Real-World Safety of Prostate Cancer Focal Therapy: MAUDE Database Analysis

Introduction

Prostate cancer is the most commonly diagnosed solid organ cancer among men in the United States, affecting 268,000 men a year. ¹ Focal therapy or focal ablation is a newer management option for prostate cancer, challenging conventional treatment methods like surgery and radiation therapy. ^2,3 This minimally invasive approach leverages image guidance to target only cancerous tissue within the prostate, thereby minimizing damage to surrounding healthy tissue. ⁴ Due to its precision, focal therapy reduces the incidence of debilitating side effects commonly associated with traditional prostate cancer treatments, such as sexual dysfunction and urinary incontinence. ⁵

A variety of energy sources delivered via numerous commercially available focal therapy platforms have been applied in the treatment of prostate cancers. ⁴ Currently, the focal therapy devices approved by the United States Food and Drug Administration (FDA) to ablate the prostate tissue use a variety of energy sources, including high-intensity focused ultrasound (HIFU), cryoablation, laser ablation, and irreversible electroporation (IRE). ⁴

Despite the growing clinical application of these techniques, there remains a notable gap in the literature regarding their safety profiles, as most data came from short- or intermediate-term single-institutional series. ^6,7 The Manufacturer and User Facility Device Experience (MAUDE) database, maintained by the FDA, is a valuable publicly available data source for monitoring the safety of medical devices, including those used in focal therapy. ⁸ The database provides real-world data on adverse events and complications associated with medical devices, offering a unique lens through which the safety of focal therapy devices can be scrutinized. Previous studies leveraging the MAUDE database have provided valuable insights into the safety of various surgical devices. ^{9 –11} However, there is an absence of studies focusing on focal therapy devices for prostate cancer. Our study aims to address this knowledge gap by conducting a comprehensive review of the MAUDE database, focusing specifically on the focal therapy devices for prostate cancer. By identifying and analyzing reports related to these focal therapy techniques, our study seeks to elucidate the safety profile of these emerging treatments.

Materials and Methods

Results

Discussion

Focal therapy is an exciting option in prostate cancer management, offering a minimally invasive alternative to conventional treatments. By leveraging real-world data from the MAUDE database, our study fills a critical gap in understanding the safety profiles of prostate cancer focal therapies such as HIFU, cryoablation, laser ablation, and IRE. To our knowledge, this is the first study on the subject using the MAUDE database. Our analysis revealed a predominantly favorable safety profile. However, significant complications like rectal fistulas and death after focal therapy highlight the need for meticulous patient selection and procedural planning.

The majority of the adverse events captured in our study were minor, classified as Clavien-Dindo grade I or II. These findings, although not directly translatable to complication rates due to the nature of the MAUDE database, suggest that the incidences of minor complications are within an expected range for minimally invasive procedures. ^{2,7,12 –15} Given the predominance of minor complications observed in our study, it underscores the necessity for physicians to accurately inform patients about possible postoperative outcomes following focal therapy. This education should cover manageable but common issues like urinary retention, erectile dysfunction, infections, lower urinary tract symptoms, and transient hematuria. Additionally, it emphasizes the need for vigilant postoperative follow-up to promptly address these complications, ensuring optimal patient care and recovery. This observation aligns with the existing narrative within the field that focal therapy presents a viable, less invasive option for prostate cancer management with a manageable side effect profile. ^16,17

Despite the reassuring profile of predominantly minor complications, our analysis also sheds light on more severe adverse events, notably rectal injuries and a rare instance of mortality. Rectal injuries, particularly fistulas, represent a significant concern due to their potential for requiring complex surgical intervention and the subsequent impact on patient quality of life. The occurrence of such complications, although infrequent, emphasizes the critical importance of careful procedural planning and judicious patient selection, especially considering the salvage therapy context where the risk appears elevated. ^13,14,17,18 Although the MAUDE database identified a limited number of these complications, it is important to recognize that this passive surveillance system likely underreports the true incidence. ¹⁹ Considering the large number of focal therapy procedures performed and the relatively few rectal fistula cases reported in MAUDE, the actual rate of this complication is likely low. The noted case of mortality, though rare, serves as a stark reminder of the inherent risks associated with any procedural intervention, including those related to anesthesia and procedural immobilization. These rare complications should be emphasized as much as the favorable side effect profiles of focal therapy compared with traditional local treatments like surgery and radiation. These findings highlight the imperative for comprehensive preoperative counseling that communicates the risks of severe complications against the backdrop of prostate cancer’s typically slow progression. ²⁰ The decision-making process should incorporate a thorough consideration of the patient’s overall health status, the pathology of cancer, and the potential benefits and risks of undergoing focal therapy.

As focal therapy technologies advance, HIFU has become increasingly popular for its precision, minimally invasiveness, and smooth learning curve. Various HIFU devices, delivering energy either transrectally (Focal One, Ablatherm, Sonablate, and Exablate) or transurethrally (TULSA), could potentially exhibit differing side effect profiles based on their approach. The current dataset, leaning toward older technologies, hints at a transitional phase in focal therapy, where the full spectrum of adverse events associated with newer modalities continues to manifest. The evolving landscape underscores the critical need for ongoing research and surveillance. Our study captured a singular case of TULSA complicated by rectal perforation. This surprising incident, occurring during an attempt to insert a cooling probe into the rectum of a previously radiated patient, underscores the nuanced importance of vigilance and continuous monitoring in a focal therapy modality that theoretically carries lower risks for rectal injury. This is also very relevant for newer technologies like IRE, which have only two MAUDE reports, both of which are two severe rectal injuries. These humbling incidents highlight the need for transparency in reporting about the safety of new treatment options.

Our study is not without its limitations. The MAUDE database is inherently subject to self-reporting bias, with reports varying significantly in the level of detail provided. A significant limitation is the lack of granularity in the reported data, particularly regarding patient demographics, the precise nature of the disease, and treatment (e.g., presence of locally advanced disease; whether whole gland or partial gland ablation was performed). Furthermore, the MAUDE database does not provide longitudinal follow-up information, leaving us without insights into disease recurrence, patient survival, or the long-term functional outcomes from these complications. This gap precludes a comprehensive understanding of the adverse events’ impact over time and prevents an assessment of how patient history or pre-existing conditions such as prior radiation therapy may influence susceptibility to specific complications. Additionally, there is no data on the device usage rate, so these safety event reports cannot be used to extrapolate patient-level adverse event risks as the total cases performed are unknown.

Despite these challenges, the study draws its strength from the MAUDE database’s extensive scope and longitudinal maintenance as an FDA medical device surveillance tool. Its large sample size and broad coverage of national data offer an unparalleled overview of real-world adverse event reporting for various focal therapy devices. This analysis stands as the first to comprehensively review the safety profiles of multiple focal therapy modalities for prostate cancer treatment, marking a significant contribution to the field’s understanding of these emerging treatment options.

Conclusion

Our study is the first to utilize the MAUDE database to examine the safety of focal therapies such as HIFU, cryoablation, laser ablation, and IRE for prostate cancer. We found that these novel treatment options exhibited generally minor complications. However, the presence of serious complications, like rectal injuries and death, highlights the need for careful selection of patients and detailed planning of procedures. With the continued innovations in focal therapy technology, the need for vigilant ongoing research and transparent reporting becomes paramount.