Paper Alert

Since the landmark publication by Grossman et al. neoadjuvant chemotherapy (NAC) with a combination of Methotrexate, Vinblastine, Adriamycin (doxorubicin) and cisplatin (MVAC) demonstrated a 5% advantage in overall survival (OS) compared with radical cystectomy (RC) alone, NAC followed by RC has become standard of care for managing muscle invasive bladder urothelial cancer (MIBC) in patients “able” and willing to undergo RC and cisplatin containing NAC.

It should probably be considered shameless self-advertising for the author of Paper Alert to highlight a clinical trial and subsequent articles related to it that he was study chair and senior author on, but there is some justification for doing this (for the first time since I’ve written Paper Alert), and I have received the “green light” from one of the editors (SPL) of Bladder Cancer.

So what does the patient with high grade, non-muscle invasive bladder cancer who has disease that is unresponsive to (or has quickly recurred after) adequate intravesical therapy with Bacillus Calmette Guerin (BCG) do, particularly if he (she) does not want to lose his (her) bladder? Two agents that received priority, fast track priority review by the Food and Drug Administration (FDA) for such patients, Vicinuim [1] and Nadofaragene (rAd-If Na/Syn 3) [2], which have efficacy in this circumstance have experienced production problems and are not available [3, 4].

Patients with newly diagnosed high risk (see below), high grade (HG) non-muscle invasive bladder cancer (NMIBC) have a significant likelihood of disease recurrence, progression and eventual death from BC [1, 2].

Patients with metastatic (M1) Urothelial cancer (UC) have an extremely ominous prognosis, with a 5 year survival rate of <5% after receiving cisplatin- based combination chemotherapy [1–3]. Thus, it is highly welcome news that within a year, two publications of Phase II (or I– II) trials of novel agents, erdafitinib [4] and enfortumab vedotin (EV) [5], have reported their efficacy and toxicity in patients with previously treated metastatic or unresectable UC.

Non-muscle invasive (NMI) urothelial cancer (UC) of the bladder has been responsive to intravesical therapy with live microorganisms (e.g. BCG) for well over 40 years [1] through mechanisms that induce direct cytotoxicity and more importantly, stimulation of the innate and adaptive immune systems.

Bladder recurrences of urothelial cancer after nephroureterectomy and bladder cuff excision (NU) for upper tract (UC) occur in about 30% of patients who’ve not had prior bladder cancers, with most of these occurring in the first year after surgery [1–4]. A single intravesical instillation of chemotherapy immediately after a transurethral resection of bladder tumor (TURBT) can significantly reduce the likelihood of tumor recurrence using a variety of agents (summarized in ref # 5) [5], but does it help after NU for UT UC? And if so, what agent should be used and when should it be administered?

There are many reasons to restrict administration of allogeneic perioperative blood transfusions (PBTs) including avoiding transfusion reactions, transmission of infections, sensitization against future transfusions and organ transplantations, and of course, “waste” of a precious and scarce resource. However, the one that concerns bladder cancer surgeons the most is having worse oncologic outcomes, particularly reducing cause specific (CSS) and overall survival (OS) for patients undergoing radical cystectomy.

The diagnosis of any cancer is a very serious event. It is thus not surprising that the response to such a diagnosis in many patients is despair, fear and concern. As one might expect, as a reflection of this psychological stress, the rate of suicide among patients receiving a new diagnosis of any cancer (except non-melanoma skin cancer) is 2 to 3 times higher than in the age and gender matched general population, being minimally higher with advanced age, slightly higher (1.28 times – but with overlapping 95% confidence intervals) in men than women, and higher yet in patients with pre-existing serious (requiring psychiatric hospitalization) psychiatric conditions.

Between 15 and 20% of patients with newly diagnosed urothelial cancer (UC) of the bladder will have high grade (HG) non-muscle invasive (NMI) disease including carcinoma-in-situ (CIS) and stage Ta and T1 tumors [1]. After transurethral resection of the cancer (TURBT), patients may undergo re-TURBT, but if no muscle invasive (MI) cancer is found most will receive an induction course of 6 weekly intravesical instillations of Bacillus Calmette Guerin (BCG).