Rationale and Outcomes for Neoadjuvant Immunotherapy in Urothelial Carcinoma of the Bladder

Rouanne, Mathieu; Bajorin, Dean F.; Hannan, Raquibul; Galsky, Matthew D.; Williams, Stephen B.; Necchi, Andrea; Sharma, Padmanee; Powles, Thomas

doi:10.1016/j.euo.2020.06.009

Cited by 66 publications

(41 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…While we await the results of this trial, it is expected that the addition of Pembrolizumab will significantly improve pathologic response and event-free survival compared with adjuvant chemoradiotherapy alone. In addition, Pembrolizumab has been shown to be an effective neoadjuvant agent that significantly improves patient survival in other cancers, including malignant melanoma, bladder cancer and lung cancer (31)(32)(33). Phase III trials in various solid cancers are currently underway to confirm the results of the present preliminary studies in a large patient population (NCT03036488, NCT03221426).…”

Section: Discussionmentioning

confidence: 69%

Neoadjuvant Immunotherapy of Oral Squamous Cell Carcinoma: Case Report and Assessment of Histological Response

et al. 2021

View full text Add to dashboard Cite

BackgroundThe treatment of oral cancer remains challenging due to its infiltrative nature and a high tendency for tumour relapse leading to an overall poor prognosis. In the case of early recurrence, the patient’s prognosis deteriorates dramatically, with survival rate dropping to below 30%. Minimal improvements in survival trends in recurrent and advanced stage tumours have been reported in recent decades. Neoadjuvant immunotherapy may represent a new therapeutic approach changing the standard of care in advanced oral cancer therapy.Case PresentationWe describe the case of a woman in her late 30’s who presented in mid-2019 with oral squamous cell carcinoma (OSCC) localized to the floor of the mouth. After initial R0 resection, selective neck dissection, and adjuvant brachytherapy, an early recurrence of OSCC located between the hyoid bone and the mandible was diagnosed at the end of 2019. An off-label treatment regimen was performed with neoadjuvant use of Pembrolizumab 19 days prior to salvage surgery. Radiological and histological assessment of T-cell and programmed cell death protein 1 ligand 1 (PD-L1) expression was performed before and after checkpoint inhibitor application. Neoadjuvant immunotherapy resulted in increased T-cell infiltration and PD-L1 expression, as well as a significant tumour necrosis rate. One cycle of Pembrolizumab led to significant regressive tumour changes with increases in immune infiltration, sclerosis, and necrosis of 75% of the tumour mass with only 25% vital tumour cells remaining. By June 2020, the patient remained without recurrence.ConclusionsThe case presented outlines the potential effects of neoadjuvant immunotherapy in recurrent or advanced OSCC prior to definitive surgical tumour treatment. The benefit of additional adjuvant treatment after histologic response will be discussed. The case is also analysed considering ongoing clinical trials of neoadjuvant immunotherapy for head and neck malignancies.

show abstract

Section: Discussionmentioning

confidence: 69%

Neoadjuvant Immunotherapy of Oral Squamous Cell Carcinoma: Case Report and Assessment of Histological Response

et al. 2021

View full text Add to dashboard Cite

show abstract

“…This may become more relevant in the near future, with the expected use of novel therapies, such as immunotherapy, in the perioperative setting of non-metastatic MIBC. 26 …”

Section: Discussionmentioning

confidence: 99%

Referral for “Neoadjuvant Chemotherapy” for Muscle-Invasive Bladder Cancer to a Multidisciplinary Board: Patterns, Management and Outcomes

Dellis

Zakopoulou

Kougioumtzopoulou

et al. 2021

CMAR

View full text Add to dashboard Cite

Background Utilization of neoadjuvant chemotherapy for the treatment of muscle invasive bladder cancer in everyday practice differs from that of clinical trials. We describe the patterns of referral for “neoadjuvant chemotherapy”, treatment and outcomes in a multidisciplinary tumor board. Methods This was an observational study. Patients referred for neoadjuvant chemotherapy received 4 cycles of dose-dense gemcitabine/cisplatin and were then assessed for definitive local therapy. Patients had a minimum follow-up of 2 years. Primary objective was a 3-year disease-free survival rate. Results Forty-six patients (clinical stages II: 28, IIIA: 9, IIIB: 4, IVA: 3, missing: 2) were included. Following chemotherapy, 30 underwent radical cystectomy, 8 radiotherapy and 8 no further therapy. Pathological downstaging was observed in 14 (46.6%) of the 30 patients who underwent radical cystectomy; clinical TNM staging was correlated with disease-free survival in the whole population, while clinical and pathological stages, as well as pathological downstaging, were correlated with disease-free survival in patients undergoing radical cystectomy. Three-year disease-free survival rates for the whole cohort and for patients undergoing radical cystectomy were 67.3% (95% confidence interval [CI]: 51–79.2) and 65.2 (95% CI: 44.9–79.6), respectively. Conclusion Real-world muscle invasive bladder cancer patients who receive neoadjuvant chemotherapy are characterized by more advanced diseases and less frequent radical surgery than those included in clinical trials. Nevertheless, outcomes were comparable and, therefore, offering patients with stage II–IVA muscle invasive bladder cancer neoadjuvant chemotherapy after assessment by multidisciplinary tumor boards should be strongly encouraged.

show abstract

“…The ABACUS phase II study reported a pCR rate of 31% and the majority of patients underwent surgery successfully after neoadjuvant atezolizumab therapy ( 50 ). Encouraged by these results, a series of phase III trials assessing ICIs as monotherapy or in combination have been initiated ( 51 ). Although neoadjuvant ICIs demonstrate promising antitumor activity, they also pose new challenges in clinical decision-making ( 52 ).…”

Section: The Advances and Challenges Of Immunotherapy For Ubcmentioning

confidence: 99%

Immunotherapy in the Treatment of Urothelial Bladder Cancer: Insights From Single-Cell Analysis

Zang

Yang

et al. 2021

Front. Oncol.

View full text Add to dashboard Cite

Urothelial bladder cancer (UBC) is a global challenge of public health with limited therapeutic options. Although the emergence of cancer immunotherapy, most notably immune checkpoint inhibitors, represents a major breakthrough in the past decade, many patients still suffer from unsatisfactory clinical outcome. A thorough understanding of the fundamental cellular and molecular mechanisms responsible for antitumor immunity may lead to optimized treatment guidelines and new immunotherapeutic strategies. With technological developments and protocol refinements, single-cell approaches have become powerful tools that provide unprecedented insights into the kaleidoscopic tumor microenvironment and intricate cell-cell communications. In this review, we summarize recent applications of single-cell analysis in characterizing the UBC multicellular ecosystem, and discuss how to leverage the high-resolution information for more effective immune-based therapies.

show abstract

Rationale and Outcomes for Neoadjuvant Immunotherapy in Urothelial Carcinoma of the Bladder

Cited by 66 publications

References 40 publications

Neoadjuvant Immunotherapy of Oral Squamous Cell Carcinoma: Case Report and Assessment of Histological Response

Neoadjuvant Immunotherapy of Oral Squamous Cell Carcinoma: Case Report and Assessment of Histological Response

Referral for “Neoadjuvant Chemotherapy” for Muscle-Invasive Bladder Cancer to a Multidisciplinary Board: Patterns, Management and Outcomes

Immunotherapy in the Treatment of Urothelial Bladder Cancer: Insights From Single-Cell Analysis

Contact Info

Product

Resources

About