Editing Non-Muscle Invasive Bladder Cancer (section)

===== Adverse events[https://pubmed.ncbi.nlm.nih.gov/30526332/] =====
* Most commonly occur in the first year of therapy
* Serious toxicity occurs in ≈5% of patients
* Pathogenesis
**Hypothesized mechanisms leading to adverse events (2):[https://pubmed.ncbi.nlm.nih.gov/11886488/]
**#Bacterial mediated: local, and possibly blood-borne, dissemination of the attenuated BCG strain
**#*Respond readily to antituberculous therapy, despite solid evidence of AFB infection
**#Non-bacterial mediated: sterile hypersensitivity reaction
**#*May be more delayed in appearance
**#*Responds readily to corticosteroids
*'''<span style="color:#ff0000">Clinically classified as local vs. systemic</span>'''
** '''<span style="color:#ff0000">Local</span>'''
*** Occurs in approximately 2/3 of patients
*** Result of BCG-contaminated urine
*** Can occur anywhere along the genitourinary tract
*** '''<span style="color:#ff0000">Most common local adverse event: cystitis-like symptoms</span>''' (hematuria, urgency, dysuria and increased urinary frequency)
**** Can occur in up to 71% of patients
**** Should be expected in the period immediately following BCG administration
**** Urinalysis and urine cultures do not yield evidence of infection
***** Must be distinguished from bacterial cystitis, which should demonstrate evidence of infection at urinalysis and/or in urine cultures and requires treatment with antibiotics.
**** Symptoms usually last 1–2 days; however, the degree and duration of symptoms tend to increase with subsequent BCG instillations
*** Other local adverse events
**** Bladder contracture
**** Prostate: granulomatous prostatitis, prostate abscess
***** '''Granulomatous prostatitis'''
****** Common following intravesical BCG therapy
****** May be due to reflux from the prostatic urethra to the prostatic ducts
****** Majority of patients with GP are asymptomatic
****** Can result in abnormal digital rectal exam or abnormal PSA
****** '''Appearance on MRI can mimic prostate cancer'''
****** '''Management'''
******* '''Asymptomatic: no intervention; if patient on maintenance BCG, can be continued.'''
**** Scrotum: granulomatous epididymo-orchitis, testicular abscess
**** Upper urinary tract: pyelonephritis, renal abscess, renal granuloma, ureteral stricture
**** Penis: balanitis
** '''<span style="color:#ff0000">Systemic</span>'''
*** Occurs in approximately 1/3 of patients
*** Result of BCG dissemination to other sites via the bloodstream
*** '''<span style="color:#ff0000">Most common systemic adverse event: fever</span>'''
**** Indicates adequate immune activation and is associated with a more favorable anti-tumor response
**** Usually mild (<38.5ºC), lasting for less than 48 hours and accompanied by malaise and nausea.
**** Persistent (> 48h) and high fever (> 38.5ºC) should prompt a complete workup for infection
*** '''<span style="color:#ff0000">Most serious systemic adverse event: sepsis</span>'''
**** '''Occurs in 1:15,000 patients'''
**** '''Potentially fatal'''
*** Other systemic adverse events
**** Malaise
**** Musculoskeletal: spondylodiscitis, intramuscular abscess, infected hardware, skin rash, arthralgia
**** Vascular: mycotic pseudoaneurysm
**** Pulmonary: pneumonitis
**** Hepatic: granulomatous hepatitis
**** Lymphatic: granulomatous lymphadenitis
**** Peritoneal: peritonitis
**** Opthalmic: choroiditis
**** Salivary: parotitis
****Endocrine: hypercalcemia from systemic granulomatosis[https://pubmed.ncbi.nlm.nih.gov/11886488/]
* '''Management'''
** '''See [https://www.cua.org/system/files/Guideline-Files/7367_NMIBC%2520Guideline_Epub.pdf Table 6] from 2021 CUA NMIBC Guidelines'''
** '''Isoniazid, rifampin, and cycloserine are used for systemic BCG toxicity'''
** Maneuvers to improve tolerability include reducing BCG dose and/or decreasing dwell time
*** The effect of BCG dose on toxicity is unclear