Chemotherapy for Upper Tract Urothelial Carcinoma - A Complete Guide

Introduction

Urothelial carcinomas of the upper urinary tract (UTUCs) are uncommon and have a less favorable prognosis at each stage than urothelial carcinomas of the urinary bladder. The goal of the POUT (Perioperative chemotherapy versus surveillance in upper tract urothelial carcinoma) experiment was to evaluate the effectiveness of systemic platinum-based chemotherapy in patients with UTUCs.

What Is Chemotherapy?

Chemotherapy is a medical treatment that involves the use of drugs to kill or inhibit the growth of cancer cells. It refers to the administration of cytotoxic medications to eradicate cancer cells. It may be administered to mitigate the likelihood of cancer recurrence following a surgical procedure. Alternatively, it might be employed as the primary therapeutic approach for metastasizing cancer to distant anatomical sites.

What Is Upper Tract Urothelial Carcinoma?

Urothelial cancer is cancer of the walls of the urinary tract; it starts in the bladder. Upper tract urothelial cancers (UTUCs) are a type of urothelial cancer that starts in the renal pelvis (the lining of the kidney) or the ureter (the long, thin tube that connects the kidney to the bladder). However, UTUCs can block the ureter or kidney, which can lead to infections and swelling.

What Are the Various Signs and Symptoms?

Signs of UTUC may be discovered by accident or as a result of symptoms. In 20 to 32 percent of cases, flank pain is caused by a clot or tumor tissue blockage. Patients with UTUC who experience systemic symptoms such as:

• Anorexia.

• Weight loss.

• Malaise.

• Lethargy.

• Fever.

• Night sweats.

• Cough.

What Are the Various Causes and Risk Factors?

• Males are more likely, ranging from two to three times, to develop UTUC compared to females.

• This condition is predominantly observed in individuals aged 70 or above.

• Smoking is the most significant risk factor.

• Individuals with a hereditary disorder known as Lynch syndrome (it is a hereditary cancer syndrome characterized by an inherited susceptibility to several cancer forms.) are also more susceptible to the danger. This condition increases the likelihood of developing certain types of cancer, including UTUC.

What Is the Classification of UTUC?

• Low-Grade UTUC: It is less aggressive. Its probability of infiltrating further into the kidney or metastasizing to other body areas is reduced.

• High-Grade UTUC: Advanced UTUC is more likely to infiltrate the kidney or other organs and metastasize to different body regions.

The rates of cancer recurrence are elevated for both low-grade and high-grade tumors. Consequently, individuals diagnosed with any kind of UTUC should diligently seek regular medical evaluation, as there is a high probability of cancer recurrence post-treatment.

What Are the Various Diagnosis Methods?

Imaging Methods

1. Computed Tomography:

• It is also known as a CT scan, a medical imaging technique that uses X-rays and computer processing to create detailed cross-sectional images of the body.

• CT urography is the most accurate diagnostic imaging technology available.

• The quick capture of thin sections enables the creation of high-resolution isotropic pictures that may be seen from various angles to aid in diagnosis without any reduction in quality. CT scans typically do not show epithelial "flat lesions" that do not cause any changes in the shape or thickness of the urothelium.

• Enlarged lymph nodes shown on CT scans are strongly indicative of metastases in upper tract urothelial carcinoma (UTUC).

2. Magnetic Resonance Urography:

• Magnetic resonance (MR) urography is a medical imaging technique recommended for patients who cannot undergo CT urography, typically due to contraindications to radiation or iodinated contrast material.

• After the contrast administration, MR urography's sensitivity for detecting tumors is smaller.

• Computed tomography urography is superior to MR urography's sensitivity and specificity for diagnosing and staging UTUC.

3. F-Fluorodeoxyglucose Positron Emission Tomography and Computed Tomography:

• FDG-PET/CT scans of 18F-fluorodeoxyglucose positron emission tomography are used in UTUC patients who have had surgery.

• It shows that lymph nodes thought to be suspicious were linked to a lower rate of recurrence-free death.

• It is also possible to use FDG-PET to look at distant and nodal tumors in people who should not receive iodinated contrast because they are allergic or have kidney problems.

4. Cytology:

• Abnormal cytology can indicate high-grade upper tract urothelial carcinoma (UTUC) when bladder cystoscopy seems normal and carcinoma in situ (CIS) is absent in the bladder and prostatic urethra.

• Obtaining cytology from the diseased upper tract is more sensitive for detecting upper tract urothelial carcinoma (UTUC) than voided urine cytology.

5. Ureteroscopy:

• Flexible ureteroscopy (URS) is employed to verify a diagnosis of UTUC by examining the ureter, renal pelvis, and collecting system and extracting a biopsy of any lesions. Ultrasound imaging can provide information on a tumor's presence, appearance, multilocality, and size.

• Ureteroscopic biopsies have a diagnostic accuracy of over 90 percent in determining the grade of a tumor, with a low incidence of false-negative results. Nevertheless, ureteroscopic diagnostic biopsy specimens are inferior to nephroureterectomy specimens, thus necessitating a second-look URS as a follow-up component if kidney-sparing treatment is opted for.

• Integrating the biopsy grade with imaging results and urinary cytology can assist physicians in determining whether to proceed with radical nephroureterectomy (RNU) or kidney-sparing treatment.

• A biopsy during a URS procedure heightened the likelihood of an intravesical recurrence.

• Advancements in flexible ureteroscopes and the utilization of novel imaging techniques can enhance visibility and facilitate the detection of flat tumors. The potential utility of narrow-band imaging is promising, though the findings are now in their preliminary stages.

What Is the Chemotherapy Treatment?

UTUC, or upper tract urothelial carcinoma, is an uncommon type of cancer; they are associated with varied histology and are exceptionally rare. Variant histology refers to abnormal or atypical cellular characteristics within a tissue sample.

• UTUC, or upper tract urothelial carcinoma, has a notable adverse prognostic factor that affects multiple aspects of survival in individuals with UTUC.

• Therefore, vUTUC acts as a preventive and anticipatory indicator that may require early systemic therapy, usually chemotherapy, either before or after RNU for UTUC.

• Administering chemotherapy during the perioperative period, either before (neoadjuvant) or after (adjuvant) surgery, has been proven to improve the survival rates of patients with upper tract urothelial carcinoma (UTUC).

• Perioperative chemotherapy is beneficial in several forms of bladder UC.

• Systemic chemotherapy involves the delivery of medications that can circulate throughout the entire body to treat cancer.

• UTUC (upper tract urothelial cancer) and bladder UC (urothelial carcinoma) have comparable histology and prognostic characteristics; the chemotherapy treatment for UTUC often follows the standard regimen for bladder urothelial cancer.

• Hence, most urologists or oncologists adapt conventional chemotherapy regimens for bladder UC to address vUTUC.

• They have a cystectomy, followed by administering neoadjuvant chemotherapy, which leads to a general enhancement in survival rates for patients with variant bladder UC.

• Chemotherapy has a specific and significant role in the treatment of bladder urothelial carcinoma with different histological variants.

• Hence, the current Cisplatin chemotherapy regimen holds promise for effectively treating urothelial carcinoma with diverse histological characteristics, including UTUC.

• Adjuvant chemotherapy offers a survival advantage for individuals with pure UTUC but does not provide the same benefit for those with UTUC variants.

• A lymphadenectomy has been suggested in RNU for UTUC because it might help the patient live longer.

Conclusion

Upper tract urothelial carcinoma has not migrated to other regions of the body; it is usually diagnosed as a locally progressed illness. The prognosis for this type of sickness is poor because it frequently recurs in other places of the body. Upper and lower tract urothelial malignancies are treated differently, but the illnesses are often identical. Neoadjuvant chemotherapy is the standard of care in this area because it has been proven to improve survival in well-conducted phase III trials. There is no evidence available about adjuvant treatment for bladder cancer, and it is difficult to administer Cisplatin-based regimens to patients who may have decreased kidney function following a nephrectomy, making adjuvant therapy for upper tract illness much more problematic. As a result, until further research is conducted, the best treatment for locally progressed upper tract urothelial carcinoma is Cisplatin-based neoadjuvant chemotherapy followed by a nephrectomy and surgical resection.