Elevating Patient Care: A Urologist's Vision for New Standards After First-Line No Longer Works

By Ravi D. Chauhan, M.D., F.A.C.S
Board-certified urologist
Conrad Pearson Clinic in Germantown, TN
Specializing in minimally invasive and advanced surgical techniques for urologic conditions

A treatment’s safety and efficacy remain the gold standard in therapeutic innovation, but the most transformative medicines also succeed on another critical front: how seamlessly they integrate into a patient’s life. This measure of success has become increasingly relevant as we better understand how treatment burden, frequency, and level of life disruption can influence both adherence and outcomes.

This challenge is particularly evident in non-muscle invasive bladder cancer (NMIBC), where a diagnosis can demand frequent clinic visits and can significantly impact a patient’s life. As a urologist, I've learned that effectively managing NMIBC requires an understanding of my patient’s perspectives, easing their concerns, preserving their quality of life, and minimizing the daily disruptions caused by therapy.

Bacillus Calmette-Guérin (BCG) has long been the standard of care for NMIBC, but it has critical limitations.¹ About one in three patients fail to respond to BCG.¹ Among those who initially benefit, nearly half will ultimately experience disease recurrence or progression.² When BCG fails, patients often face difficult and life-altering decisions, including the prospect of undergoing bladder removal surgery (cystectomy), which can lead to serious side effects and life-altering changes to the body.

Beyond clinical challenges, NMIBC takes an emotional toll. Some low-risk patients overestimate the risk of their disease, in contrast to some high-risk patients, who may not grasp the severity of their condition. This may lead to delays in treatment or poor adherence to prescribed treatment. These circumstances underscore the need for patient-centered therapies that not only drive outcomes but also fit into a patient’s quality of life and support long-term management. 

ADSTILADRIN^® (nadofaragene firadenovec-vncg): A Valuable Option for Patients

The U.S. Food and Drug Administration (FDA) approved ADSTILADRIN^® (nadofaragene firadenovec) in December 2022. This represented a breakthrough for patients with BCG-unresponsive NMIBC with carcinoma in situ (CIS) with or without papillary tumors (±Ta/T1).³ As the first and only intravesical non-replicating gene therapy for this patient population, ADSTILADRIN delivers a copy of the gene encoding human interferon alpha 2B (IFNα2b)—which has antitumor activity—to the bladder cells allowing the body’s natural immune system to fight cancer. It offers a tolerable and effective bladder-sparing treatment option through a familiar route of administration.

When discussing therapies with my patients, they often ask two questions: "Will it work?” and “What are the side effects?" In clinical trials, ADSTILADRIN demonstrated efficacy and a tolerable safety profile. The pivotal Phase 3, multicenter, single-arm, open-label trial that led to its approval found that 51% (50/98) of patients with CIS +/- high-grade Ta/T1 had a complete response (CR) by three months (with no signs of high-grade bladder cancer) after a single instillation of ADSTILADRIN. Of those patients (n=50) who achieved a complete response, 46% remained free of high-grade recurrence at 12 months.

The study also established the safety profile of ADSTILADRIN. The most common adverse reactions observed in the study were instillation site discharge (leakage of medicine from the bladder) (33%), fatigue (24%), bladder spasm (20%), urinary urgency (19%), and blood in the urine (17%). These adverse reactions were mild to moderate in intensity, generally resolving in about two days. Less than 2% of patients discontinued treatment due to adverse reactions. ADSTILADRIN has a consistent body of evidence for patients with NMIBC.⁴

A Treatment Designed with the Patient in Mind

Beyond efficacy and safety, the ability for a treatment to seamlessly integrate into a patient’s life matters greatly. My patients tell me that the quarterly dosing regimen of ADSTILADRIN fits well within their lifestyle and schedule.

ADSTILADRIN is delivered at the urologist’s office directly into the bladder for one hour, only once every three months. This is a stark contrast to the more frequent visits required for BCG or other in-bladder treatments, requiring bladder instillation once a week for six weeks. ADSTILADRIN allows patients more time to continue their daily activities. In addition to a quarterly maintenance schedule, ADSTILADRIN offers patients a familiar treatment delivery option that doesn't require additional needles or devices.

From a practice standpoint, ADSTILADRIN is straightforward to deliver. The instillation process mirrors that of BCG, a method of administration with which the nursing staff are already well versed. Treatment also does not require mixing, dilution, or co-administration with other therapies. This means my staff has more time to focus on what matters most—supporting patients through every step of their NMIBC journey. For my patients, ADSTILADRIN means fewer clinic visits, less disruption to their lives, and renewed optimism for bladder preservation.

Growing Clinical Evidence in the Real World

Ongoing research continues to establish the safety and efficacy of ADSTILADRIN. There is real-world evidence helping us understand how treatments truly serve patients in day-to-day practice. Recently, Mayo Clinic conducted an independent retrospective assessment (n=46) of patients commercially treated with ADSTILADRIN, providing the first real-world evidence of its efficacy and tolerability, and supporting its use in practice.⁵ Among 24 evaluable patients with BCG-unresponsive CIS +/- high-grade Ta/T1, 79% (19/24) achieved a complete response at three months—and, encouragingly, 84% (16/19) maintained their response at a median follow-up of 7.3 months, with the median duration of response not yet reached, indicating sustained efficacy. The most common adverse reactions were grade 1-2 bladder spasms (61%) and failure to retain drug for the full hour (33%). Four patients experienced grade 3 reactions; no grade 4-5 reactions occurred, and no patients discontinued treatment due to adverse reactions. These data from a multi-site single institution were not funded or supported by Ferring Pharmaceuticals.

Further reinforcing the findings, Ferring also announced interim results from an ongoing Phase 3b trial of ADSTILADRIN in BCG-unresponsive CIS ± high-grade Ta/T1 patients (n=20) in Japan. At three months, 75% (15/20) of patients achieved a complete response.⁶ Overall, 80% of participants experienced a drug-related adverse reaction, all of which were either Grade 1 (84.2%) or Grade 2 (15.8%). Observing this research, I am hopeful these studies will continue building on the growing body of evidence that supports the emerging role of ADSTILADRIN as a new standard of care and a potential backbone therapy for NMIBC patients.

The Promise of a Bladder-Sparing Future

Bladder cancer is considered a “high touch” disease as we see our patients frequently, and those ongoing encounters often shape the patient experience as much as the disease itself. Some of the most rewarding moments in my practice are when I scope a patient and see no evidence of recurrent NMIBC.

While NMIBC is a complex and aggressive disease that can challenge even our most advanced therapies, ADSTILADRIN offers something critical: the ability to treat patients effectively while potentially minimizing the disruption to their daily lives. It lightens the burden of constant appointments, offers additional hope after BCG failure, and provides an opportunity to avoid cystectomy.

For physicians like me, ADSTILADRIN represents a meaningful shift in how we manage NMIBC—one that puts efficacy, tolerability, and the patient’s everyday life at the center of care.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS: ADSTILADRIN is contraindicated in patients with prior hypersensitivity reactions to interferon alfa or to any component of the product.

WARNINGS AND PRECAUTIONS:

• Risk with delayed cystectomy: Delaying cystectomy in patients with BCG-unresponsive CIS could lead to development of muscle invasive or metastatic bladder cancer, which can be lethal. If patients with CIS do not have a complete response to treatment after 3 months or if CIS recurs, consider cystectomy.
• Risk of disseminated adenovirus infection: Persons who are immunocompromised or immunodeficient may be at risk for disseminated infection from ADSTILADRIN due to low levels of replication-competent adenovirus. Avoid ADSTILADRIN exposure to immunocompromised or immunodeficient individuals.

DOSAGE AND ADMINISTRATION: Administer ADSTILADRIN by intravesical instillation only. ADSTILADRIN is not for intravenous use, topical use, or oral administration.

USE IN SPECIFIC POPULATIONS: Advise females of reproductive potential to use effective contraception during ADSTILADRIN treatment and for 6 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during ADSTILADRIN treatment and for 3 months after the last dose.

ADVERSE REACTIONS: The most common (>10%) adverse reactions, including laboratory abnormalities (>15%), were glucose increased, instillation site discharge, triglycerides increased, fatigue, bladder spasm, micturition (urination urgency), creatinine increased, hematuria (blood in urine), phosphate decreased, chills, pyrexia (fever), and dysuria (painful urination).

You are encouraged to report negative side effects of prescription drugs to FDA. Visit www.FDA.gov/medwatch or call 1-800-332-1088. You may also contact Ferring Pharmaceuticals at 1-888-FERRING.

Please click to see the full Prescribing Information.