Urethral neuroendocrine tumors (UNETs) are classified as a rare and particularly aggressive subset of tumors that develop in the urethra. Protheragen provides an integrated service portfolio focused on diagnosis and therapy development for UNET. Our specialists utilize the latest technologies alongside their detailed knowledge of UNET biology to develop new and effective approaches.
Overview of Urethral Neuroendocrine Tumor
Urethral neuroendocrine tumors (UNETs) emerge from neuroendocrine cells situated in the urethra, classified as an uncommon and extremely aggressive tumor of neuroendocrine origin. The tumors are made of small, round, and high-grade malignant cells with neuroendocrine differentiation. Hormones and peptide signals are produced by neuroendocrine tumors. Unlike more common forms of urethral neoplasms, such as squamous cell carcinoma or transitional cell carcinoma, neuroendocrine tumors of the urethra are extremely difficult to manage from both the diagnostic and therapeutic perspectives. Although relatively uncommon, such tumors have attracted considerable clinical attention and research efforts due to their aggressive behavior and propensity to metastasize to other organs.
Fig.1 Pathological analysis of urethral neuroendocrine tumor cases. (Miki K.,
et al., 2023)
Pathogenesis of Urethral Neuroendocrine Tumor
The development of urethral neuroendocrine tumors involves various causes, such as specific genetic alterations, being subjected to carcinogenic substances, as well as having certain underlying urological conditions. These tumors form through a primary pathway of changing multipotent epithelial cells within the transitional epithelium. These cells can undergo a certain change to neuroendocrine cells, which gives rise to UNETs. Also, certain carcinogenic substances, particularly cigarette smoke, can cause some genetic alterations to tumors. Sometimes the existence of carcinoma in situ (CIS) in the bladder neck or prostatic urethra has been linked to the later development of UNETs. This indicates that CIS can act as a precursor lesion, making the body susceptible to changes that lead to neuroendocrine differentiation. Moreover, the co-occurrence of UNETs with different histological elements, such as urothelial carcinoma, bolsters the hypothesis of shared clonal divergence from multipotential cells, including cancer stem cells.
Diagnostics Development for Urethral Neuroendocrine Tumor
- Histopathological Examination
The diagnosis of urethral neuroendocrine tumors still relies on histopathological analysis as the gold standard. Examination of biopsy slides reveals peculiar features, which include small, round or even spindle-shaped cells that display a high degree of mitotic activity. To confirm the diagnosis of the tumor's neuroendocrine features, Secondary staining using immunohistochemistry is necessary. To differentiate UNETs from other urethral malignancies, immunohistochemistry using synaptophysin, CD56, and chromogranin A is done.
- Cytological Analysis
The diagnosis of UNETs can also be assisted by the cytological examination of urine samples or urethral washings. Urethral washing cytology is capable of detecting malignant cells, which can signal the recurrence of a tumor. This technique is specifically non-invasive, which is an advantage in the follow-up of patients who have a history of bladder cancer or previous urethral malignancies. In one reported case, cytological analysis revealing malignant cells resulted in the diagnosis of urethral recurrence of bladder cancer with neuroendocrine differentiation.
Therapeutics Development for Urethral Neuroendocrine Tumor
To reduce the risk of recurrence and enhance survival outcomes for patients with urethral neuroendocrine tumors, the use of adjuvant chemotherapy is often suggested. Etoposide and cisplatin are two commonly used drugs in chemotherapy and are effective for neuroendocrine tumors. For example, there was a documented case of male urethral small cell carcinoma that had significant survival benefits and metastasis, which was managed with adjuvant cisplatin chemotherapy. Even so, the efficacy of adjuvant therapy in UNETs is still not fully understood owing to the small number of documented cases.
Table 1. Therapeutics of Urethral Neuroendocrine Tumor.
| Therapeutics |
Drug Name |
Mechanism |
Description |
Stage |
| Surgical Intervention |
Partial Penectomy |
Physical removal of the tumor |
Surgical removal of the tumor, often combined with partial penectomy to ensure complete resection. |
Approved |
| Surgical Intervention |
Urethrectomy |
Physical removal of the tumor |
Complete or partial removal of the urethra to eliminate the tumor. |
Approved |
| Adjuvant Chemotherapy |
Etoposide |
Inhibition of topoisomerase II, leading to DNA damage and cell death |
Used in combination with cisplatin to treat neuroendocrine tumors by disrupting DNA replication. |
Approved |
| Adjuvant Chemotherapy |
Cisplatin |
Formation of DNA adducts, leading to apoptosis |
A platinum-based chemotherapy agent that induces DNA damage and inhibits cell division. |
Approved |
| Radiation Therapy |
N/A |
Ionizing radiation to kill cancer cells |
Used to target residual disease or as palliative care for advanced tumors. |
Approved |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
Our Services
Protheragen stands out in the field of UNET diagnostics and therapeutics development due to our deep expertise, cutting-edge technologies, and collaborative approach. We have established partnerships with leading academic institutions and research organizations, enabling us to access a vast network of resources and knowledge. This collaborative ecosystem, combined with our internal capabilities, positions us as a leader in the development of innovative solutions for UNET.
Recognizing the unique needs of each project, Protheragen offers customized services tailored to specific research objectives. Whether it's the development of a novel diagnostic assay or the optimization of a therapeutic regimen, our team works closely with clients to design and execute studies that meet their exact requirements. If you are interested in our services, please feel free to contact us.
References
- Miki, Koji, et al. "A case of neuroendocrine tumor at the external urethral meatus after total cystectomy." IJU Case Reports 6.6 (2023): 424-427.
- Murata, Yasuaki, et al. "Recurrent urethral tumor with neuroendocrine differentiation in a female patient after radical cystectomy for bladder cancer." IJU Case Reports 6.4 (2023): 199.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.
