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

Abstract

AimThis narrative review describes current guidelines for treating NMIBC, provides an overview of the principle behind immune checkpoint inhibition, and summarizes current evidence for checkpoint inhibitors in urothelial malignancy. Further, we discuss potential strategies for immune checkpoint inhibition in the management of NMIBC. ConclusionThere has been little advance in available adjuvant therapy for NMIBC treated with TURBT. Current intravesical therapies are associated with a high recurrence rate and significant side effect profile. The impending publication of the wealth of ongoing trials, both into the delivery and efficacy of checkpoint inhibition will direct the future treatment of NMIBC. ReviewPotential factors related to BCG failure include insufficient or excess BCG, presence of subclinical micro-metastatic disease at time of diagnosis, and inadequate immune 948

Update on the guideline of guidelines: non‐muscle‐invasive bladder cancer

“…Vicinium, another fusion protein aimed at tumour regression, has shown early CRRs of 14% in unresponsive patients with carcinoma in situ at 12 months of treatment in a phase III trial . We can expect further clarity on not only the disease efficacy, but also the toxicity patterns, cost and ideal delivery methods as these trials are published in the coming years . It should also be noted that many of these trials are actively recruiting and should be considered as options in settings of BCG failure or decreased BCG supply.…”

The natural history of untreated muscle‐invasive bladder cancer

“…However, this treatment modality is associated with grade 3–4 toxicity in slightly >35% of the recipients and some elderly patients may not be ideal candidates for NAC administration. Studies aimed at evaluating the role of novel potential treatments, including immunotherapy, both in the neo‐ and adjuvant setting are ongoing, suggesting promising results with potentially better tolerability profiles are ongoing , and these treatment modalities could potentially be more suitable in cases of advanced age at presentation. One of the limitations of our present study was the minimal use of chemotherapy given the time of diagnosis, 1995–1996, when chemotherapy was not yet the standard of care.…”

Nonmuscle invasive urothelial cancer— Bacillus Calmette–Guérin instillation or checkpoint inhibitor immunotherapy?

“…Side effects are usually self-limiting, and only some patients need short-course immunosuppressive drugs or TNFα-receptor antagonists when glucocorticoids fail [21]. Response to CKIs depends on multiple factors involving molecular characteristics of the tumor and interaction with the immune system, but expression of PD-1/PD-L1, tumor mutational burden and tumor immune infiltration seem to play a role for adequate response [22]. In bladder cancer, NMIBC tumors have been reported to express lower levels of PD-1 than MIBC, but BCG infection can induce PD-L1 expression in regulatory T-cells [23].…”