Of all the urological cancers, primary urethral cancer (PUC) is one of the rarest occurring malignancies (cancers). PUC accounts for less than 1% of all cancers.

The urethra is the duct that connects the meatus (opening) of the penis/vagina to the bladder. It is the final “pipe” in our plumbing that drains urine from the bladder.

The male and female urethra differ in length.  An average male urethra measures +/- 21cm in length and the average female urethra is +/- 4cm in length. 

The male urethra incorporates the prostate gland, situated just below the bladder. The mucosal membrane that lines the urethra is composed of transitional epithelium at the bladder and progressively changes along the urethra to squamous epithelium.

The image below depicts a diagram of both the male and female lower urinary tract, with the respective urethras highlighted in blue.

Male female urethral diagram
Simple diagram depicting the male and female urethra

There are three main subtypes of PUC, which are; urothelial carcinoma (UC), squamous cell carcinoma (SCC) and lastly adenocarcinoma (AC). Men commonly develop UC, followed by SCC and AC; whereas, AC is the most common in women followed by SCC and UC.

Risk Factors

Risk factors for developing PUC are similar between males and females; however, females arguably have more factors placing them at risk than males do.

  • History of bladder cancer
  • Chronic inflammation
  • Caruncles (Of the urethral opening)
  • Leukoplakia (Of the genitalia)
  • Urological trauma
  • Frequent urinary tract infections (UTI’s)
  • Sexually transmitted diseases (STD’s)
  • Human Papilloma Virus (HPV)
  • Sexual activity
  • Diverticula
  • Child birth
  • Being 60 years of age and older
  • History of bladder cancer
  • Urethral stricture
  • Chronic inflammation
  • Sexually transmitted diseases (STD’s)
  • Human Papilloma Virus (HPV)
  • Urological trauma
  • Sexual activity
  • Being 60 years of age and older


Certain symptoms of PUC will be shared by both men and women; however structural differences in genital anatomy mean that certain symptoms pertain only to men or women respectively.

  • Bleeding from the urethra
  • Blood in the urine
  • Frequent urination
  • Enlarged lymph nodes in groin
  • Weak and/or interrupted flow of urine
  • Frequent and/or urgent bowel movements
  • Discharge from the urethra (can be foul smelling or contain pus)
  • Urinary retention
  • Lump or thickness in the perineum or penis
  • Painful and/or uncomfortable intercourse
  • Priapism (persistent and painful erection)
  • Pain and/or swelling in the urethra, suprapubic region or the perineum)


As is standard with all cancerous tumours, early detection provides patients with the best possibility of cure. PUC is notoriously difficult to diagnose which is why your doctor will perform multiple diagnostic tests if they suspect you have PUC. In order to accurately diagnose and stage PUC, doctors will use a combination of the following:

four different diagnoses modalities wheel chart

Physical Examination


Early detection and evaluation normally occurs during a thorough physical examination. This should include the meticulous examination of the genitalia and rectum.The examination of male patients should include palpation of the entire urethra and perineum.

Care should be taken to palpate regional lymph nodes; enlarged lymph nodes may need to be surgically removed in the event of a cancer diagnosis. The discovery of the presence of fistula on the perineum may be indicative of advanced stage PUC.

Laboratory Studies

Lab studies refer to blood, urine and other specimen testing. These studies are unable to provide doctors with a definitive answer and/or diagnosis for suspected PUC patients. However, results from blood and urine analysis can help doctors rule out symptom suggested issues such as urinary tract infection. Results from various blood tests such as liver function tests can be a good indicator as to whether or not there is metastasis.

Imaging Studies

Magnetic Resonance Imaging (MRI) scans provide doctors with a comprehensive view of the human body that cannot be achieved by alternative imaging techniques. This wealth of visual data helps expedite the process of diagnosis, staging and treatment planning.

In addition to diagnostic capabilities, MRI scans afford doctors the ability to evaluate whether or not chemotherapeutic/radiation treatment is helping to shrink cancerous tumours.


The only way to definitively diagnose and stage PUC is through a transurethral (via the urethra) biopsy. In order to obtain a biopsy specimen, a small piece of tissue is removed from the suspected cancerous area. After the tissue sample is harvested, the specimen is sent for laboratory testing and examination. Lab technicians will examine the sample in order to establish the presence of malignant cells, the stage and type of cancer.

Keep in mind…

The rarity of this cancer and its ability to evade detection mean that PUC often goes undiagnosed until the disease has progressed into the advanced stages. In order to afford patients the best survival outcome and chance of cure, it is paramount that cancers like PUC are detected and diagnosed earlier rather than later.


Unfortunately, the low frequency at which PUC occurs means that modern medicine has yet to definitively establish the gold standard in terms of an appropriate treatment regime to combat this particular cancer.

The stage and location of the tumour will determine the treatment approach taken by doctors.

Current approaches taken to treat PUC include; multimodal therapies, radical surgery and regional lymphadenectomy (removal of lymph nodes). 

List of Treatments & Descriptions


Radiotherapies for PUC would include external beam radiation (EBR) and/or brachytherapy. Radiation therapy has been used as the only treatment modality for advanced stages of PUC in the past; however, radiation therapy most commonly used in conjunction with chemotherapy and/or surgery, forming the multimodal approach.



In the majority of PUC cases, chemotherapy has played a role in the treatment plan. An exact combination of chemotherapeutic agents has yet to be established to best combat PUC; however, depending on the type of cancer (SCC, AC or UC) usually a combination of three of the following agents has shown promising results in previous PUC patients; cisplatin, gemcitabine, ifosfamide, 5-fluorouracil, methotrexate, vinblastine and doxorubicin. 

Surgical Treatment

Depending on the size, location and depth of the tumour, surgical approaches to treating PUC include the following: partial or total penectomy (surgical removal of the penis), transurethral resection or urethrectomy (surgical removal of the urethra). 

For improved emotional and psychological outcomes in males, penile preservation is always of the utmost importance. However, in the case of metastatic or advanced PUC, survival often depends on the total removal of the penis.

Surgical approaches for women diagnosed with PUC often include partial or radical urethrectomy. When possible, partial urethrectomy is preferred in order to preserve urethral integrity.

In order to preserve penile function/length and urethral structure in both men and women; doctors must always consider and allow for  reconstructive surgery when opting for radical surgical treatment.

In the event of regional lymph gland involvement, your doctor will most likely need to perform what is called lymphadenectomy. This entails the removal of lymph glands that have been invaded by cancer.

Multimodal Therapy

Multimodal therapy – Multimodal therapies form the standard treatment approach taken by doctors treating PUC. Doctors have found that a multimodal approach affords patients the best chance of long term survival without disease recurrence. Multimodal therapies consist of a combination of the following, chemotherapy, radiation therapy and/or surgery.


Advanced stage PUC is commonly associated with metastasis (Tumour spread). The following sites are often the first to be invaded: prostate, bone and/or lymph nodes. In this event, the patient will require a multidisciplinary treatment approach. Depending on the site and extent of metastasis, this could include any of the following fields:  radiologists, urologists, orthopaedics, gynaecologists, radiation oncologists and oncologists.


There is no guaranteed way of ensuring that one does not develop cancer at some point in their life. However, there are measures one can take in order to reduce their over all risk of developing cancer. The following pertains particularly to PUC:

  • Reduce exposure to aromatic amines
  • Vaccinate yourself against HPV
  • Do not abuse pain killers
  • Regular self examination
  • Practice safe sex
  • Stop smoking


Epithelium/Epithelial – This refers to the thin layer of tissue that makes up the lining/surface of an internal or external organ.

Transitional cell epithelium – These are the cells that make up the structures of the urinary system. These cells have the ability to change shape and stretch without breaking or sustaining damage.

Squamous cell epithelium – These are epithelial cells that get their name from their distinct flat and scale-like shape. 

Radical surgery – The complete surgical removal of an organ or body part.

Transurethral – via the urethra.

Diverticula – Abnormal sac or pouch formation in a weak point in the wall of an alimentary tract.

The above article has been compiled using medical research and study outcomes, it is intended to be taken as guidance only. This article should not replace the advice or instruction of a medical practitioner.

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