The Evolving Treatment Landscape of Low-grade Upper Tract Urothelial Carcinoma

EP. 1A: Key Considerations in the Diagnosis and Treatment of Upper Tract Urothelial Carcinoma

In the first video of the series, Jennifer A. Linehan, MD, provides an overview of LG-UTUC including risk factors, signs and symptoms, and diagnosis as well as factors to consider regarding disease progression, recurrence, and which patients might be candidates for resection.



[One of] the most common risk factors for low-grade [upper tract] urothelial carcinoma (LG UTUC) [is] a history of bladder cancer, either low- or high-grade. Patients [who] have known Lynch syndrome have a risk of low-grade UTUC. Patients who are smokers, have a history of smoking, or [have other] risk factors such as exposure to aniline dyes [or] aristolochic acid exposure over time [are at-risk]. Patients who may be working with certain chemicals such as chemicals you would stain wood with or paints or those types of exposures [are also at-risk].

When you're examining patients and have them undergoing imaging, you may be looking in the bladder, up in the kidney, [or] up in the ureter. Any patients [who] have very large tumors, especially tumors greater than 2 cm; patients [who] have characteristics of the tumor invading the kidney or surrounding tissues on imaging; patients [who] have lymphadenopathy and large lymph nodes—even though it's within the pelvis near the bladder—[all have] signs to me that this could be a high-grade versus a low-grade cancer. From a molecular perspective, patients [who] have higher-grade disease have a higher predisposition [to] the FGFR mutation.

Most of my patients with low-grade UTUC have presented with hydronephrosis on imaging and microscopic hematuria. Occasionally, I will also see gross, painless hematuria. Some patients will just come in with flank pain, and obviously, there'll be abnormalities on imaging that will lead me into that diagnosis. Then, of course, we perform ureteroscopy and find if it's low-grade or high-grade.

In my practice in diagnosing low-grade UTUC, I usually get imaging with the CT (computed tomography) urogram. You can also do MR (magnetic resonance) urogram. I think both are equally good, depending on your institution. I do urine cytology in the clinic; [however], for upper tract disease, especially if it's low-grade, the value of finding something is probably minimal. I think urinalysis is always important. You want to see how much microscopic hematuria is there. Then, of course, [for] any patients [who] can't have contrast for whatever reason, [such as] renal function or contrast allergy, I think retrograde pyelogram is always a good test to see if there's a filling defect within the collecting system.

Every urologist is always worried about missing some high-grade urothelial carcinoma in the tumor as well. I think making the diagnosis is most important. I always tell my patients that they have to understand that—even when there is no high-grade disease, even with low-grade UTUC—the risk of recurrence is high.

[It is important to] understand that the recurrence rate is high; that while these cancers may not be dangerous in the setting of metastasis, they can harbor higher-grade cancers that we may not have found yet; and that the work-up is probably the most important combining pathology with biopsies as well as cytology when I'm doing ureteroscopy.

The cancer [may be] undertreated, these patients are 100% going to recur. The tumor can grow, and if left untreated, that can flourish into high-grade disease.

Concerning recurrence as well as progression of low-grade UTUC, recurrence is clearly my biggest concern. In patients, [I] make sure that I've adequately treated the tumors that are there. I know these patients [who have tumors with] a high likelihood [of recurring], so I'm going to monitor them closely, perhaps even do ureteroscopy every 3 months to make sure I've treated the tumor if I'm not using surgery plus some adjuvant treatment. As far as progression, I base that on the size. If I see very large tumors up in the collecting system, even if my biopsies are negative, if the tumors are greater than 2 cm, [such as] 3 or 4 cm, I'm always concerned that these could be harboring some high-grade disease.

For patients [who] have smaller tumors that are sitting in the ureter or sitting in the collecting system, especially if they're under 1 cm, there's a very low risk of progression to high-grade disease.

When I classify tumors of the upper tract as resectable versus nonresectable, I think of that in 2 settings. I think of the patients who have low-grade disease who have larger tumors or tumors in areas of the kidney or the ureter that I can't completely resect. Then I also think of patients with high-grade disease where the tumors may be extensively outside the kidney, invading other organs and even perhaps have some lymph node involvement. In this setting, if we're talking specifically about low-grade [disease], those are tumors that are in the area of the kidney where I just may not be able to get my flexible ureteroscope, where I may not be able to laser, where I may not be sure that I've taken care of everything. [The] tumors may [also] be [too] large. [If] I go in, do ureteroscopy, start to remove the tumor [with the] laser, and all of a sudden, it's getting really bloody, [and] I can't see anymore, [then] I have to come back another day. If I come back to treat a tumor 1, 2, [or] 3 times, those are the patients [for whom] I'm really worried that I'm dealing with more unresectable disease.

Transcript has been edited for clarity.