Stesura Seveso Archivio Italiano di Urologia e Andrologia 2024; 96(1):12404 1 LETTER TO EDITOR KEY WORDS: Bladder cancer; Office fulguration; Office laser; Local bladder treatment; NMIBC. Submitted 20 February 2024; Accepted 23 February 2024 To the Editor, Bladder cancer is one of the most common cancers in humans, representing the 7th and 17th type of neoplasm in both genders (1). Its incidence and mortality are quite heterogeneous in different countries and are due to different risk fac- tors, quality and prevalence of healthcare and the possibility of early diagnosis and treatment of the tumor and its poten- tial recurrences (2-3). Bladder cancer can be divided into muscle-invasive (MIBC) and non-muscle invasive (NMIBC). Early detection of the primary tumors and the recurrences is of paramount importance to enable a better prognosis (3). While MIBC is known to be treated very aggressively, i.e. with surgery, radiotherapy, and chemotherapy (4-8), NMIBC has a better prognosis but still has a high recurrence rate despite measures such as the use of local drugs. Although most of these recurrences in low-grade tumors guarantee a good prognosis if treated promptly with TURB, they still pose a management problem for both the patient and the healthcare system. Indeed, the patient is often forced to undergo multiple anesthesia, surgical and psychophysical stress related to hospital- ization and the anxiety of the operation itself. Furthermore, performing a transurethral resection of the bladder (TURB) may lead to transport management issues and organization problems for the patient's family. From a healthcare perspective, hospitalization for TURB requires an economic cost of several thousand euros, considering the cost of the surgical staff, the materials used during the operation and the hospital stay (9, 10). Furthermore, this contributes to longer waiting lists, which also has a negative impact on other patients. This problem is highly relevant, given the organizational prob- lems of healthcare systems and surgical waiting lists in the post-COVID era (11). Last but not least, there is the "green" problem considering that further hospitalization requires more surgical and hospi- tal supplies, an increase in travel for patients and relatives, and thus an impact on the carbon footprint. The EAU guidelines also include office-based fulguration and laser vaporization among the possible treatment options for NMIBC (3). Specifically, it states that that patients with a history of small Ta LG/G1 lesions can undergo fulguration or laser vaporization on an outpatient basis for small papillary recurrences. Outpatient treatment can be performed either by fulguration or using laser, generally under local anesthesia with instil- lation of intravesical lidocaine prior to the procedure and may warrant histologic examination by pre-fulguration biopsy. If HG is found, the patient can then be scheduled for TURB in the following weeks. The literature now presents numerous reports on the efficacy and safety of performing office-based procedures for the treatment of NMIBC (12-19). Recently, Vitug et al. evaluated the outcomes of fulguration in 270 patients with recurrent TaLG NMIBC in an outpatient setting (20). The 10-year incidence of cancer-specific mortality (CSM) and progression were Office-based management of Non-Muscle Invasive Bladder Cancer (NMIBC): A position paper on current state of the art and future perspectives Rosario Leonardi 1, 2, Francesca Ambrosini 3, Angelo Cafarelli 4, 2, Alessandro Calarco 5, 2, Renzo Colombo 6, 2, Domenico Tuzzolo 2, Ferdinando De Marco 7, 2, Giovanni Ferrari 8, 2, Giuseppe Ludovico 9, 2, Stefano Pecoraro 10, 2, Ottavio De Cobelli 11, 2, Carlo Terrone 12, Guglielmo Mantica 12 1 Casa di Cura Musumeci GECAS, Gravina di Catania, Italy; 2 Urologi Ospedalità Gestione Privata (UrOP), Italy; 3 IRCCS Policlinico San Martino, Genova, Italy; 4 Urology Unit, Villa Igea, Ancona, Italy; 5 Villa Pia Hospital, Rome, Italy; 6 Department of Urology, Vita e Salute San Raffaele University, Milan, Italy; 7 I.N.I. Grottaferrata, Rome, Italy; 8 Hesperia Hospital, Modena, Italy; 9 Ospedale Miulli, Acquaviva delle Fonti, Bari, Italy; 10 NEUROMED, Avellino, Italy; 11 Department of Urology, IEO European Institute of Oncology, IRCCS, Milan, Italy; 12 Department of Surgical and Diagnostic Integrated Sciences (DISC), University of Genova, Genova, Italy. DOI: 10.4081/aiua.2024.12404 Archivio Italiano di Urologia e Andrologia 2024; 96(1):12404 R. Leonardi, F. Ambrosini, A. Cafarelli, et al. 2 0% and 3.1%, respectively. They estimated a savings of nearly 7,000 Canadian dollars per patient. The savings in eco- nomic terms have also been demonstrated by other authors in other contexts (15, 21-23). Pedersen et al. in a prospective randomized controlled trial proved that laser photocoagulation in an outpatient setting is non-inferior to standard TURB for the 4-month recurrence rate (24). Halstuch et al. introduced an additional step, namely the use of a single dose of mitomycin (MMC), after performing office-based procedures such as fulguration (25). They found that a single dose of MMC instilled after fulguration was associated with longer recurrence free survival (RFS) compared to patients who did not receive MMC after the proce- dure, with no high-grade complications. One of the potential limitations of office-based procedures is the pain experienced by the patient. However, Strock et al. evaluated the pain perceived by patients during the procedure and obtained satisfactory results in this respect. The VAS scores after diagnostic cystoscopy report no or only mild pain in the totality of their case series. Despite the current evidence, we are still far from knowing which patients are safe candidates for these procedures (num- ber of lesions, size of lesions, number of previous TURB with histologic pTa LG/G1, age, etc.) and to consider these pro- cedures the "standard of care" in selected patients. We believe that outpatient treatment of NMIBC should be implemented for reasons of economic and environmental sus- tainability as well as for reasons of benefit to the patient, as illustrated previously. A stronger stance in national and inter- national guidelines in favor of these procedures in selected patients could be of fundamental importance. However, for the committees to move further in this direction, the scientific community must bring results from further randomized trials, perhaps multicenter, which can make the scientific evidence stronger. Furthermore, the definition of the ideal candidate for these procedures is un unmet need. Since it is now clear that that the patients for whom the treatments are indicated are patients with relapses of a previous pTa LG/G1 in the absence of rare variants of bladder cancer, some inclusion criteria need to be defined more precisely such as age, number of recur- rences/papillary lesions, time since the last TURB, etc. In this sense, the application of new biomarkers could become useful to define the patients with the highest risk and therefore not subject them to office-based treatment. Furthermore, the definition of the patient eligible for these procedures is also fundamental. It has now been established that the patients for whom the treatments are indicated are patients with relapses of previous pTa LG/G1 in the absence of rare variants of bladder cancer, some inclusion criteria must be defined in more detail such as age, the number of relapses/papillary lesions, time since last TURB, etc. In this sense, the application of new biomarkers could become useful to define the patients most at risk and therefore not candidate to office-based treatment (26). In conclusion, we believe that the office-based management of NMIBC should be much more under the spotlight of the scientific community. It is essential to properly define either the ideal candidates and the optimal settings. REFERENCES 1. Siregar GP, Parwati I, Noegroho BS, et al. The association between serum hypoxia inducible factor-1α level and urothelial bladder cancer: A preliminary study. Arch Ital Urol Androl. 2023; 95:11292. 2. MacDonald A, Mehrnoush V, Ismail A, et al. History of infantile BCG immunization did not predict lamina propria invasion and/or high-grade in patients with non-muscle invasive bladder cancer. Arch Ital Urol Androl. 2023; 95:11380. 3. EAU Guidelines. Edn. presented at the EAU Annual Congress Milan 2023. ISBN 978-94-92671-19-6. 4. Mantica G, Smelzo S, Ambrosini F, et al. Port-site metastasis and atypical recurrences after robotic-assisted radical cystectomy (RARC): an updated comprehensive and systematic review of current evidences. J Robot Surg. 2020; 14:805-812. 5. Maffezzini M, Fontana V, Pacchetti A, et al. Age above 70 years and Charlson Comorbidity Index higher than 3 are associated with reduced survival probabilities after radical cystectomy for bladder cancer. Data from a contemporary series of 334 consecutive patients. Arch Ital Urol Androl. 2021; 93:15-20. 6. Malinaric R, Mantica G, Balzarini F, et al. Extraperitoneal cystectomy with ureterocutaneostomy derivation in fragile patients - should it be performed more often? Arch Ital Urol Androl. 2022; 94:144-149. 7. Slovacek H, Zhuo J, Taylor JM. Approaches to Non-Muscle-Invasive Bladder Cancer. Curr Oncol Rep. 2021; 23:105. 8. Alvarez-Maestro M, Chierigo F, Mantica G, et al. The effect of neoadjuvant chemotherapy among patients undergoing radical cystectomy for variant histology bladder cancer: A systematic review. Arab J Urol. 2021; 20:1-13. 9. Joyce DD, Sharma V, Williams SB. Cost-Effectiveness and Economic Impact of Bladder Cancer Management: An Updated Review of the Literature. Pharmacoeconomics. 2023; 41:751-769. 10. Richters A, Aben KKH, Kiemeney LALM. The global burden of urinary bladder cancer: an update. World J Urol. 2020; 38:1895-1904. 11. Leonardi R, Bellinzoni P, Broglia L, et al. Hospital care in Departments defined as COVID-free: A proposal for a safe hospitalization pro- tecting healthcare professionals and patients not affected by COVID-19. Arch Ital Urol Androl. 2020; 92:67. 12. Soloway MS. Active Surveillance or Office Fulguration for Low Grade Ta Bladder Tumors: A Win-Win for Patients and Urologists. J Urol. 2018; 199:1120-1122. 13. Xu Y, Guan W, Chen W, et al. Comparing the treatment outcomes of potassium-titanyl-phosphate laser vaporization and transurethral elec- troresection for primary nonmuscle-invasive bladder cancer: A prospective, randomized study. Lasers Surg Med. 2015; 47:306-11. 14. Planelles Gómez J, Olmos Sánchez L, Cardosa Benet JJ, et al. Holmium YAG Photocoagulation: Safe and Economical Alternative to Transurethral Resection in Small Nonmuscle-Invasive Bladder Tumors. J Endourol. 2017; 31:674-678. 15. Green DA, Rink M, Cha EK, et al. Cost-effective treatment of low-risk carcinoma not invading bladder muscle. BJU Int. 2013; 111:E78-84. 16. Leonardi R, Vecco F, Iacona G, et al. TULA DUAL: Trans Urethral Laser Ablation of recurrent bladder tumors in outpatient setting. Arch Ital Urol Androl. 2023; 95:11171. 17. Ströck V, Holmäng S. Is bladder tumour fulguration under local anaesthesia more painful than cystoscopy only? Scand J Urol. 2020; 54:277- 280. 18. Meeks JJ, Herr HW. Office-based management of nonmuscle invasive bladder cancer. Urol Clin North Am. 2013; 40:473-9. 19. O'Neil BB, Lowrance WT. Office-based Bladder Tumor Fulguration and Surveillance: Indications and Techniques. Urol Clin North Am. 2013; 40:175-82. 20. Vitug C, Lajkosz K, Chavarriaga J, et al. Long-term outcomes and cost savings of office fulguration of papillary Ta low-grade bladder can- cer. BJU Int. 2024; 133:289-296. 21. Al Hussein Al Awamlh B, Lee R, Chughtai B, Donat SM, et al. A cost-effectiveness analysis of management of low-risk non-muscle-invasive bladder cancer using office-based fulguration. Urology. 2015; 85:381-6. 22. Wong KA, Zisengwe G, Athanasiou T, et al. Outpatient laser ablation of non-muscle-invasive bladder cancer: is it safe, tolerable and cost- effective? BJU Int. 2013; 112:561-7. 23. Svatek RS, Hollenbeck BK, Holmäng S, et al. The economics of bladder cancer: costs and considerations of caring for this disease. Eur Urol. 2014; 66:253-62. 24. Pedersen GL, Erikson MS, Mogensen K, et al. Outpatient Photodynamic Diagnosis-guided Laser Destruction of Bladder Tumors Is as Good as Conventional Inpatient Photodynamic Diagnosis-guided Transurethral Tumor Resection in Patients with Recurrent Intermediate-risk Low- grade Ta Bladder Tumors. A Prospective Randomized Noninferiority Clinical Trial. Eur Urol. 2023; 83:125-130. 25. Halstuch D, Lotan P, Karchever I, et al. Single-Dose Post-Office Fulguration Mitomycin C Instillation Appears to Improve Recurrence-Free Survival in Patients With Low-Grade Noninvasive Bladder Cancer. Clin Genitourin Cancer. 2023; 21:e320-e325. 26. Malinaric R, Mantica G, Lo Monaco L, et al. The Role of Novel Bladder Cancer Diagnostic and Surveillance Biomarkers-What Should a Urologist Really Know? Int J Environ Res Public Health. 2022; 19:9648. Archivio Italiano di Urologia e Andrologia 2024; 96(1):12404 3 Office-based management of Non-Muscle Invasive Bladder Cancer (NMIBC) Conflict of interest: The authors declare no potential conflict of interest. Correspondence Rosario Leonardi, MD - leonardi.r@tiscali.it Casa di Cura Musumeci GECAS, Gravina di Catania (CT), Italy Francesca Ambrosini, MD - f.ambrosini1@gmail.com Guglielmo Mantica, MD - guglielmo.mantica@gmail.com Carlo Terrone, MD - carlo.terrone@hsanmartino.it Department of Surgical and Diagnostic Integrated Sciences (DISC), University of Genova, Largo Rosanna Benzi 10, 16132, Genova, Italy Angelo Caffarell, MD - info@angelocafarelli.it Urology Unit, Villa Igea, Ancona, Italy Alessandro Calarco, MD - info@alessandrocalarco.com Villa Pia Hospital, Via Folco Portinari 5, Rome, Italy Renzo Colombo, MD - colombo.renzo@hsr.it Department of Urology, Vita e Salute San Raffaele University, Milan, Italy Domenico Tuzzolo, MD - info@casadelsole.it Urologi Ospedalità Gestione Privata (UrOP), Italy Ferdinando De Marco, MD - info@clinicavillamargherita.it I.N.I. Grottaferrata, Rome Giovanni Ferrari, MD - visite@giovanniferrariurologo.it Hesperia Hospital, Modena Giuseppe Ludovico, MD - g.ludovico@miulli.it Ospedale Miulli, Acquaviva delle Fonti, Bari, Italy Stefano Pecoraro, MD - cup@diagnosticamedica.org NEUROMED, Avellino, Italy Ottavio De Cobelli, MD - Ottavio.DeCobelli@unimi.it Department of Urology, IEO European Institute of Oncology, IRCCS, Milan, Italy