NCCN Guidelines Insights: Bladder Cancer, Version 2.2016

Clark, Peter E.; Spiess, Philippe E.; Agarwal, Neeraj; Bangs, Rick; Boorjian, Stephen A.; Buyyounouski, Mark K.; Efstathiou, Jason A.; Flaig, Thomas W.; Friedlander, Terence W.; Greenberg, Richard E.; Guru, Khurshid A.; Hahn, Noah M.; Herr, Harry W.; Hoimes, Christopher J.; Inman, Brant A.; Kader, A. Karim; Kibel, Adam S.; Kuzel, Timothy M.; Lele, Subodh M.; Meeks, Joshua J.; Michalski, Jeff M.; Montgomery, Jeffrey S.; Pagliaro, Lance C.; Pal, Sumanta K.; Patterson, Anthony; Petrylak, Daniel P.; Plimack, Elizabeth R.; Pohar, Kamal S.; Porter, Michael P.; Sexton, Wade J.; Siefker-Radtke, Arlene; Sonpavde, Guru; Tward, Jonathan D.; Wile, Geoffrey; Dwyer, Mary A.; Smith, Courtney

doi:10.6004/jnccn.2016.0131

Cited by 94 publications

(84 citation statements)

References 74 publications

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“…According to current guidelines, neoadjuvant chemotherapy using cisplatin-based combination regimen is recommended in patients with cT2-4aN0M0 MIBC, and the use of adjuvant cisplatin-based combination chemotherapy is selectively recommended for patients with locally advanced (pT3/4) and/or lymph node-positive disease [45]. In the case of NMIBC, the use of intravesical treatment with bacillus Calmette-Guerin or chemotherapeutic agents after TURBT has been recommended, based on risk group stratification for recurrence and progression [51].…”

Section: Immune Checkpoint Inhibitors In Non-metastatic Mibc or Nmibcmentioning

confidence: 99%

“…For more than 30 years, cisplatin-based combination chemotherapy has been used as the standard of care in unresectable and metastatic/advanced UC, showing an overall response rate (ORR) of 40%–50% and a median overall survival (OS) of 14–15 months [45]. However, 40%–50% of patients with metastatic UC (mUC) do not qualify for cisplatin-based chemotherapy, owing to poor performance status and impaired renal function.…”

Section: Introductionmentioning

confidence: 99%

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Immune checkpoint inhibitors for urothelial carcinoma

Kim

Seo

2018

Investig Clin Urol

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Urothelial carcinoma (UC), originating in the bladder or upper urinary tract, is the most common histological type of cancer. Currently, platinum-based cytotoxic chemotherapy is the standard treatment for metastatic UC (mUC) and the preferred treatment option in the perioperative (neoadjuvant and/or adjuvant) setting of muscle invasive bladder cancer (MIBC). In addition, intravesical bacillus Calmette-Guerin immunotherapy or chemotherapy is applied as the adjuvant therapeutic option in non-muscle invasive bladder cancer (NMIBC) after transurethral resection, to prevent recurrence and progression. In recent years, with an increased understanding of cancer immunobiology, systemic immunotherapies targeting immune checkpoint inhibition has been explored and clinically used in the area of UC. The programmed cell death 1 receptor (PD-1) and its ligand (PD-L1) are important negative regulators of immune activity, preventing the destruction of normal tissues and autoimmunity. To date, five immune checkpoint inhibitors blocking PD-1 (pembrolizumab, nivolumab) or PD-L1 (atezolizumab, durvalumab, and avelumab) have been approved by the United States Food and Drug Administration (US-FDA) for first- or second-line use in mUC, based on durable therapeutic response and manageable safety profiles observed in relevant clinical trials. In addition, the clinical use of several immune checkpoint inhibitors is currently being tested for MIBC and NMIBC. In this article, we review the current and ongoing clinical trials, regarding immune checkpoint inhibitors, being conducted in various clinical settings of UC, including mUC, MIBC, and NMIBC.

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Section: Immune Checkpoint Inhibitors In Non-metastatic Mibc or Nmibcmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Immune checkpoint inhibitors for urothelial carcinoma

Kim

Seo

2018

Investig Clin Urol

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“…These features are considered to represent cT3 disease in patients with biopsy-proven MIBC, but have not been formally introduced into current staging systems or guidelines [6,7,19]. For this analysis, we excluded patients with a palpable 3D mass on EUA and the presence of neuroendocrine features because it is our practice to treat these patients uniformly with NAC [20].…”

Section: Discussionmentioning

confidence: 99%

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

Metcalfe

Ferguson

et al. 2017

European Urology Focus

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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.

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“…Furthermore, the recently published National Comprehensive Cancer Network (NCCN) Bladder Cancer Guidelines recommend broadening the scope of molecular profiling for advanced UC 43 in an effort to identify more patients with specific mutations as candidates for various ongoing clinical trials. In addition, those with higher mutational burden or specific tumor subtypes may be selected for immune checkpoint blockade.…”

Section: Targeted Therapy: Lessons Learned and Future Strategiesmentioning

confidence: 99%

New discoveries in the molecular landscape of bladder cancer

Kamat

Choi

et al. 2016

F1000Res

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We are currently on the cusp of exponential growth in the understanding of the molecular landscape of bladder cancer. Emerging data regarding the mutational burden and targetable genomic and protein alterations in bladder cancer have allowed us to tap into treatments directed toward specific molecular characteristics of bladder cancer. In parallel, these developments will enable us to better select patients for existing treatments of bladder cancer in a step toward personalized therapy. The present article reviews select discoveries that have advanced our understanding of bladder cancer and gives a glimpse of the exciting opportunities on the not-so-distant horizon.

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NCCN Guidelines Insights: Bladder Cancer, Version 2.2016

Cited by 94 publications

References 74 publications

Immune checkpoint inhibitors for urothelial carcinoma

Immune checkpoint inhibitors for urothelial carcinoma

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

New discoveries in the molecular landscape of bladder cancer

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