Bladder Cancer – Variant

Histology

Michael Poch, MD

Assistant Member

Moffitt Cancer Center

Frontiers in Urologic Oncology

August 20th

VARIANT HISOTOLOGY VS

DIVERGENT DIFFERENTIATION

Variant Histology

Micropapillary

Nested

Plasmacytoid

Sarcomatoid

Divergent Histology

Squamous

Glandular

Shah et al urologic oncology 2013

Under-recognized!

• 45% are under-recognized in community

practice

– Lymphoepitheloid (100%, n=1)

– Plasmacytoid (100%, n=1)

– Nested (87%, 7)

– Micropapillary (80%. 10)

– Small Cell (44%, 7)

Under-recognized!

Non-Muscle Invasive Disease

1.Do variant histology tumors respond to BCG?

2. Is there a higher risk of upstaging?

Shift in management?

Shapur et al

144 pure urothelial

22 variant

Resected to T0

Recurrence free survival ~ 70%

similar between both groups

1.Do variant histology tumors

respond to BCG?

Shapur Rare Tumors 2011

2. Is there a higher risk of upstaging?

• Upstaging:

– Weizer et al risk factors for upstaging in 97 tumors

Mixed histology, urethral involvement, muscularis mucosa

Lymph Node +

– Domanowska et al

Upstaging: LN+

Domanowska et al Human Pathology 2007

Upstaging: LN+

Rice et al Urologic Oncology 2015

Upstaging; Extravesical Dz

Wasco et al Urology 2007

Upstaging

Rice et al Urologic Oncology 2015

Non-Muscle Invasive Disease

1.Do variant histology tumors respond to BCG?

*Unknown*

1. Is there a higher risk of upstaging?

*Yes*

Shift in management?

Early Cystectomy Should Be Considered/Offered

Micropapillary

First described 1992 - 18 patients (8 lymph node +)

•Associated with lymphovascular invasion, CIS and poor prognosis

•Compared to other aberrant histologies typically presents with lower stage disease

Non - muscle invasive TCC

Male to female 13:1

Overall Survival

•5 years - 61%

•10 years - 25%

Cancer Specific Survival

•5 years - 64%

•10 years - 26%

Micropapillary TCC •Initial cystectomy compared to BCG followed

by cystectomy

•5 yr CSS 72% vs 60%

Text

• Patients that delayed

cystectomy had

higher incidence of

>pT2 tumors and

node positive

disease

• 67% had

progression

• 22% mets

1

8

Micropapillary TCC MSKCC Experience

Recurrence Overall Survival

Nested Variant

Linder et al J Urology 2012

• 52 Nested bladder cancer patients

compared to 103 matched pure urothelial

• 10 year local RFS 77 % vs 75%

• 10 year distant met RFS 45% vs 51%

• CSS and OS were similar

Nested Variant

Linder et al J Urology 2012

Nested Variant

Linder et al J Urology 2012

• 30 Plasmacytoid patients compared to 278

Non-Variant Histology

• Higher Stage 74% vs 40%

• Higher N + disease 70% vs 25%

• Higher Margin + disease 40% vs 10%

Plasmacytoid

Kaimakliotis et al Urologic Oncology 2014c

Plasmacytoid

Kaimakliotis et al Urologic Oncology 2014c

Plasmacytoid

Kaimakliotis et al Urologic Oncology 2014c

• Dayyani et al

– High incidence of peritoneal mets

– 53% Response to NAC

Plasmacytoid

Dayyani et al J Urology 2013

Sarcomatoid

Data extremely limited

Wang et al Sarcoma 2010

Glandular & Squamous

Kim et al Journal of Urology 2012

Response To NAC

• Zargar et al 2016 Clin Gen Can

– Similar CR response from HV (25%) to to PUR (21%)

• Shen et al

– % of Variant Δ’s

Conclusions

• T1 patients should be offered early

cystectomy

– Particulary plasmacytoid, micropapillary,

sarcomatoid

• Less clear glandular, squamous

• At cystectomy patients tend to have worse

prognosis

• Response to neoadjuvant chemotherapy

needs to be sorted out

Thank you

• Questions