A 2019 Canadian Urological Association best practice report on the management of hemorrhagic cystitis in the pediatric population states that clinicians can consider sclerotherapy with formalin in severe, refractory cases, but as a last resort prior to irreversible surgical options (Level 3 evidence, Grade D recommendation). Given that instillation is painful, general anesthesia is required and it is recommended that all patients undergo evaluation for vesicoureteral reflux (VUR) beforehand to prevent upper-tract injury. If VUR is present, ureteral orifices may be temporarily occluded during treatment with Fogarty catheters. Reports using 4% formalin have been effective with some children improving after a single treatment while lower concentrations (1-2%) have been effective but required multiple instillations. The guideline emphasizes that due to potential long-term bladder compromise (e.g., bladder scarring), formalin should be typically avoided or use as a last resort, especially in the pediatric population. [1]
Recent reviews consistently describe formalin as a last‑line intervention for severe, refractory hemorrhagic cystitis due to its significant toxicity profile and lack of guideline endorsement. Its hemostatic efficacy and clinical outcomes vary widely, with reported response rates ranging from 75-89%, however, often followed by recurrence or progression to bladder dysfunction. Lower concentrations (1-2%) may achieve control but frequently require repeat instillations, whereas higher concentrations (≥4%) correlate with greater systemic absorption, ureteral injury, severe fibrosis, and increased risk of major complications, including ureteral strictures, bladder contracture, vesicovaginal fistula, vesicorectal fistula, and even formalin‑related deaths. Several studies report that up to 31-40% of patients ultimately require urinary diversion or cystectomy because of formalin‑related damage. Formalin exposure also raises theoretical carcinogenic concerns due to formaldehyde classification, though long‑term cancer risk data remain insufficient. Overall, while formalin can rapidly control life‑threatening hematuria, its dose‑dependent toxicity and risk of irreversible injury limit its use to carefully selected cases when all safer options have failed. [2], [3], [4]
Additional reviews highlight that given radiotherapy commonly involves cancers in the lower abdomen and pelvis, the bladder and urinary tract are frequently exposed to radiation increasing the risk of developing radiation-induced hemorrhagic cystitis. Bladder instillation with formalin is again discussed as a treatment option for clinically significant gross hematuria or hemorrhagic cystitis only when other supportive measures and treatments have failed and surgery is being considered. One review notes that while formalin concentrations of 1-10% have been used, maximum dilution is preferred due to increased toxicity with higher concentration and that the instillation should not exceed 15 minutes. Treatment success with formalin has ranged from 70-90%; however, its use is associated with major complications such as ureter obstruction, renal failure, and formalin reflux into the upper urinary tract leading to bilateral pyonephrosis with lethal sepsis. [5], [6]
A 1990 retrospective review evaluated the treatment and clinical outcomes of a cohort of 25 patients (mean age 65 years) with massive hemorrhagic cystitis who received intravesical instillation of formalin from 1980 to 1988. The hemorrhagic episodes primarily stemmed from pelvic radiotherapy in 15 cases, cyclophosphamide therapy in one case, and infiltrating bladder cancer in the remaining nine cases. Of these patients, 19 were treated with a 4% formalin solution, while the remaining six received a 10% solution. The instillation was performed, under general or intradural anesthesia, with a maximum contact time of 15 minutes in 80% of patients. Notably, 10 patients underwent the procedure with prior supravesical urinary diversion, such as ileal conduits or percutaneous nephrostomies, which accounted for approximately 40% of the treatments conducted in 'excluded' bladders (without passage of urine). Immediately after the instillation with formalin, bladder lavage was performed using 10% alcohol and a continuous bladder irrigation with normal saline for 24-48 hours. The review documented good outcomes in 88% of cases, with effective hemostasis achieved for an average duration of four months. Complications were more frequent with the use of the 10% formalin concentration. Specifically, one case each of vesicorectal fistula, uretero-hydronephrosis, and vesical extravasation of formalin were noted when higher concentration and volume were used. In contrast, the use of 4% formalin was associated with a complication of upper urinary tract dilatation in only one instance. These findings underscore that lower concentrations and smaller volumes of formalin result in fewer complications, advocating the use of 4% formalin for managing massive hemorrhagic cystitis when conservative measures fail to control bleeding. [7]