Based on PubMed | Can melanoma or its treatments lead to blood in the urine, and how is this symptom evaluated?

Blood in the urine (hematuria) can be linked to melanoma in a few specific ways, and it can also occur as a side effect of certain melanoma treatments. It is important to evaluate hematuria promptly and systematically to determine the cause and guide management.

How Melanoma Can Cause Hematuria

• Bladder metastasis from melanoma: Although rare, melanoma can spread (metastasize) to the urinary bladder and present with visible blood in the urine and sometimes clots or urinary obstruction. Case reports describe gross hematuria due to solitary bladder tumors proven to be metastatic melanoma on cystoscopy and pathology. ^[1] In these reports, patients had prior cutaneous melanoma and later developed bladder lesions causing bleeding; outcomes varied and may be serious. ^[1] Metastatic bladder tumors overall are uncommon, but melanoma is among the primary cancers reported to metastasize there, and hematuria is a typical presenting sign when it does. ^[2]

• Other urinary tract involvement: Melanoma can rarely involve other parts of the urinary tract, but bladder involvement is the most documented in relation to hematuria. ^[1] When melanoma is known or suspected, any new hematuria warrants consideration of urinary tract metastasis along with more common causes. ^[2]

How Melanoma Treatments Can Cause Hematuria

• Immune checkpoint inhibitors (ICI): Drugs such as nivolumab and pembrolizumab can affect the kidneys and urinary tract through immune-related adverse events (e.g., interstitial nephritis or cystitis), which may lead to urinary symptoms including blood in the urine. Patient information and drug labeling note that these therapies may cause kidney damage with symptoms such as reduced urination and hematuria, and they recommend regular blood testing to monitor kidney function. ^[3] Similar advisories exist for nivolumab in various melanoma settings, highlighting hematuria as a possible side effect. ^[4] Hematuria is also listed among renal and urinary adverse events for pembrolizumab in official drug information. ^[5] Hematuria appears among reported adverse reactions in pembrolizumab safety data summaries. ^[6]

• Combination ICI (ipilimumab + nivolumab): Combined therapy can have broader immune-related effects, including rare but serious blood problems where hematuria may occur as part of bleeding manifestations. ^[7] Guidance for these regimens emphasizes seeking care for uncontrolled symptoms and monitoring for blood-related side effects such as blood in urine. ^[7]

• Targeted therapies (BRAF/MEK inhibitors): Trametinib (MEK inhibitor), often used with dabrafenib (BRAF inhibitor), has bleeding events documented across multiple sites, including hematuria and urinary bladder hemorrhage. ^[8] Safety materials for dabrafenib plus trametinib advise urgent attention to signs of bleeding such as blood in urine. ^[9] Hemorrhagic events can be serious, and monitoring for bleeding symptoms is recommended during treatment. ^[10] Hematuria is included among reported hemorrhage-related adverse events with trametinib. ^[11]

Initial Red Flags and When to Seek Care

• Visible (gross) hematuria: Painless, visible blood in urine should be investigated promptly because tumors of the urinary tract including bladder cancer or metastasis must be ruled out. ^[12] Gross hematuria often requires urgent, structured evaluation and specialist referral. ^[12]

• Symptoms suggesting kidney involvement: Decreased urination, flank pain, fever, or rising creatinine during ICI therapy can signal immune-related kidney issues and should lead to immediate contact with the oncology team. ^[3] Hematuria with treatment should prompt assessment and may necessitate pausing therapy and starting steroids if immune-mediated toxicity is suspected. ^[4]

How Hematuria Is Evaluated

Evaluation aims to confirm true hematuria, identify the source (kidney, ureter, bladder, urethra), and distinguish benign from serious causes.

• Confirm hematuria: Clinicians first verify that blood is truly present in urine and consider benign or spurious causes (e.g., menstruation, foods, exercise). ^[13] A focused history determines timing, associated pain, clots, and medication exposure (e.g., anticoagulants, ICIs, targeted agents). ^[14]

• Risk-based urologic workup: Modern guidance recommends tailoring the evaluation to the individual’s cancer risk. For those with high-risk features (age ≥60, heavy smoking history, many red blood cells on microscopy, or any gross hematuria), cystoscopy and CT urography are advised to assess for bladder and upper tract pathology. ^[15] Microscopic hematuria may warrant repeat urinalysis, urine culture, and kidney ultrasound, with escalation depending on persistence and risk factors. ^[16]

• Laboratory testing: Urinalysis, urine culture, and urine cytology can help differentiate infection, glomerular disease, or urothelial lesions; blood tests may include creatinine and coagulation studies when bleeding risk is suspected. ^[17] Workup strategies vary, but a problem-based algorithm considers the likelihood of urothelial cancer and selects imaging accordingly. ^[18]

• Imaging and cystoscopy: Cystoscopy visualizes the bladder directly to detect tumors, stones, or inflammation; CT urography evaluates kidneys and ureters for stones, masses, or bleeding sources. ^[12] In the context of melanoma, cystoscopy can identify atypical lesions that might represent metastasis, guiding biopsy and pathology confirmation. ^[1]

---

Practical Steps if You Have Hematuria During Melanoma Care

• Notify your oncology team promptly: Hematuria during ICI or targeted therapy may indicate treatment-related toxicity (kidney or bladder inflammation) or unrelated conditions such as infection or stones; early evaluation helps prevent complications. ^[3] Hematuria reported during pembrolizumab therapy is a recognized adverse event and merits clinical assessment. ^[5]

• Expect a structured workup: You may undergo urinalysis, kidney function tests, urine culture, and imaging; high-risk or gross hematuria typically leads to cystoscopy and cross-sectional imaging of the urinary tract. ^[15] For persistent or symptomatic hematuria, specialist urology referral is common and efficient patient pathways are recommended. ^[12]

• Management depends on cause: Infection is treated with antibiotics; stones with hydration, pain control, or procedures; immune-related nephritis or cystitis may require holding ICI and starting corticosteroids under oncology guidance; bleeding from targeted therapy may require dose adjustment or interruptions; and a detected bladder lesion will be biopsied or resected as indicated. ^{[3] [10]} Metastatic melanoma to the bladder is managed with transurethral resection and oncologic planning, though prognosis depends on overall disease status. ^[1]

---

Summary Table: Melanoma-Related Causes of Hematuria

Source	How it leads to hematuria	Key signs	Typical next steps
Bladder metastasis from melanoma	Tumor in bladder bleeds into urine	Gross hematuria, clots, possible obstruction	Cystoscopy, biopsy/resection, imaging, oncologic plan [1] [2]
Immune checkpoint inhibitors (nivolumab, pembrolizumab)	Immune-mediated kidney or bladder inflammation	Blood in urine, urinary burning, decreased urine, elevated creatinine	Stop/hold drug, labs, urinalysis, consider steroids, nephrology/urology eval [3] [5] [4]
BRAF/MEK inhibitors (dabrafenib/trametinib, trametinib)	Drug-associated bleeding events	Hematuria or bladder hemorrhage	Assess bleeding risk, monitor, possibly hold/adjust therapy, urology eval if persistent [8] [9] [10]
Other common causes (infection, stones) during cancer care	Inflammation or trauma to urinary tract	Pain, fever (infection), colicky pain (stones)	Urinalysis/culture, antibiotics or stone management, imaging as needed [17] [13]

---

Key Takeaways

• Yes melanoma itself (via bladder metastasis) and several melanoma treatments (immune checkpoint inhibitors and BRAF/MEK targeted therapies) can be associated with hematuria. ^{[1] [3] [8]}
• Visible blood in urine should be evaluated urgently, often with cystoscopy and CT urography, especially in higher-risk individuals or those with known cancer. ^{[15] [12]}
• Treatment-related hematuria requires prompt communication with your oncology team, targeted testing, and sometimes temporary treatment interruption with supportive care or steroids if immune-related toxicity is suspected. ^{[3] [5]}

If you notice blood in your urine during or after melanoma treatment, seeking timely medical assessment helps identify the cause and guide the safest next steps. ^{[12] [15]}