Open Access

Evaluation of the Extent of Variant Histology in Urothelial Carcinoma as a Predictive Marker of Clinical Outcomes After Radical Cystectomy


1Department of Urology, School of Medicine,University of Occupational and Environmental Health, Kitakyushu, Japan

2Department of Pathology, Field of Oncology,Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan

3Department of Urology, Wakamatsu Hospital of the University of Occupational and Environmental Health,Kitakyushu, Japan

Cancer Diagnosis & Prognosis Sep-Oct; 1(4): 345-351 DOI: 10.21873/cdp.10046
Received 19 June 2021 | Revised 22 March 2023 | Accepted 12 July 2021
Corresponding author
Akinori Minato, Department of Urology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan. Tel: +81 936917446, Fax: +81 936038724


Background/Aim: This study investigated the impact of the extent of variant histology (VH) on the prognosis of patients with bladder cancer (BC). Patients and Methods: We retrospectively evaluated consecutive patients with muscle-invasive BC who were treated with radical cystectomy (RC) at our institution between 2005 and 2018. Recurrence-free survival (RFS) and overall survival (OS) rates were evaluated using Kaplan–Meier analysis and Cox regression. Results: We identified 103 and 47 patients with pure urothelial carcinoma (UC) and a VH in UC, respectively. At the cutoff of 80%, univariate analysis identified significant differences in RFS (p=0.046) and OS (p=0.038) between patients with ≥80% VH (n=21) and those with <80% VH (n=26). Multivariate analysis revealed that the presence of ≥80% VH was significantly associated with RFS and OS. Conclusion: The presence of ≥80% VH in UC could be an independent predictor of recurrence and mortality after RC.
Keywords: Urothelial carcinoma, variant histology, bladder cancer, radical cystectomy, prognosis

Bladder cancer (BC) is a common malignancy of the genitourinary system. According to Global Cancer Incidence, Mortality and Prevalence estimates, 549,000 new cases of BC and 199,000 deaths occurred worldwide in 2018 (1). Pure urothelial carcinoma (UC) is the predominant histology of BC; however, variant histologies (VHs) in UC are frequently observed in muscle-invasive BC (MIBC). Morphological diversity is common in UC, accounting for approximately 33% of surgical specimens in radical cystectomy (RC) (2). The opportunities for the treatment of VHs in UC are thus relatively increased.

Several studies have suggested that patients with variant histology (VH) have poorer survival outcomes compared with those with pure UC treated with RC (3-6), but others have reported similar survival rates for patients with pure UC and those with VH based on univariate analysis (7-9). Research controlling for the effects of clinicopathologic characteristics has shown that the presence of a VH in UC is not an independent predictor of mortality (10,11). However, these studies mainly focused on the prognostic value of the presence of VHs and were thus limited by their lack of adjustment for the extent of the VH. In daily practice, the proportion of the extent of the VH varies per case.

Soave et al. (12) reported an association between the extent of the VH and survival outcomes in an RC cohort. They did not find a prognostic benefit in stratifying patients by the extent of the VH (<70% or ≥70%). Nevertheless, the effect of the extent of the VH in MIBC has rarely been reported, and its impact on prognosis has yet to be fully elucidated. Evidence of the implication of this parameter’s survival prediction currently does not exist (2,7,12). Therefore, this study assessed the impact of the extent of the VH on oncological outcomes after RC.

Patients and Methods

Patient population. We conducted a retrospective review of 172 consecutive patients with MIBC (T2-4aN0M0) who had undergone RC at the University of Occupational and Environmental Health (UOEH; Kitakyushu, Japan) between March 2005 and September 2018. Only patients who had histologically confirmed pure UC or UC with a VH were included. Patients with such pure VHs as squamous cell carcinoma and adenocarcinoma as well as those without residual were excluded from the study, resulting in a total of 150 patients in the analysis. All the intended procedures in the present study were approved by the UOEH Institutional Review Board (approval no. H28-047).

Patient management. Patients underwent a routine precystectomy assessment, including physical examination, laboratory tests, confirmation of muscular invasion by transurethral resection of the bladder tumour, chest-abdominal-pelvic computed tomography (CT) scan and bone scintigraphy. All of them underwent RC, pelvic lymphadenectomy and urinary diversion. Tumour stage and nodal status were assigned according to the tumour, lymph nodes and metastasis (TNM) staging system (13).

The presence of VHs was re-reviewed in RC specimens by a dedicated genitourinary pathologist who was blinded to the clinical outcomes. Patients were classified as demonstrating a VH if they presented with UC combined with any morphological diversity in the RC specimens (14). VH subtypes were classified as per the World Health Organization Classification of Tumors (2). Each section was first scanned at low power for all tumoural fields (original magnification ×40) using conventional UC and VH subtypes to account for the heterogeneity of distribution. The extent of the VH was assessed by a meticulous workup of each slide via measurement of the proportion of the area it occupies in the whole lesion.

Prognostic assessment. Postoperative follow up examinations consisted of physical examinations, laboratory tests and CT scans, which were conducted every 6 months until the fifth year and annually thereafter. When symptoms appeared, the appropriate additional examinations were conducted. Disease recurrence was confirmed when local failure in the pelvic site, the presence of regional lymph nodes or distant metastasis, was detected. The recurrence-free survival (RFS) duration was calculated from the date of RC to the date of the first clinical recurrence or death due to any cause, or to the last follow up if the patient had no known recurrence. The overall survival (OS) duration was calculated from the date of RC to the date of death due to any cause, or to the date of the last follow up if the patient was alive. In addition, follow up information was obtained through the medical records of our institute or local hospitals. For patients whose medical records did not include follow up data, information was obtained through telephone contact.

Statistical analysis. All statistical analyses were performed using EZR ver.1.40 (Easy R, Vienna, Austria), which is a graphical user interface for R (The R Foundation for Statistical Computing). The Fisher exact test and χ2 test were used to examine associations between categorical variables, whereas the Mann–Whitney U-test was used to compare continuous variables. RFS and OS were estimated using the Kaplan–Meier method and the log-rank test. Univariable and multivariable Cox proportional hazards models assessed time to recurrence and mortality. p-Value <0.05 was considered statistically significant.


Clinicopathologic characteristics of histologic subtypes. Of the 150 patients, 103 (68.7%) had pure UC and 47 (31.3%) had a VH in UC. Squamous differentiation (16.7%) was the most common variant element, followed by glandular differentiation (4.7%) and micropapillary variant (4.0%) (Table I). The clinicopathologic characteristics of the patients stratified by pure UC and the presence of a VH are shown in Table II. The differences between the groups in terms of age, sex, age-adjusted Charlson comorbidity index score, and administration of neoadjuvant or adjuvant chemotherapy were not statistically significant. The presence of a VH was significantly associated with an advanced tumour stage and a higher rate of pathologic lymph node positive status.

Association of the extent of the VH with disease recurrence and mortality. The median follow-up time was 45 months [interquartile range (IQR)=23-96], during which 62 (41.3%) patients experienced recurrence and 55 (36.7%) died. The patients with a VH had poorer RFS and OS values compared with those with pure UC (Figure 1). The 3-year RFS rates of the pure UC and VH groups were 65.6% (median RFS, not reached) and 41.9% (median RFS, 14 months) (p=0.018), respectively; their corresponding 3-year OS rates were 74.9% (median OS, not reached) and 49.1% (median OS, 36 months) (p=0.012).

In the patients with a VH, the median extent of histologic subtypes in the whole lesion was 60% (IQR=20-80). The VH group was divided into two groups according to the proportion of histologic subtypes using the cut-off values of 20%, 40%, 60% and 80%. The RFS and OS rates of the groups, as estimated using univariate analysis, are presented in Table III. Comparisons of patients with ≥20% VH (n=37) vs. <20% VH (n=10), ≥40% VH (n=26) vs. <40% VH (n=21) and ≥60% VH (n=24) vs. <60% VH (n=23) revealed that the groups did not significantly differ in survival; the cut-off value of 80%, however, distinguished patients with a VH [≥80% (n=21) vs. <80% (n=26)] in terms of disease recurrence [hazard ratio (HR)=2.00; 95% confidence interval (CI)=1.09-4.18; p=0.046] and mortality (HR=2.28; 95%CI=1.07-5.33; p=0.038).

Kaplan–Meier curves assessed RFS and OS according to the following three categories: pure UC, <80% VH, and ≥80% VH (Figure 2). The outcomes between patients with pure UC and those with <80% VH did not exhibit any statistically significant difference. On the other hand, the patients with ≥80% VH had poorer RFS and OS compared with those with pure UC and those with <80% VH. The 3-year RFS rates of the <80% VH and ≥80% VH groups were 49.2% (median RFS, 37 months) and 32.7% (median RFS, 7 months) (p=0.047), respectively; their corresponding 3-year OS rates were 60.9% (median OS, not reached) and 34.6% (median OS, 19 months) (p=0.041).

The results of multivariate Cox proportional hazards regression analysis predicting RFS and OS after factors were adjusted for clinicopathologic characteristics are shown in Table IV. With regard to the extent of histologic subtypes in UC, ≥80% VH was identified as a significant independent predictor of disease recurrence (HR=2.08; 95%CI=1.08-3.99; p=0.028) and mortality (HR=2.27; 95%CI=1.15-4.49; p=0.019). In addition, advanced tumour stage and pathologic lymph node metastases were significantly associated with both survival outcomes.


To assess the influence of the extent of the VH on oncological outcomes, we conducted a pathologic re-review of RC specimens as well as a clinical investigation of patients treated with RC for pure UC or a VH in UC. The patients with ≥80% VH had poorer RFS and OS compared with those with pure UC and those with <80% VH. Moreover, the presence of ≥80% VH was significantly associated with worse oncological outcomes in multivariate analyses. The widespread presence of the VH was identified to reveal its survival value as a prognostic factor.

In general, UC is known to be associated with a variety of histologic differentiation markers (15). The increasing prevalence of VHs is largely due to improved pathologic recognition (16). In this study, we found that 31.3% of patients had a VH, with squamous differentiation, glandular differentiation, and micropapillary variant being common. The incidence rate of VHs in this study is similar to previously reported rates in patients treated with RC (2). In addition, the association between the presence of a VH and a higher rate of extravesical and lymph node positive disease is consistent with previous results (11,17).

We also found differences in survival between patients with pure UC and those with a VH. Although several studies previously assessed the impact of VHs at the time of RC, the results on survival outcomes are controversial (3-6,8-11). The dissension can be attributed to the studies’ lack of detailed pathologic features, including the percentage of the VH in the RC specimens. Many investigators have described the importance of assessing the influence of the extent of the VH on prognosis after RC (6,11,17-19). Although the recent meta-analysis by Mori et al. (18) showed that the presence of a VH was associated with worse RFS (pooled HR=1.32; 95%CI=1.20-1.45) and OS (pooled HR=1.44; 95%CI=1.26-1.65), it demonstrated that the extent of the VH had not been assessed by most studies. Therefore, a cut-off value for the extent of the VH that is associated with survival has yet to be established. Soave et al. (12) did not detect any difference in survival between tumours with <70% VH and those with ≥70% VH. In addition, a standard technique to help quantify the level of the VH within tumour lesions is currently not available (20). Although we assessed the extent of the VH subjectively, the results of our study suggest that its presence is a good prognostic factor by stratifying patients at the cut-off value of 80%.

In terms of each subtype of VH, Monn et al. (17) reported that the micropapillary and plasmacytoid variants were independently associated with the risk of mortality compared with pure UC, after adjusting for pathologic features. Moreover, we have previously demonstrated that squamous differentiation predicted poor OS after RC in multivariate analysis (21,22). However, we failed to identify the significance of ≥50% squamous differentiation in prognosis (22), which can be attributed to the extremely small sample size we used. By contrast, Mitra et al. (23) reported that ≥50% squamous differentiation was associated with significantly decreased rates of OS in univariate analysis. Another study on squamous differentiation and glandular differentiation by Kim et al. (7) indicated that the percentage categories of <30% vs. ≥30% did not differ in cancer-specific survival (CSS). Similarly, Wang et al. (24) did not detect any difference in CSS between the percentage categories of the micropapillary variant (10%, 10%-50% and ≥50%). To date, few studies have evaluated the impact of the extent of each variant, which renders the results thereof inconclusive. Although the impact of VHs on clinical outcomes may vary depending on the subtype, we considered all subtypes as one entity in analysing our study cohort. The limited number of patients with VH subtypes did not allow for a separate outcome analysis.

At the molecular level, MIBC is a heterogeneous disease that is characterised by genomic instability and a high mutation rate (25). Some investigators have demonstrated the importance of molecular subtype identification (26). Recently, Kamoun et al. (27) identified a consensus set of six molecular classes: luminal papillary, luminal nonspecified, luminal unstable, stroma-rich, basal/squamous, and neuroendocrine-like. VH subtypes are approximately represented within each consensus class; however, a discrepancy exists between each subtype of VH and these molecular classes. Warrick et al. (28) indicated that 39% of cases with a VH demonstrated intratumoural molecular heterogeneity in BC. Therefore, the concomitant presence of several mutational patterns may affect survival. Although we still cannot use molecular classification in the clinical setting, information on genomic alterations will change the biological recognition of UC with a VH in the future.

This study has several limitations, including its retrospective nonrandomised single-institutional design and small sample size. In addition, the treatment was not uniform, as some patients received RC alone, whereas others received RC with perioperative chemotherapy. The effects of neoadjuvant and adjuvant chemotherapy on outcomes in patients with a VH are currently unclear for MIBC (29-31) and require further exploration. However, despite these limitations, our results suggest that patients with ≥80% VH are at high risk of disease recurrence and short-term survival. Thus, the widespread presence of the VH may play a role in the aggressive behaviour of UC with MIBC treated with RC.

VHs are not always available in pathologic reports. Pathologists should report the proportion of the VH in UC lesions, which might help physicians predict poor survival outcomes after RC. We believe that our study provides a better understanding of the significance of VHs in terms of the biological behaviour of UC. Multi-institutional studies with larger cohorts and preferably using a prospective study design are warranted to further validate our results regarding the ideal threshold for VHs. In conclusion, the presence of ≥80% VH in UC could be an independent predictor of recurrence and mortality after RC.

Conflicts of Interest

The Authors declare that they have no competing interests in relation to this study.

Authors’ Contributions

AM: conceptualisation, investigation, data curation, formal analysis and writing of the original manuscript. HN: pathologic assessment. RM, KH and GY: investigation. RK and YH: data curation. IT and NF: supervision. All Authors discussed, verified and approved the final version of the manuscript.


1 Bray F Ferlay J Soerjomataram I Siegel RL Torre LA & Jemal A Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 68(6) 394 - 424 2018. PMID: 30207593. DOI: 10.3322/caac.21492
2 Humphrey PA Moch H Cubilla AL Ulbright TM & Reuter VE The 2016 WHO classification of tumours of the urinary system and male genital organs-part B: Prostate and bladder tumours. Eur Urol. 70(1) 106 - 119 2016. PMID: 26996659. DOI: 10.1016/j.eururo.2016.02.028
3 Kim HS Moon KC Jeong CW Kwak C Kim HH & Ku JH Histological variant as the significant predictor of survival in patients with lymph node positive urothelial carcinoma of the bladder. Sci Rep. 5 9626 2015. PMID: 25959144. DOI: 10.1038/srep09626
4 Shapur NK Katz R Pode D Shapiro A Yutkin V Pizov G Appelbaum L Zorn KC Duvdevani M Landau EH & Gofrit ON Is radical cystectomy mandatory in every patient with variant histology of bladder cancer. Rare Tumors. 3(2) e22 2011. PMID: 21769321. DOI: 10.4081/rt.2011.e22
5 Lee YJ Moon KC Jeong CW Kwak C Kim HH & Ku JH Impact of squamous and glandular differentiation on oncologic outcomes in upper and lower tract urothelial carcinoma. PLoS One. 9(9) e107027 2014. PMID: 25191845. DOI: 10.1371/journal.pone.0107027
6 Xylinas E Rink M Robinson BD Lotan Y Babjuk M Brisuda A Green DA Kluth LA Pycha A Fradet Y Faison T Lee RK Karakiewicz PI Zerbib M Scherr DS & Shariat SF Impact of histological variants on oncological outcomes of patients with urothelial carcinoma of the bladder treated with radical cystectomy. Eur J Cancer. 49(8) 1889 - 1897 2013. PMID: 23466126. DOI: 10.1016/j.ejca.2013.02.001
7 Kim SP Frank I Cheville JC Thompson RH Weight CJ Thapa P & Boorjian SA The impact of squamous and glandular differentiation on survival after radical cystectomy for urothelial carcinoma. J Urol. 188(2) 405 - 409 2012. PMID: 22704101. DOI: 10.1016/j.juro.2012.04.020
8 Scosyrev E Ely BW Messing EM Speights VO Grossman HB Wood DP de Vere White RW Vogelzang NJ Trump DL Natale RB Tangen CM Crawford ED & Thompson IM Do mixed histological features affect survival benefit from neoadjuvant platinum-based combination chemotherapy in patients with locally advanced bladder cancer? A secondary analysis of Southwest Oncology Group-Directed Intergroup Study (S8710). BJU Int. 108(5) 693 - 699 2011. PMID: 21105991. DOI: 10.1111/j.1464-410X.2010.09900.x
9 Zargar-Shoshtari K Sverrisson EF Sharma P Gupta S Poch MA Pow-Sang JM Spiess PE & Sexton WJ Clinical outcomes after neoadjuvant chemotherapy and radical cystectomy in the presence of urothelial carcinoma of the bladder with squamous or glandular differentiation. Clin Genitourin Cancer. 14(1) 82 - 88 2016. PMID: 26411593. DOI: 10.1016/j.clgc.2015.08.006
10 Marks P Gild P Soave A Janisch F Minner S Engel O Vetterlein MW Shariat SF Sauter G Dahlem R Fisch M & Rink M The impact of variant histological differentiation on extranodal extension and survival in node positive bladder cancer treated with radical cystectomy. Surg Oncol. 28 208 - 213 2019. PMID: 30851902. DOI: 10.1016/j.suronc.2019.01.008
11 Moschini M Shariat SF Lucianò R D’Andrea D Foerster B Abufaraj M Bandini M Dell’Oglio P Damiano R Salonia A Montorsi F Briganti A Colombo R & Gallina A Pure but not mixed histologic variants are associated with poor survival at radical cystectomy in bladder cancer patients. Clin Genitourin Cancer. 15(4) e603 - e607 2017. PMID: 28040422. DOI: 10.1016/j.clgc.2016.12.006
12 Soave A Schmidt S Dahlem R Minner S Engel O Kluth LA John LM Hansen J Schmid M Sauter G Shariat SF Fisch M & Rink M Does the extent of variant histology affect oncological outcomes in patients with urothelial carcinoma of the bladder treated with radical cystectomy?. Urol Oncol. 33(1) 21.e1 - 21.e9 2015. PMID: 25465301. DOI: 10.1016/j.urolonc.2014.10.013
13 Edge SB & Compton CC The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 17(6) 1471 - 1474 2010. PMID: 20180029. DOI: 10.1245/s10434-010-0985-4
14 Lopez-Beltran A & Cheng L Histologic variants of urothelial carcinoma: differential diagnosis and clinical implications. Hum Pathol. 37(11) 1371 - 1388 2006. PMID: 16949919. DOI: 10.1016/j.humpath.2006.05.009
15 Lobo N Shariat SF Guo CC Fernandez MI Kassouf W Choudhury A Gao J Williams SB Galsky MD Taylor JA 3rd Roupret M & Kamat AM What is the significance of variant histology in urothelial carcinoma. Eur Urol Focus. 6(4) 653 - 663 2020. PMID: 31530497. DOI: 10.1016/j.euf.2019.09.003
16 Mantica G Simonato A Du Plessis DE Maffezzini M De Rose AF van der Merwe A & Terrone C The pathologist’s role in the detection of rare variants of bladder cancer and analysis of the impact on incidence and type detection. Minerva Urol Nefrol. 70(6) 594 - 597 2018. PMID: 30203936. DOI: 10.23736/S0393-2249.18.03175-2
17 Monn MF Kaimakliotis HZ Pedrosa JA Cary KC Bihrle R Cheng L & Koch MO Contemporary bladder cancer: variant histology may be a significant driver of disease. Urol Oncol. 33(1) 18.e15 - 18.e20 2015. PMID: 25459358. DOI: 10.1016/j.urolonc.2014.10.001
18 Mori K Abufaraj M Mostafaei H Quhal F Karakiewicz PI Briganti A Kimura S Egawa S & Shariat SF A systematic review and meta-analysis of variant histology in urothelial carcinoma of the bladder treated with radical cystectomy. J Urol. 204(6) 1129 - 1140 2020. PMID: 32716694. DOI: 10.1097/JU.0000000000001305
19 Chen Q Li L Wang G Hu J Sun T & Fu B Do histological variants in urothelial carcinoma of the bladder portend poor prognosis? A systematic review and meta-analysis. Oncotarget. 8(29) 48263 - 48271 2017. PMID: 28525385. DOI: 10.18632/oncotarget.17593
20 Shah RB Montgomery JS Montie JE & Kunju LP Variant (divergent) histologic differentiation in urothelial carcinoma is under-recognized in community practice: impact of mandatory central pathology review at a large referral hospital. Urol Oncol. 31(8) 1650 - 1655 2013. PMID: 22608543. DOI: 10.1016/j.urolonc.2012.04.009
21 Minato A Fujimoto N & Kubo T Squamous differentiation predicts poor response to cisplatin-based chemotherapy and unfavorable prognosis in urothelial carcinoma of the urinary bladder. Clin Genitourin Cancer. 15(6) e1063 - e1067 2017. PMID: 28803791. DOI: 10.1016/j.clgc.2017.07.008
22 Minato A Noguchi H Tomisaki I Fukuda A Kubo T Nakayama T & Fujimoto N Clinical significance of squamous differentiation in urothelial carcinoma of the bladder. Cancer Control. 25(1) 1073274818800269 2018. PMID: 30213195. DOI: 10.1177/1073274818800269
23 Mitra AP Bartsch CC Bartsch G Jr Miranda G Skinner EC & Daneshmand S Does presence of squamous and glandular differentiation in urothelial carcinoma of the bladder at cystectomy portend poor prognosis? An intensive case-control analysis. Urol Oncol. 32(2) 117 - 127 2014. PMID: 23477878. DOI: 10.1016/j.urolonc.2012.08.017
24 Wang JK Boorjian SA Cheville JC Kim SP Tarrell RF Thapa P & Frank I Outcomes following radical cystectomy for micropapillary bladder cancer versus pure urothelial carcinoma: a matched cohort analysis. World J Urol. 30(6) 801 - 806 2012. PMID: 23132611. DOI: 10.1007/s00345-012-0976-0
25 Robertson AG Kim J Al-Ahmadie H Bellmunt J Guo G Cherniack AD Hinoue T Laird PW Hoadley KA Akbani R Castro MAA Gibb EA Kanchi RS Gordenin DA Shukla SA Sanchez-Vega F Hansel DE Czerniak BA Reuter VE Su X de Sa Carvalho B Chagas VS Mungall KL Sadeghi S Pedamallu CS Lu Y Klimczak LJ Zhang J Choo C Ojesina AI Bullman S Leraas KM Lichtenberg TM Wu CJ Schultz N Getz G Meyerson M Mills GB McConkey DJ TCGA Research Network Weinstein JN Kwiatkowski DJ & Lerner SP Comprehensive molecular characterization of muscle-invasive bladder cancer. Cell. 174(4) 1033 2018. PMID: 30096301. DOI: 10.1016/j.cell.2018.07.036
26 Moschini M D’Andrea D Korn S Irmak Y Soria F Compérat E & Shariat SF Characteristics and clinical significance of histological variants of bladder cancer. Nat Rev Urol. 14(11) 651 - 668 2017. PMID: 28895563. DOI: 10.1038/nrurol.2017.125
27 Kamoun A de Reyniès A Allory Y Sjödahl G Robertson AG Seiler R Hoadley KA Groeneveld CS Al-Ahmadie H Choi W Castro MAA Fontugne J Eriksson P Mo Q Kardos J Zlotta A Hartmann A Dinney CP Bellmunt J Powles T Malats N Chan KS Kim WY McConkey DJ Black PC Dyrskjøt L Höglund M Lerner SP Real FX Radvanyi F & Bladder Cancer Molecular Taxonomy Group A consensus molecular classification of muscle-invasive bladder cancer. Eur Urol. 77(4) 420 - 433 2020. PMID: 31563503. DOI: 10.1016/j.eururo.2019.09.006
28 Warrick JI Sjödahl G Kaag M Raman JD Merrill S Shuman L Chen G Walter V & DeGraff DJ Intratumoral heterogeneity of bladder cancer by molecular subtypes and histologic variants. Eur Urol. 75(1) 18 - 22 2019. PMID: 30266310. DOI: 10.1016/j.eururo.2018.09.003
29 Kaimakliotis HZ Monn MF Cho JS Pedrosa JA Hahn NM Albany C Gellhaus PT Cary KC Masterson TA Foster RS Bihrle R Cheng L & Koch MO Neoadjuvant chemotherapy in urothelial bladder cancer: impact of regimen and variant histology. Future Oncol. 12(15) 1795 - 1804 2016. PMID: 27255805. DOI: 10.2217/fon-2016-0056
30 Vetterlein MW Wankowicz SAM Seisen T Lander R Löppenberg B Chun FK Menon M Sun M Barletta JA Choueiri TK Bellmunt J Trinh QD & Preston MA Neoadjuvant chemotherapy prior to radical cystectomy for muscle-invasive bladder cancer with variant histology. Cancer. 123(22) 4346 - 4355 2017. PMID: 28743155. DOI: 10.1002/cncr.30907
31 Berg S D’Andrea D Vetterlein MW Cole AP Fletcher SA Krimphove MJ Marchese M Lipsitz SR Sonpavde G Noldus J Shariat SF Kibel AS Trinh QD & Mossanen M Impact of adjuvant chemotherapy in patients with adverse features and variant histology at radical cystectomy for muscle-invasive carcinoma of the bladder: Does histologic subtype matter. Cancer. 125(9) 1449 - 1458 2019. PMID: 30620387. DOI: 10.1002/cncr.31952