Neoadjuvant chemotherapy–related histologic changes in radical cystectomy: assessment accuracy and prediction of response

Wang, Hui Jun; Solanki, Shraddha; Traboulsi, Samer L.; Kassouf, Wassim; Brimo, Fadi

doi:10.1016/j.humpath.2016.02.011

Cited by 13 publications

(22 citation statements)

References 19 publications

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“…While scoring was performed away from the TUR site, it may be that unlike other organs, there is an inherent increase in the number of granulocytes secondary to diagnostic bladder sampling irrespective of the host inflammatory response to the carcinoma. Conversely, aggregates of macrophages are not a frequent H&E finding in the bladder outside the setting of neoadjuvant chemotherapy (NAC),44 and indeed we only identified this histological feature in 18 of our cases, 7 of whom had NAC (exclusively foamy macrophages in NAC cases). While the scoring of central inflammation within the tumour did not show a statistically significant relationship with either RFS or DSS, a trend towards longer RFS and time to DSS was observed with high inflammation versus low inflammation (data not presented).…”

Section: Discussionmentioning

confidence: 50%

Tumour front inflammation and necrosis are independent prognostic predictors in high-grade urothelial carcinoma of the bladder

Hodgson

Xu²,

Satkunasivam

et al. 2017

J Clin Pathol

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AimsInflammation and necrosis have been associated with prognosis in multiple epithelial malignancies. Our objective was to evaluate inflammation and necrosis in a cohort of patients with high-grade urothelial carcinomas of the bladder to determine their association with pathological parameters and their prognostic effect on relapse-free and disease-specific survival.MethodsA retrospective cohort that underwent radical cystectomy for urothelial carcinomas (n=235) was evaluated for invasive front and central inflammation using the Klintrup-Makinen assessment method. Necrosis was scored using a four-point scale. The relationship of inflammation and necrosis with stage, nodal status, carcinoma in situ, tumour size, margin status and vascular space invasion and the impact on relapse-free and disease-specific survival were calculated using appropriate statistical tests.ResultsOn multivariate analysis, invasive front inflammation (p=0.003) and necrosis (p=0.000) were independent predictors of relapse-free survival. Both invasive front inflammation (p=0.009) and necrosis (p=0.002) again were independent predictors of disease-specific survival. For pathological features, low invasive front inflammation was associated with lymphovascular space invasion (p=0.008), a positive soft tissue margin (p=0.028) and carcinoma in situ (p=0.042). Necrosis was statistically associated with tumours >3â€‰cm in size (p=0.013) and carcinoma in situ (p<0.001).ConclusionsNecrosis and invasive front inflammation are additional histological variables with independent prognostic relevance in high-grade urothelial carcinoma of the bladder.

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Section: Discussionmentioning

confidence: 50%

Tumour front inflammation and necrosis are independent prognostic predictors in high-grade urothelial carcinoma of the bladder

Hodgson

Xu²,

Satkunasivam

et al. 2017

J Clin Pathol

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“…have shown that patients receiving NAC have better pathological endpoints at RC than those receiving TUR alone; in fact, Σ38% of the ‘pathological response’ (≤pT1pN0) post‐NAC can be attributed to TUR alone. Previous reports have shown a significant morphological overlap between the NAC effect and the TUR effect in RCs, highlighting the challenge of predicting more precisely whether the ‘pathological response’ in individual cases is attributable to NAC or TUR (or both) …”

Section: Discussionmentioning

confidence: 99%

“…The features considered to be specific to the NAC response, although rarely present, were hyalinisation of the bladder wall and fibrotic/necrotic changes in the lymph nodes. 20 This study was, however, limited by its observational nature and by the fact that it did not examine the relationship between histological features and clinical outcome.…”

Section: Introductionmentioning

confidence: 99%

Prognostic pathological factors in radical cystectomy after neoadjuvant chemotherapy

et al. 2018

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“…A number of chemotherapeutic agents, used either intravesically or systemically, may produce urothelial atypical changes that can be mistaken for urothelial CIS …”

Section: Chemotherapymentioning

confidence: 99%

“…The TRG correlated significantly with overall survival. More recently, Wang et al . compared cystectomy findings in patients with TURBT alone with TURBT with neoadjuvant chemotherapy, and found significant histological overlap between the two groups.…”

Section: Chemotherapymentioning

confidence: 99%

Iatrogenic changes in the urinary tract

et al. 2016

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A handful of therapeutic procedures are used to treat malignancies of the urinary tract, most frequently intravesical immunotherapy or chemotherapy, but also neoadjuvant systemic chemotherapy. These treatment modalities produce morphological changes in the urothelium that can be mistaken for carcinoma; in particular, these therapies frequently mimic urothelial carcinoma in situ (CIS) urothelial dysplasia or true invasive neoplasia. Drugs such as mitomycin C used after transurethral resection of bladder tumour to reduce recurrences, bacillus Calmette-Guérin (BCG) intravesical immunotherapy to treat high-risk non-muscle-invasive bladder cancer and urothelial CIS and platin-based systemic chemotherapy to improve postcystectomy disease-specific survival are examples of therapy-related atypia seen in the urinary tract. To complicate the pathologist's life, a number of systemic drugs in use to treat other diseases, such cyclophosphamide, used to treat some autoimmune disorders or certain haematological malignancies or, in the case of anaesthetics, ketamine, used increasingly as an illegal recreational drug, may produce similarly relevant atypical changes in the urothelium, and therefore need to be differentiated from intraepithelial neoplasia. Other less frequent procedures, such as photodynamic and laser therapy or the newer gene therapy to treat urothelial neoplasia, remain experimental. An immunohistochemical approach to reactive urothelium versus carcinoma in situ using p53, cytokeratin 20 and CD44 is also valid in the post-therapy setting. The pathologist should be aware of these novelties, as he or she plays a crucial role in evaluating treatment efficacy, but at the same time needs to avoid misdiagnosing secondary atypia as intraepithelial neoplasia.

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Neoadjuvant chemotherapy–related histologic changes in radical cystectomy: assessment accuracy and prediction of response

Cited by 13 publications

References 19 publications

Tumour front inflammation and necrosis are independent prognostic predictors in high-grade urothelial carcinoma of the bladder

Tumour front inflammation and necrosis are independent prognostic predictors in high-grade urothelial carcinoma of the bladder

Prognostic pathological factors in radical cystectomy after neoadjuvant chemotherapy

Iatrogenic changes in the urinary tract

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