹,

Pederzoli²,

Necchi³

et al. 2021

Société Internationale D’Urologie Journal

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Objectives Lymph node invasion (LNI) is related to long-term survival in patients with muscle-invasive bladder cancer. However, in the case of variant histology (VH), data on pelvic lymph node dissection (PLND) and LNI are sparse. We described the pattern of care of PLND in patients with VHs of bladder cancer, exploring predictors of LNI. Methods Using the 2001–2016 SEER registry, 20 767 bladder cancer patients who underwent PLND were identified. Included histological variants were pure urothelial carcinoma (UC), micropapillary UC, sarcomatoid UC, lymphoepithelioma-like UC, adenocarcinoma, sarcoma, giant and spindle cell carcinoma, squamous cell carcinoma (SCC), and neuroendocrine tumor. Uni- and multivariable logistic regression analyses tested for LNI predictors. Cox regression was used to test for predictors of overall mortality (OM) among both LNI positive and LNI negative patients. Results Overall, 2464 (11.9%) harbored a VH. On multivariate analysis, only micropapillary UC was associated with higher risk (OR = 3.39) of LNI. This association was maintained when only the subset of patients treated without perioperative chemotherapy were analyzed (OR = 3.30). Similarly, higher T stage (T2 stage OR = 2.24; T3–4 stage OR = 9.44) and the use of chemotherapy (OR = 2.29) were associated with a higher risk of LNI. Among patients with LNI (5299, 25.5%), SCC (HR = 1.87), T3–4 stage (HR = 1.94), age at diagnosis (HR = 1.01) and geographic region (south) (HR = 1.22) were predictors of higher risk of OM. Conversely, chemotherapy (HR = 0.69) and number of removed LN (HR = −0.99) were associated with lower risk of OM. Finally, in a subgroup of patients without LNI, sarcomatoid UC (HR = 1.58) and giant and spindle cell carcinoma (HR = 1.83) were the only VH predictors of OM. Conclusions We described different patterns of care in patients with VHs of bladder cancer. Micropapillary UC was an independent risk factor for LNI. Among patients harboring LNI, those with SCC VH had higher OM compared to pure UC. Conversely, sarcomatoid UC and giant and spindle cell carcinoma were predictors of OM in patients without nodal involvement.

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“…Specifically, patients with pure urothelial carcinoma have ~11 times more chance to experience pathological complete response post-NAT compared to tumors with histological variants or mixed tumors. While pure urothelial carcinoma constitutes ~70% of cases of bladder cancer, the remaining cases contains a histologic variant or mixed histological features 15 . This intratumor heterogeneity is a significant hurdle to any clinical decision-making involving best choice of treatment for patients with UBC 19 .…”

Section: Current Precision Medicine-approaches For the Treatment Of Bmentioning

confidence: 99%

Emerging Roles of Urine-Derived Components for the Management of Bladder Cancer: One Man’s Trash is Another Man’s Treasure

Minkler¹,

Lucien²,

Kimber³

et al. 2020

Preprint

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Urinary bladder cancer (UBC) is the most common malignancy of the urinary tract in humans, with an estimated global prevalence of 1.1 million cases over 5 years1. Due to high rates of recurrence and resistance to chemotherapy, UBC is one of the most expensive cancers to treat, resulting in significant health care costs. There is, therefore, a critical need to develop innovative molecular and cellular tools to refine patient stratification and help predict response to treatment. Urine is an underused resource of biological components shed from bladder tumors, such as exfoliated cells and extracellular vesicles, that could serve as molecular fingerprints and provide valuable biological insights into tumor phenotype and mechanisms of resistance to chemotherapy. Additionally, characterization of urine-derived extracellular vesicles and cells could be used as reliable biomarkers for prediction of response to neoadjuvant therapy.

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The impact of histological variants on outcomes after open radical cystectomy for muscle-invasive urothelial bladder cancer: results from a single tertiary referral centre

Cited by 16 publications

References 29 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

Dissecting patterns of care in patients with variant histology of bladder cancer and lymph node invasion

Emerging Roles of Urine-Derived Components for the Management of Bladder Cancer: One Man’s Trash is Another Man’s Treasure

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