Node-positive and metastatic penile cancer
Node-positive penile cancer is squamous cell cancer of the penis that has reached the lymph nodes of the groin or pelvis, and it is where penile cancer becomes life-threatening. Treatment combines removal of the groin nodes with chemotherapy or chemoradiotherapy before or after surgery, the InPACT trial is testing the best order, and PD-1 antibodies are being added for advanced disease.
Overview
Penile squamous cell carcinoma spreads in an orderly way from the primary to the superficial and deep inguinal nodes, then to the pelvic nodes and only later to distant sites, which is why inguinal lymphadenectomy can still cure patients with limited node disease. The 2023 EAU-ASCO guideline recommends radical inguinal lymphadenectomy for a positive sentinel node or a palpable, biopsy-proven node, with pelvic lymphadenectomy when two or more inguinal nodes are involved or a node shows extranodal extension. Survival falls steeply with the number of nodes, bilateral disease, extranodal extension and pelvic involvement, and lymphadenectomy itself carries high rates of wound breakdown and lymphoedema, which minimally invasive and robotic techniques aim to reduce.
Systemic therapy is borrowed from small trials. The TIP regimen (paclitaxel, ifosfamide and cisplatin) produced responses in half of 30 patients given it before lymphadenectomy in a phase 2 trial at MD Anderson (Journal of Clinical Oncology 2010) and became the guideline neoadjuvant regimen for bulky or fixed nodes; paclitaxel and cisplatin with or without fluorouracil are alternatives. Adjuvant chemotherapy or chemoradiotherapy is offered after lymphadenectomy for pelvic node disease or extranodal extension, but the order and value of these treatments has never been randomised, which is what the international InPACT trial (International Penile Advanced Cancer Trial) is designed to answer. For metastatic disease platinum chemotherapy gives short responses, and phase 2 trials of pembrolizumab or cemiplimab, alone or with chemotherapy (HERCULES, EPIC), have shown responses in a subset, especially HPV-positive or PD-L1-positive tumours; the TG4001 HPV 16 vaccine with avelumab is also being tested in HPV 16-positive recurrent cancers.
State of the art
- Inguinal and pelvic lymphadenectomy still cures many men with limited node disease.
- TIP chemotherapy before surgery for bulky nodes is the accepted approach, on phase 2 evidence.
- InPACT is the first randomised trial to test the order of surgery, chemotherapy and radiotherapy.
Red cards
From the labels and guidelines behind the standard of care. Your team's thresholds win.- Emergency services nowBleeding or bruising
Bleeding that will not stop, black or bloody stools, or unexplained bruising when platelets are expected to be low.
- Emergency services nowHypophysitis or adrenal crisis
Persistent headache with extreme tiredness, nausea, dizziness on standing or low blood pressure. Vomiting, severe weakness or collapse is adrenal crisis.
- Emergency services nowBlood clot (lenalidomide, pomalidomide, thalidomide)
A swollen painful calf, or sudden breathlessness with chest pain; venous and arterial thromboembolism is a boxed warning and blood-thinning prophylaxis is recommended.
- Check before combiningFood and drink: Fluorouracil (5-FU)
Capecitabine: take within 30 minutes after a meal. DPD deficiency (DPYD variants) causes severe toxicity: pre-treatment genotyping is recommended in Europe.
- Check before combiningFood and drink: Pembrolizumab
No pharmacokinetic interactions expected (antibody). See the irAE guide for toxicity management.
- Check before combiningKidneys: Cisplatin
Dose reduce or avoid for CrCl below 60 (carboplatin is the alternative).
See all on the product pages:CemiplimabCisplatinFluorouracil (5-FU)IfosfamidePaclitaxel / nab-paclitaxelPembrolizumab·Printable cards in the navigator
Anatomy and lymph node drainage
- Renal cortex (RCC)
- Renal pelvis and ureter (upper tract urothelial)
- Bladder lining (non-muscle-invasive)
- Bladder muscle wall (muscle-invasive)
- Adrenal cortex
- Adrenal medulla and sympathetic chain (neuroblastoma)
- Developing kidney (Wilms tumour)
- Nodes: renal hilar
- Nodes: para-aortic and paracaval
- Nodes: obturator and iliac (bladder)
Renal cell carcinoma comes from the kidney's filtering cortex, urothelial cancer from the lining of the collecting system and bladder, and the adrenal on top hosts cortical and medullary (neuroblastoma) tumours.
- Renal cortex (RCC)
- Renal pelvis and ureter (upper tract urothelial)
- Bladder lining (non-muscle-invasive)Distant metastatic penile squamous cell carcinoma
- Bladder muscle wall (muscle-invasive)Distant metastatic penile squamous cell carcinoma
- Adrenal cortex
- Adrenal medulla and sympathetic chain (neuroblastoma)
- Developing kidney (Wilms tumour)Multiple or bilateral inguinal node metastases (pN2; lymphadenectomy with adjuvant therapy considered)
- renal hilar
- para-aortic and paracaval
- obturator and iliac (bladder)
Same organ: Non-muscle-invasive bladder cancer, Muscle-invasive and advanced bladder cancer, Bladder & urothelial cancer, Clear cell renal cell carcinoma, Papillary renal cell carcinoma, Chromophobe renal cell carcinoma, Renal cell carcinoma, Wilms tumour (nephroblastoma), Neuroblastoma (paediatric), Low-risk neuroblastoma (INRG very low and low risk, including stage MS), Intermediate-risk neuroblastoma, High-risk neuroblastoma, Adrenocortical carcinoma, Pheochromocytoma and paraganglioma (PPGL), Urethral cancer, Penile cancer, Localised penile cancer (organ-confined, node-negative), Localised adrenocortical carcinoma (ENSAT stage I to III, resectable), Advanced and metastatic adrenocortical carcinoma (ENSAT stage IV or unresectable), Hereditary pheochromocytoma and paraganglioma (SDHx, VHL, RET, NF1, MAX and TMEM127), Metastatic pheochromocytoma and paraganglioma
Show survival figures (1)
Averages across everyone diagnosed, often years ago. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.
- A minority of patients in high-income countries but the group in which most deaths occur; groin node involvement is the strongest predictor of survival.
Cases by country
No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.
One section per setting: the options named, what each is for, the trials behind them, the recorded trade-offs and the questions to ask.
Radical inguinal lymphadenectomy; pelvic lymphadenectomy when two or more inguinal nodes are involved or extranodal extension is found.
Neoadjuvant TIP chemotherapy (paclitaxel, ifosfamide, cisplatin) followed by lymphadenectomy in responders; chemoradiotherapy as an alternative within InPACT.
Adjuvant chemotherapy or chemoradiotherapy, ideally within InPACT because the benefit is unproven.
Platinum-based chemotherapy (TIP, paclitaxel-cisplatin, or with fluorouracil); PD-1 antibodies in trials or later lines (pembrolizumab, cemiplimab).
Trials of HPV-directed vaccines with checkpoint inhibition (TG4001 with avelumab).
Subtypes & biomarkers
top- Single inguinal node metastasis without extranodal extension (pN1; lymphadenectomy alone)
- Multiple or bilateral inguinal node metastases (pN2; lymphadenectomy with adjuvant therapy considered)
- Pelvic node metastasis or extranodal extension (pN3; multimodal therapy)
- Bulky or fixed inguinal nodes (neoadjuvant TIP then surgery)
- Distant metastatic penile squamous cell carcinoma
- Number, laterality and extranodal extension of inguinal nodes
- Pelvic node involvement on CT or PET-CT
- p16 immunohistochemistry and HPV DNA (prognostic, trial stratification)
- PD-L1 expression (investigational)
- TP53 and CDKN2A alterations in HPV-independent tumours
How often this target appears
- 1948Daseler describes the anatomy of inguinal lymphadenectomy for penile cancer
- 2010MD Anderson phase 2: neoadjuvant TIP produces responses in half of men with bulky nodes
- 2017InPACT opens in the United Kingdom, United States and Canada
- 2023EAU-ASCO guideline codifies node management; HERCULES reports responses to pembrolizumab with chemotherapy
Dated changes read from the records linked to this cancer: approvals, regulatory steps, reported trials, guideline versions and milestones. Newest first; no date is inferred.
All 10 changes by month →- 2026-09-18This recordNode-positive and metastatic penile cancerFacts on this page last checked
When this page itself was last checked or edited.
- 2023GuidelineNode-positive and metastatic penile cancerGuideline EAU-ASCO Collaborative Guideline on Penile Cancer 2023: After lymphadenectomy with pelvic nodes or extranodal extension
Adjuvant chemotherapy or chemoradiotherapy, ideally within InPACT because the benefit is unproven.
- 2023GuidelineNode-positive and metastatic penile cancerGuideline EAU-ASCO Collaborative Guideline on Penile Cancer 2023: Bulky or fixed inguinal nodes
Neoadjuvant TIP chemotherapy (paclitaxel, ifosfamide, cisplatin) followed by lymphadenectomy in responders; chemoradiotherapy as an alternative within InPACT.
- 2023GuidelineNode-positive and metastatic penile cancerGuideline EAU-ASCO Collaborative Guideline on Penile Cancer 2023: HPV 16-positive recurrent disease
Trials of HPV-directed vaccines with checkpoint inhibition (TG4001 with avelumab).
- 2023GuidelineNode-positive and metastatic penile cancerGuideline EAU-ASCO Collaborative Guideline on Penile Cancer 2023: Metastatic disease
Platinum-based chemotherapy (TIP, paclitaxel-cisplatin, or with fluorouracil); PD-1 antibodies in trials or later lines (pembrolizumab, cemiplimab).
- 2023GuidelineNode-positive and metastatic penile cancerGuideline EAU-ASCO Collaborative Guideline on Penile Cancer 2023: Positive sentinel node or resectable palpable nodes
Radical inguinal lymphadenectomy; pelvic lymphadenectomy when two or more inguinal nodes are involved or extranodal extension is found.
What is in development for Node-positive and metastatic penile cancer, drawn from the whole corpus: 1 items. Drugs are grouped by the most advanced trial phase they have reached anywhere; approved treatments sit under standard of care. Technologies are the methods being tested for this cancer, trials are the studies recorded here, and ideas are proposals not yet in a trial.
Trials under way · 1
- Phase Ib/II of TG4001 and Avelumab in HPV16 Positive R/M Cancers · phase 1/2 · Transgene
Open problems and what is being done
No randomised trial has ever shown that chemotherapy improves survival in penile cancer.
Lymphadenectomy causes lymphoedema and wound complications in a large share of patients.
Distant metastatic disease is rarely controlled for long.
and how the field plans to fix it →What is being done about thisAdvanced and metastatic diseaseAvailable now- IMRT / IGRT (modern external beam)Standard of care
- Sentinel lymph node biopsyStandard of care
In trialsNothing recorded yet.
Ideas and roadmapsNothing recorded yet.
Also on OnCo: Atlas of advanced disease · Invasion and metastasis.
HPV-positive and HPV-independent tumours may need different systemic strategies but are treated alike.
Trials
topTrials recruiting now
Country and place are remembered in this browser only. A postcode is sent to OpenStreetMap's Nominatim service to find coordinates when you press the button; nothing else leaves your device.
Landmark trials
Expert centres
topExpert centres
Baltimore · cancer center | United States | 0 | 2,955 | 41,449 | #10 | ||
Milan · cancer center | Italy | none recorded | 0 | 1,246 | 21,746 | #11 | |
Seoul · hospital | South Korea | none recorded | 0 | 464 | 3,248 | #22 | |
Amsterdam · cancer center | Netherlands | none recorded | 0 | 1,451 | 25,873 | #45 | |
Shanghai · hospital | China | none recorded | 0 | 2,872 | 31,534 | - | |
Wuhan · hospital | China | none recorded | 0 | 2,478 | 31,527 | - | |
Sydney · cancer center | Australia | none recorded | 0 | 2,222 | 33,278 | - | |
Beijing · hospital | China | none recorded | 0 | 1,784 | 18,230 | - | |
Utrecht · cancer center | Netherlands | none recorded | 0 | 1,422 | 20,323 | - | |
Beijing · cancer center | China | none recorded | 0 | 1,344 | 18,195 | - | |
Guangzhou · hospital | China | none recorded | 0 | 1,245 | 12,931 | - | |
Leiden · university | Netherlands | none recorded | 0 | 1,245 | 16,125 | - | |
Tianjin · cancer center | China | none recorded | 0 | 1,219 | 11,455 | - | |
Hangzhou · cancer center | China | none recorded | 0 | 1,219 | 17,635 | - | |
Beijing · hospital | China | none recorded | 0 | 1,154 | 11,808 | - |
These are the things we can measure; they are not a ranking of quality. Each column is a field on the institution record or a count over what OnCo has linked; a centre that treats many patients with Node-positive and metastatic penile cancer but is thinly recorded here will look small.
Not known: OnCo holds no case-volume or outcome figures for centres, so none are shown. Where a national audit or registry publishes them, the centre's page links to it. Default order: Newsweek rank, then trials for this cancer, then research output.
Questions to ask
topQuestions to ask your oncologist about Node-positive and metastatic penile cancer
Newly diagnosed
- What is my exact diagnosis, stage, and grade, and which tests established them?Why: Everything else follows from an accurate stage and subtype.
- Which biomarkers have been tested on my tumour (for example Number, laterality and extranodal extension of inguinal nodes, Pelvic node involvement on CT or PET-CT, p16 immunohistochemistry and HPV DNA, PD-L1 expression, TP53 and CDKN2A alterations in HPV-independent tumours), and what were the results?Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
- Which subtype is my cancer, and does that change the recommended treatment?Why: Recognised subtypes for this cancer include Single inguinal node metastasis without extranodal extension, Multiple or bilateral inguinal node metastases, Pelvic node metastasis or extranodal extension.
- Is germline (inherited) genetic testing recommended for me or my family?Why: Inherited variants can change treatment and matter for relatives.
Positive sentinel node or resectable palpable nodes
- For my situation (positive sentinel node or resectable palpable nodes), which of the standard options do you recommend and why?Why: Guideline options include: Radical inguinal lymphadenectomy; pelvic lymphadenectomy when two or more inguinal nodes are involved or extranodal extension is found.
Bulky or fixed inguinal nodes
- For my situation (bulky or fixed inguinal nodes), which of the standard options do you recommend and why?Why: Guideline options include: Neoadjuvant TIP chemotherapy (paclitaxel, ifosfamide, cisplatin) followed by lymphadenectomy in responders; chemoradiotherapy as an alternative within InPACT.
- Am I a candidate for Paclitaxel / nab-paclitaxel, Ifosfamide, Cisplatin, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
After lymphadenectomy with pelvic nodes or extranodal extension
- For my situation (after lymphadenectomy with pelvic nodes or extranodal extension), which of the standard options do you recommend and why?Why: Guideline options include: Adjuvant chemotherapy or chemoradiotherapy, ideally within InPACT because the benefit is unproven.
- Am I a candidate for Cisplatin, Paclitaxel / nab-paclitaxel, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Metastatic disease
- For my situation (metastatic disease), which of the standard options do you recommend and why?Why: Guideline options include: Platinum-based chemotherapy (TIP, paclitaxel-cisplatin, or with fluorouracil); PD-1 antibodies in trials or later lines (pembrolizumab, cemiplimab).
- Am I a candidate for Cisplatin, Paclitaxel / nab-paclitaxel, Fluorouracil (5-FU) or related drugs, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
HPV 16-positive recurrent disease
- For my situation (hpv 16-positive recurrent disease), which of the standard options do you recommend and why?Why: Guideline options include: Trials of HPV-directed vaccines with checkpoint inhibition (TG4001 with avelumab).
- How do the results of Phase Ib/II of TG4001 and Avelumab in HPV16 Positive R/M Cancers apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Any stage
- Are there clinical trials I could join, for example of Pembrolizumab, Cemiplimab, Phase Ib/II of TG4001 and Avelumab in HPV16 Positive R/M Cancers?Why: Trials are how the next standard of care is set; asking early keeps options open.
- Would a second opinion at a high-volume centre change anything, and can you help arrange it?Why: Rare or high-stakes decisions benefit from a centre that treats many similar patients.
- What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?Why: Supportive care improves quality of life and helps patients complete treatment.
- I read that “No randomised trial has ever shown that chemotherapy improves survival in penile cancer”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
- I read that “Lymphadenectomy causes lymphoedema and wound complications in a large share of patients”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
Newly diagnosed? Read the first 60 days with Node-positive and metastatic penile cancer, then print the one-page appointment sheet with room for the answers.
Print this page for your appointment (your browser's print command). These prompts are for discussion; your clinical team knows your case.
Direct links plus the targets, companies, and technologies of this cancer's products.
technologies
6targets
1drugs
6companies
5terms
3trials
1key papers
2The standard-of-care entries on the penile cancer pages, from keeping as much of the penis as is safe to staging the groins with a sentinel node procedure, follow this guideline.
Neoadjuvant TIP followed by surgery is the standard approach to bulky node-positive penile cancer in guidelines, though its randomised test against surgery first is the InPACT trial.
Latest papers
topQuery for this cancer: (TITLE:"Node-positive and metastatic penile cancer" OR ABSTRACT:"Node-positive and metastatic penile cancer" OR TITLE:"Advanced penile squamous cell carcinoma" OR ABSTRACT:"Advanced penile squamous cell carcinoma" OR TITLE:"Inguinal node-positive penile cancer" OR ABSTRACT:"Inguinal node-positive penile cancer" OR TITLE:"Locally advanced penile cancer" OR ABSTRACT:"Locally advanced penile cancer" OR TITLE:"Metastatic penile cancer" OR ABSTRACT:"Metastatic penile cancer") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Node-positive and metastatic penile cancer, not a curated reading list.
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