World J Oncol

World Journal of Oncology, ISSN 1920-4531 print, 1920-454X online, Open Access

Article copyright, the authors; Journal compilation copyright, World J Oncol and Elmer Press Inc

Journal website https://www.wjon.org

Review

Volume 12, Number 1, February 2021, pages 20-27

Diagnostic and Therapeutic Challenges of Rare Urogenital Cancers: Urothelial Carcinoma of the Renal Pelvis, Ureters and Urethra

Figure 1. Imaging of upper urinary tract tumor. (a) CT urography showing suspicion zone of stenosis causing right unilateral hydroureteronephrosis. (b) Coronal view CT urography with filling defect in the proximal left ureters. (c) Ureteroscopy showing a non-obstructing tumor along mid ureters (white arrow showing the guidewire). CT: computed tomography.

**Table 1.** Available Guidelines and Summary of Clinical Presentations, Risk Factors and Diagnostics of Upper Tract Urothelial Carcinoma and Primary Urethral Cancer
Urothelial cancer	Available guidelines	Clinical presentation	Risk factors	Diagnosis and imaging	Staging
BOO: bladder outlet obstruction; CT: computed tomography; EAU: European Association of Urology; ESMO: European Society of Medical Oncology; MRI: magnetic resonance imaging; NCCN: National Comprehensive Cancer Network; STD: sexually transmitted disease; TMN: tumor-node-metastasis; UCF: urethrocutaneous fistula; WHO: World Health Organization.
Upper urinary tract urothelial carcinoma	EAU [2], ESMO [9], NCCN [10]	Early: hematuria flank pain Late: hematuria + obstructive urinary symptoms, lumbar mass [2, 9, 10]	Smoking, aristocholic acid, Chinese herbs, aromatic amines [2, 11-13]	Histopathology, CT urography, MRI urography, cystoscopy diagnostic ureteroscopy [2, 10, 14]	TNM classification [2], WHO tumor grade [2]
Primary urothelial carcinoma of the urethra	EAU [6], NCCN [10]	Early: hematuria + bloody urethra discharge Late: extra-urethral mass, BOO, pelvic pain, UCF, abscess, dyspareunia [6, 15]	Urethral stricture, chronic irritation, urethritis/STDs, recurrent UTI [6, 15]	Histopathology, urinary cytology, diagnostic urethrocystoscopy, MRI, CT scan [6, 10]	TNM classification [6], WHO tumor grade [6]

Table 1. Available Guidelines and Summary of Clinical Presentations, Risk Factors and Diagnostics of Upper Tract Urothelial Carcinoma and Primary Urethral Cancer

Urothelial cancer

Available guidelines

Clinical presentation

Risk factors

Diagnosis and imaging

Staging

BOO: bladder outlet obstruction; CT: computed tomography; EAU: European Association of Urology; ESMO: European Society of Medical Oncology; MRI: magnetic resonance imaging; NCCN: National Comprehensive Cancer Network; STD: sexually transmitted disease; TMN: tumor-node-metastasis; UCF: urethrocutaneous fistula; WHO: World Health Organization.

Upper urinary tract urothelial carcinoma

EAU [2], ESMO [9], NCCN [10]

Early: hematuria flank pain
Late: hematuria + obstructive urinary symptoms, lumbar mass [2, 9, 10]

Smoking, aristocholic acid, Chinese herbs, aromatic amines [2, 11-13]

Histopathology, CT urography, MRI urography, cystoscopy diagnostic ureteroscopy [2, 10, 14]

TNM classification [2], WHO tumor grade [2]

Primary urothelial carcinoma of the urethra

EAU [6], NCCN [10]

Early: hematuria + bloody urethra discharge
Late: extra-urethral mass, BOO, pelvic pain, UCF, abscess, dyspareunia [6, 15]

Urethral stricture, chronic irritation, urethritis/STDs, recurrent UTI [6, 15]

Histopathology, urinary cytology, diagnostic urethrocystoscopy, MRI, CT scan [6, 10]

TNM classification [6], WHO tumor grade [6]

**Table 2.** Summary of the Management, Prognostics and Outcome of Urothelial Cancer of the Upper Urinary Tract and Urethra
Urothelial cancer	Localized diseases	Locally advanced	Advanced and metastatic	Prognostic indicators	5-year specific survival	Follow-up
LND: lymph node dissection; RNU: radical nephroureterectomy; SCC: squamous cell carcinoma; T: tumor; UC: urothelial carcinoma; URS: ureteroscopy.
Renal calyx	Low risk: URS, RNU [2]; High risk: RNU + LND [2]	Multimodal: neoadjuvant chemotherapy for select patients + RNU + LND + adjuvant chemotherapy [2, 9, 10]	Systemic therapy extrapolated from bladder cancer treatment	Preoperative [2]: age/gender, ethnicity, tobacco, tumor location, surgical delay; Postoperative [2]: tumor stage/grade, lymph node status, lymphovascular invasion, surgical margin, histology	pT2/pT3 < 50% [2]; pT4 < 10% [2]	Follow-up is more often and rigorous in patients who have undergone kidney-sparing treatment compared to patients who had radical nephroureterectomy [2, 9, 10]
Renal pelvis	Low risk: URS, percutaneous [2]; High risk: RNU + LND [2]
Proximal and mid ureters	Low risk: URS [2], uretero-ureterostomy; High risk: RNU + LND [2]
Distal ureters	Low risk: URS [2], distal ureterectomy; High risk: RNU + LND [2]
Primary urothelial carcinoma of the urethra in males	Distal tumor: penile-preserving surgery; primary urethrectomy [6, 15]	Multimodal: neoadjuvant. chemotherapy (cisplatin-based) radiotherapy for SCC [6, 10, 15]		Age, race, tumor stage and grade, nodal stage, metastasis histology, tumor size, tumor location, concomitant bladder cancer type and modality of treatment [6, 10, 15]	The 5-year relative survival rate of primary UC of the urethra is 52% [6, 10, 15]	Despite limited data, it is practical to adhere stricter follow-up in patients undergoing urethra-sparing surgery, with urinary cytology, urethrocystoscopy and cross-sectional imaging [6, 10, 15]
Primary urothelial carcinoma of the urethra in females	Anterior tumor: urethral-sparing surgery [6, 10], primary urethrectomy [6, 15]	Multimodal: neoadjuvant. chemotherapy (cisplatin-based) radiotherapy for SCC [6, 10, 15]

Table 2. Summary of the Management, Prognostics and Outcome of Urothelial Cancer of the Upper Urinary Tract and Urethra

Urothelial cancer

Localized diseases

Locally advanced

Advanced and metastatic

Prognostic indicators

5-year specific survival

Follow-up

LND: lymph node dissection; RNU: radical nephroureterectomy; SCC: squamous cell carcinoma; T: tumor; UC: urothelial carcinoma; URS: ureteroscopy.

Renal calyx

Low risk: URS, RNU [2]; High risk: RNU + LND [2]

Multimodal: neoadjuvant chemotherapy for select patients + RNU + LND + adjuvant chemotherapy [2, 9, 10]

Systemic therapy extrapolated from bladder cancer treatment

Preoperative [2]: age/gender, ethnicity, tobacco, tumor location, surgical delay; Postoperative [2]: tumor stage/grade, lymph node status, lymphovascular invasion, surgical margin, histology

pT2/pT3 < 50% [2]; pT4 < 10% [2]

Follow-up is more often and rigorous in patients who have undergone kidney-sparing treatment compared to patients who had radical nephroureterectomy [2, 9, 10]

Renal pelvis

Low risk: URS, percutaneous [2]; High risk: RNU + LND [2]

Proximal and mid ureters

Low risk: URS [2], uretero-ureterostomy; High risk: RNU + LND [2]

Distal ureters

Low risk: URS [2], distal ureterectomy; High risk: RNU + LND [2]

Primary urothelial carcinoma of the urethra in males

Distal tumor: penile-preserving surgery; primary urethrectomy [6, 15]

Multimodal: neoadjuvant. chemotherapy (cisplatin-based) radiotherapy for SCC [6, 10, 15]

Age, race, tumor stage and grade, nodal stage, metastasis histology, tumor size, tumor location, concomitant bladder cancer type and modality of treatment [6, 10, 15]

The 5-year relative survival rate of primary UC of the urethra is 52% [6, 10, 15]

Despite limited data, it is practical to adhere stricter follow-up in patients undergoing urethra-sparing surgery, with urinary cytology, urethrocystoscopy and cross-sectional imaging [6, 10, 15]

Primary urothelial carcinoma of the urethra in females

Anterior tumor: urethral-sparing surgery [6, 10], primary urethrectomy [6, 15]

Multimodal: neoadjuvant. chemotherapy (cisplatin-based) radiotherapy for SCC [6, 10, 15]