UCC is a common tumor in developed countries, and its incidence ranks fourth[7]. It can be divided into a lower urinary tract (bladder and urethra) and UTUC (renal pelvis cavity and ureter). Bladder cancer accounts for 90–95% of UCC[8]. The incidence of UTUC is lower than that of bladder cancer.
The best treatment for UTUC is surgical resection, including renal ureterectomy+bladder sleeve resection and kidney-retaining surgery. The choice of surgical plan depends on whether the tumor is at high risk[9], tumor >2 cm, multiple tumors, hydronephrosis, exfoliative cytology for HG, urethroscopy for HG, previous history of radical operation of bladder cancer, histologic variation, etc. If any of them are high risk, radical surgery should be opted. UTUC has the characteristics of complex heterogeneity, multicenter, and strong invasiveness. If renal pelvis carcinoma is resected only by kidney and partial ureter, the incidence of residual ureter tumor can be higher[10]. Therefore, renal ureterectomy+bladder sleeve resection is the gold standard for the treatment of UTUC [11]. The grading and staging of UTUC is not related to the presence or absence of symptoms. In fact, asymptomatic UTUC is also a tumor with HG stage, so radical surgery is recommended. In our study, 121 cases underwent radical full-length renal ureterectomy+bladder sleeve resection. Among them, the main treatment was surgical treatment, including 64 cases of open radical resection of renal pelvis/ureter carcinoma and 57 cases of laparoscopic radical resection of renal pelvis/ureter carcinoma, and a small number of cases had kidney-retaining surgery.
In this study, 95.24% (20 / 21) of asymptomatic UTUC group and 30.43% (35 / 115) of symptomatic UTUC group underwent preoperative or intraoperative examination of rigid/flexible ureteroscope biopsy. All of them were confirmed to be suffering from UCC. The reasons for the difference in the proportion of biopsies between the two groups are as follows: (1) The diagnosis of asymptomatic UTUC patients lacks the support of typical symptoms. We need more accurate examination to clarify the nature of space occupation to determine the surgical scheme and avoid excessive treatment; (2) some asymptomatic UTUC patients lack the evidence of typical malignant tumors before operation; (3) avoid medical disputes. The results show that most asymptomatic UTUC cases were HG and high stage UCC, not significantly different from symptomatic UTUC cases.
Notably, the rigid/flexible ureteroscope biopsy cannot provide deep or full-thickness specimens due to the superficial appearance. They can only be diagnosed by grade and cannot be staged accurately, and some patients may be underestimated[12]. In this study, five cases with upper urinary tract tumors underwent preoperative/intraoperative pathological biopsies with moderate differentiation (G2). Therefore, two cases underwent holmium laser resection of renal pelvis tumors under a flexible ureteroscope. The pathological changes were upgraded to HG (G3) after the operation. Tumor recurrence occurred within one year, and final death occurred within two years. The other three cases were treated by radical operation. Among them, one case was pathologically upgraded to HG (G3) after the operation, and no recurrence was found in three patients who were followed up for two years.
In addition, the holmium laser resection of tumor may cause the burning and destruction of surgical specimens, which may affect the accuracy of postoperative pathology. Therefore, patients with moderately differentiated (G2) renal pelvis tumors undergoing holmium laser resection under a soft microscope should be vigilant. They should be followed-up closely, and radical surgery should be performed if necessary.
In our previous study of asymptomatic bladder tumors, we found that most of asymptomatic bladder urothelial carcinoma could be resected through urethra without radical surgery[5].In clinical study, some patients may have asymptomatic UTUC and asymptomatic bladder cancer; in the choice of surgical methods, doctors are more inclined to conduct kidney surgery. However, we found that the stage and grade of UTUC were not related to the presence of symptoms. Although this and bladder cancer were both the sources of urinary epithelial, but the pathological stage and grade were higher. Therefore, asymptomatic UTUC patients should be risk stratified according to the clinical stage classification and other parameters and select the corresponding surgical treatment method. The treatment principle and symptomatic UTUC should be the same; radical operation is still the golden standard of treatment. Conservative surgery can be considered with informed consent for patients with old and weak, poor tolerance to surgery, isolated kidney, etc.
Upper urinary urothelial carcinoma has the characteristics of multicentric growth and easy shedding implantation. The incidence of bladder tumor after UTUC is as high as 22–47%[13]. The high recurrence rate of bladder tumor severely affects the quality of life and threatens the life and health of patients. Therefore, how to reduce the recurrence rate of bladder tumor after UTUC is also a concern of urologists. Intravesical infusion chemotherapy after UTUC is mainly based on the choice of postoperative infusion chemotherapy for bladder urothelial carcinoma. However, at present, there is no consensus on the frequency and maintenance time of bladder perfusion after UTUC[14]. Although the morphology of UTUC is the same as that of bladder urothelial carcinoma, studies have shown some differences in biological characteristics and related gene expression[15, 16]. EUA guidelines recommend that UTUC should be treated with single intravesical infusion chemotherapy immediately after the radical resection of pyelopelvic carcinoma, which can reduce the risk of recurrence of bladder tumor in the first year after resection. At present, not much evidence is available for multiple perfusion. Some studies have shown that 6-8 times of intravesical infusion chemotherapy weekly may further reduce the risk of bladder recurrence[17]. High-quality evidence-based medical evidence is still needed to study the difference between single and multiple efficacy. In view of the higher pathological stage and grade of UTUC than bladder cancer, intravesical perfusion therapy was regularly conducted with standardized and full course of treatment after the operation. For high-risk upper urinary tract tumors with T3/T4 stage or lymph node metastasis after UTUC, platinum-based adjuvant chemotherapy is recommended, while paclitaxel or gemcitabine chemotherapy can be considered in patients with renal insufficiency. The latest stage 3 randomized controlled clinical study showed that the survival time of patients with UTUC treated with gemcitabine combined with cisplatin was significantly better than that of the control group after the operation, further indicating that chemotherapy could reduce the risk of tumor recurrence and prolong the life of patients[18]. Asymptomatic UTUC should also select the corresponding adjuvant treatment according to its stage and grade.
Compared with asymptomatic bladder cancer, asymptomatic UTUC is more malignant and more aggressive. However, compared with symptomatic UTUC, asymptomatic UTUC does not show a lower grade of staging and should be taken seriously. The principle of asymptomatic UTUC treatment is the same as that of symptomatic UTUC. Risk stratification should be carried out according to clinical staging and other parameters, and the corresponding surgical treatment should be selected.