Impact of High-risk Features and Effect of Neoadjuvant Chemotherapy in Urothelial Cancer Patients with Invasion into the Lamina Propria on Transurethral Resection in the Absence of Deep Muscle Invasion

Abstract

Background High-risk non–muscle-invasive bladder cancer (NMIBC) that invades into the lamina propria is frequently understaged and is associated with a risk of lymph node metastasis and death. Objective To identify high-risk features (HRFs) for NMIBC that may identify patients with poorer prognosis who may benefit from neoadjuvant chemotherapy (NAC) prior to radical cystectomy (RC). Design, setting, and participants We performed a single-center retrospective review of patients who underwent RC for NMIBC with invasion into the lamina propria between 1995 and 2013. HRFs included hydronephrosis, abnormal examination under anesthesia, lymphovascular invasion, or variant histology. Outcome measurements and statistical analysis Pathology at RC, and overall (OS) and disease-specific (DSS) survival were evaluated and analyzed by Fisher’s exact test, Student t test, Cox proportional hazards regression analysis, and the Kaplan–Meier method. Results and limitations We identified 336 patients with a median follow-up of 130 mo. Of these, 159 (47%) had no HRF, 140 (41.5%) had one HRF, and 37 (11%) had ≥2 HRFs. At RC, patients with ≥2 HRFs had a significantly higher rate of pathologic T stage upstaging and lymph node metastasis (p < 0.05). Median OS was 139 mo for those with no HRF, 127 mo for those with one HRF, and 56 mo for those with ≥2 HRF (p = 0.0057). HRFs are also associated with a decreased DSS (p = 0.0009). Patients with ≥2 HRFs (11/37) who received NAC showed improved OS (21% vs 55% 5-yr OS, p = 0.0353) and trended toward an improvement in DSS (25% vs 56% 5-yr OS, p = 0.0716) compared with RC alone. Conclusions The presence of ≥2 HRFs in NMIBC invading the lamina propria is associated with worse pathology at RC and a significant decrease in OS and DSS. NAC appears to provide benefit for these patients. Limitations include retrospective design and limited sample size. Patient summary The presence of high-risk features in urothelial cancer with invasion into the lamina propria has a worse prognosis that may be mitigated by neoadjuvant chemotherapy.

Treatment Outcomes of High-Risk Non-Muscle Invasive Bladder Cancer (HR-NMIBC) in Real-World Evidence (RWE) Studies: Systematic Literature Review (SLR)

“…16,17,19,[21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][40][41][42][43][44]46,49,51,54,56,57,[61][62][63]65,68,69,[72][73][74][75][76] BCG therapy was an inclusion criterion for some of these studies, which contributed to this high rate. In the remaining 18 studies (30%), the reported use of BCG instillations in HR-NMIBC patients ranged from 3% to 86%.- 18,20,39,45,47,48,50,52,…”

“…16,17,21,22,[24][25][26][27][28]31,[33][34][35][36][37]40,42,49,51,54,56,57,61,65,68,74,75,77 Among the remaining eight studies, rates of BCG induction therapy ranged from 29% to 95%. 20,45,47,52,59,63,77,78 The use of maintenance BCG in HR-NMIBC was reported in 31 studies, with rates being more variable than those seen with induction therapy. 16,17,[26][27][28][29]31,33,34,36,37,40,42,45,46,[49]…”

“…37,42,58 The use of re-TURBT in patients with HR-NMIBC was reported in 43 studies. 16,[18][19][20][21][22][23][27][28][29][30][31][32][33]37,[41][42][43]45,47,[49][50][51][52][53][54][55][56]58,64,69,70,74,77,78,[83][84][85][86][87][88][89][90] Across 27 studies, the use of this procedure varied from 15% to 82%, 16,18,[20][21][22][30]…”

Unfavorable Cancer-specific Survival After Neoadjuvant Chemotherapy and Radical Cystectomy in Patients With Bladder Cancer and Squamous Cell Variant: A Multi-institutional Study

“…Cisplatin-based neoadjuvant chemotherapy (NAC) is the standard of care in the management of patients with bladder cancer (BCa) who are candidates for radical cystectomy (RC) [1,2]. During the past few decades, several efforts have been spent to identify more active chemotherapy regimens and to enable appropriate patient selection through the use of clinical and genomic predictors of response to chemotherapy [3].…”

Urothelial cancer: a narrative review of the role of novel immunotherapeutic agents with particular reference to the management of non‐muscle‐invasive disease

“…Cystectomy is a major surgical and anaesthetic undertaking, with significant cost and quality‐of‐life implications and an overall 90‐day mortality of 4% (ranging from 2% in those aged < 70 years and 9% in those aged >80 years) . NMIBC is also difficult to stage accurately, with recent studies suggesting that high‐risk NMIBC invading the lamina propria is frequently understaged and is associated with a high risk of lymph node metastases and mortality . A substantial proportion of patients who have failed BCG with T1 tumours are upstaged at the time of surgery, with up to 10% found to have lymph node metastases .…”