Endoscopic Management of Upper Tract Urothelial Carcinoma: New Lasers and Techniques
By: Raymond Khargi, MD, Icahn School of Medicine at Mount Sinai, New York, New York; Alan J. Yaghoubian, MD, Icahn School of Medicine at Mount Sinai, New York, New York; Anna Ricapito, MD, Icahn School of Medicine at Mount Sinai, New York, New York, University of Foggia, Italy; Mantu Gupta, MD, Icahn School of Medicine at Mount Sinai, New York, New York | Posted on: 09 Mar 2023
Upper tract urothelial carcinoma (UTUC) is a heterogeneous group of malignancies that accounts for 5%-10% of all urothelial carcinomas. Approximately 30% of UTUCs are diagnosed as low grade upon clinical presentation.1,2 In past years, due to the anatomical intricacy of the upper tracts and the potential of recurrence and progression, low-grade UTUCs were frequently treated in the same manner as high-grade UTUCs, for which radical nephroureterectomy and bladder cuff excision is the current gold standard. However, recent advances in ureteroscopic and laser technologies have made endoscopic kidney-sparing surgery a viable treatment option for low-risk UTUC. According to the European Association of Urology guidelines, favorable clinical and pathological criteria for endoscopic management of UTUC are as follows: low-grade histology based on cytology and biopsy; papillary architecture; tumor size less than 2 cm; unifocality; and cross-sectional imaging demonstrating no invasive disease.1 In addition, it may be carefully considered for a subset of high-risk patients with severe renal insufficiency or a solitary kidney.
Current endoscopic therapy options for UTUC consist of a retrograde procedure involving ureteroscopy, tumor biopsy, and ablation, and an antegrade percutaneous method involving excision and fulguration. Antegrade techniques have been reserved for large, bulky tumors and otherwise difficult-to-reach parts of the collecting system in which ureteroscopy has failed. As such, retrograde ablation is the most popular method employed by the urological community and can be dated back to the era of small electrocautery probes placed through ureteroscopes. Electrocautery had the drawbacks of being unable to ablate larger tumors due to the inability to remove treated tissue, causing charring requiring frequent cleaning of the probe and lack of precise control with resultant thermal effects on surrounding healthy tissue. Lasers provided a tremendous advance in terms of precision, but early lasers such as the neodymium:yttrium-aluminum-garnet (Nd:YAG), with its 1,064 nm continuous wavelength, while providing excellent hemostasis and ablation, lacked the ability to remove ablated tissue, preventing visualization of deeper layers of tumor and preventing the treatment of larger tumors. Newer laser technologies are available, but unfortunately, surgeons have been left to their own devices when deciding which laser technology is best for UTUC management, as there is currently no clear guidance on the subject.
Holmium:YAG (Ho:YAG) lasers became the default laser for the endoscopic treatment of upper tract tumors for the last 3 decades due to their widespread availability and dependability in the field of stone management, as opposed to their specific efficacy in tumor ablation. The ability to deliver energy through smaller fiber sizes compared to electrocautery electrodes allows better irrigation flow and visualization, whether using flexible or semirigid ureteroscopes. It is a solid-state laser with a wavelength of 2,100 nm and a 0.5 mm penetration depth. It operates in a pulsatile mode and is better absorbed by water, which is the main constituent of body tissues.3 Unlike the Nd:YAG laser, it can “vaporize” tissue via a photothermal effect, not just ablate it, allowing treatment of deeper layers of tumor and, therefore, larger tumors. Due to its fundamental nature, in which energy is transmitted in pulses, the laser tip must be in contact or near contact with the tissue for effective ablation. Treatment can be hampered by undesired tissue adherence to the laser fiber, which ultimately reduces efficiency. In addition, hemostasis is not as good as with the Nd:YAG laser. In order to overcome some of these negatives, a combination of Ho:YAG and Nd:YAG laser was developed in the early 2000s, with both laser energies housed in 1 machine with a dual foot pedal and a single silica fiber capable of transmitting both energies, allowing for switching from one source of energy to the other for ablation and hemostasis, respectively.
Recent developments in holmium laser technology include high-powered lasers capable of 150 watts of energy and pulse modulation. High-powered holmium lasers permit pulse energies as high as 5 J and frequencies as high as 120 Hz. The potential benefit is a smoother ablation, but in reality, high frequencies are not critical for effective tissue ablation. Pulse modulation can also be used to selectively modify tumor treatment. In the authors’ experience, a short pulse mode can permit faster ablation of large volumes of relatively avascular tumors, with the downside of more bubble production and more bleeding. Switching to long pulse mode, however, in which the same energy per pulse is delivered over a longer duration, can be used for “spot coagulation” of specific bleeding vessels and can also aid in the treatment of more vascular tumors, albeit at the expense of decreased vaporization and more charring of tissue. More advanced pulse modulation techniques, in particular, “double bubble” technology, in which an initial pulse generates a vapor bubble and a second pulse is delivered through the vapor bubble, allow for more effective energy delivery to the targeted tissue with less retropulsion, which is very useful for treating kidney stones. In the authors’ experience, it also has a salutary effect on the treatment of tumors, allowing for faster tissue ablation while promoting better hemostasis compared to single pulse technology. Some examples of double bubble technology include the Moses from Lumenis Inc and the Virtual Basket from Quanta Inc. Despite all their benefits, high-power holmium lasers have some drawbacks, such as noise production, size, higher voltage requirements, and the need for large, water-based fans for cooling.
Thulium-based laser systems have gained prominence as a promising option for safer and more efficient tumor ablation. Proietti et al demonstrated in their ex vivo porcine model that, when compared to Ho:YAG, thulium:YAG (Tm:YAG) lasers, with their 2,010 nm of continuous wave energy delivery, create a shallower (0.2–0.4 mm) and smoother incision, with a larger coagulative area.4 These characteristics make it an ideal alternative for soft tissue ablation, especially in the context of limited anatomical space. However, one drawback observed in the literature is the relative degree of tissue carbonization and the generated layer of coagulative necrosis at the tumor base that may prevent complete tumor ablation and could potentially lead to increased cicatricial effects such as strictures.5 One recent advance in Tm:YAG laser technology is the ability to switch from continuous mode to pulsed mode, with the former being better for hemostasis and ablation and the latter for tissue separation and incision. In the pulsed mode, there is high peak power, allowing for tissue separation or “blast” effect, but with less heat generation due to the energy profile of Tm:YAG crystals compared to the heat generated by a thulium fiber laser (TFL). Examples of this type of laser are the Thulio laser from Dornier Inc and the Revolix laser from Lisa Lasers Inc.
In contradistinction to Tm:YAG, the new superpulsed TFLs have a pulsed diode energy source delivered through silica fibers doped with thulium ions, producing a laser beam with a wavelength of 1,940 nm. This wavelength is almost precisely at the peak absorption coefficient of water, allowing for enhanced tissue effects. Despite being in its infancy, based on initial experience, TFL demonstrates the positive characteristics of both Ho:YAG and Tm:YAG laser devices, namely effective and efficient tumor ablation, preserved hemostatic potential, limited tissue carbonization, and limited depth of penetration. Although the literature is currently limited, one recent retrospective study showed that TFL is a safe and effective laser technology for treating upper tract tumors in the short-term follow-up period without any significant complications.6 Other advantages of TFL systems are their smaller profile, lower voltage requirements, quiet performance, and smaller, lighter, air-based cooling fans. In our experience, the smaller 150 μm laser fibers of TFL systems allow for better irrigation and increased flexibility, permitting access to lower pole tumors without sacrificing ablation ability (possibly due to the better coherence of TFL laser beams compared to holmium). The TFL lasers also have a wider range of pulse energy and frequency, but in practical terms this does not provide a benefit for the purposes of tumor ablation. Two major advantages, however, are better hemostasis and tissue separation effects. This has permitted our center to perform en bloc enucleation of ureteral and renal pelvis tumors, similar to what is becoming popular for bladder tumors (see Figure). Although this is also possible with holmium laser systems, the hemostasis and, therefore, visualization is not as good.
Despite the advancements in laser technology and ureteroscopic equipment, there remains no substitute for surgeon expertise and meticulous technique. In our practice, a no-touch method is employed in which a flexible ureteroscope is advanced under direct visualization in a retrograde fashion without any guidewires or access sheaths into the ureteral orifice. The flexible scope is advanced slowly and meticulously up the ureter with minimal irrigation. This is particularly important when trying to lateralize hematuria. The culprit could be a very tiny carcinoma in situ lesion that would otherwise become obscured and impossible to find if a guidewire were placed prior to advancing the scope. Adjuvant visualization technologies such as Clara and Chroma (Storz Medical Inc) or Narrow Band Imaging (Olympus Medical Inc) can be invaluable for discovering these subtle lesions. A thorough mapping of the entire collecting system is performed. This is done even if a lesion in the ureter is discovered because missing a lesion in the kidney could affect management, especially when kidney-sparing treatment is being contemplated (whether local resection, segmental ureterectomy, or distal ureterectomy with reimplant). In addition, multifocality is a negative prognostic indicator, especially in endoscopic management. Finally, a saline barbotage for cytology in the vicinity of the lesion can be critical to finding high-grade disease, especially when biopsies come back nondiagnostic. Grading is paramount; therefore, every attempt should be made to obtain adequate biopsy samples. In this respect, the authors favor the use of the Piranha 3F biopsy forceps (Boston Scientific Inc) for flat lesions, nitinol or stainless-steel baskets for sessile lesions, forward opening graspers such as the Dakota (Boston Scientific Inc) or the N-Gage (Cook Medical Inc) for papillary lesions, and the BIGopsy backloaded trans-access sheath device (Cook Urological Inc) for nontangential intrarenal lesions. However, these ancillary devices tend to deform the urothelial architecture and cause unintended bleeding, leading to poor visibility and inadequate diagnostic assessment despite best efforts. If feasible, en bloc laser enucleation is the preferred approach when an endoscopic cure is being attempted. The primary benefits include a sufficient and representative pathological specimen, a reduction in tissue artifacts, and superior hemostasis.
Regarding laser choice, the authors favor the TFL for en bloc enucleation for most lesions, although we have used all 3 technologies for enucleation. In the authors’ experience, the Tm:YAG laser is a hybrid in terms of effect when compared to TFLs and Ho:YAG lasers, with better vaporization and less charring than TFL but less vaporization and more charring than Ho:YAG. These laser technologies are perfectly acceptable and reasonable for endoscopic management. Ultimately, the choice of laser boils down to availability, surgeon experience, and preference.
- Rouprêt M, Babjuk M, Burger M, et al. European Association of Urology guidelines on upper urinary tract urothelial carcinoma: 2020 update. Eur Urol. 2021;79(1):62-79.
- Browne BM, Stensland KD, Moynihan MJ, Canes D. An analysis of staging and treatment trends for upper tract urothelial carcinoma in the National Cancer Database. Clin Genitourin Cancer. 2018;16(4):e743-e750.
- Petros FG, Li R, Matin SF. Endoscopic approaches to upper tract urothelial carcinoma. Urol Clin North Am. 2018;45(2):267-286.
- Proietti S, Rodríguez-Socarrás ME, Eisner BH, et al. Thulium:AG versus holmium:YAG laser effect on upper urinary tract soft tissue: evidence from an ex vivo experimental study. J Endourol. 2021;35(4):544-551.
- Defidio L, Antonucci M, De Dominicis M, Fuchs G, Patel A. Thulium-holmium:YAG duo laser in conservative upper tract urothelial cancer treatment: 13 years experience from a tertiary national referral center. J Endourol. 2019;33(11):902-908.
- Proietti S, Johnston T, Pupulin M, et al. Effectiveness and safety of thulium fiber laser in the conservative management of patients with upper tract urothelial carcinoma. Eur Urol Open Sci. 2022;46:99-104.