Penile cancer, explained from the guidelines

Penile cancer is a cancer that starts in the skin or lining tissue of the penis. More than 95 percent of penile cancers are squamous cell carcinomas, which means they begin in the flat cells that cover the surface of the glans (the head of the penis) and the inner foreskin. The guidelines, and this page, focus on squamous cell carcinoma.

It is uncommon in the United States and Europe. The EAU-ASCO guideline reports about 0.5 new cases per 100,000 men each year in the US, and the NCCN guideline notes that it makes up 0.4 to 0.6 percent of cancers in men in the US and Europe. It is much more common in parts of South America, Southeast Asia and Africa. Most men are diagnosed between the ages of 50 and 70, although younger men can be affected.

Because it is rare, there are almost no randomized trials, and many recommendations rest on retrospective studies and expert opinion. Both guidelines say so openly. There is also no American Urological Association (AUA) guideline for penile cancer, so this page is built from the joint European Association of Urology and American Society of Clinical Oncology (EAU-ASCO) guideline, which gives graded recommendations, and the National Comprehensive Cancer Network (NCCN) guideline, which describes US practice.

The outlook depends most on whether the cancer has reached the lymph nodes in the groin. The EAU-ASCO guideline cites five-year cancer-specific survival of about 95 percent when the nodes are free of cancer. That is why so much of the care plan focuses on the groin nodes, not only on the tumor on the penis.

The penis contains three long cylinders of spongy tissue. The two corpora cavernosa run along the top and fill with blood to create an erection. The corpus spongiosum runs underneath, surrounds the urethra (the tube that carries urine and semen) and widens at the tip to form the glans. In men who are not circumcised, the foreskin (prepuce) covers the glans.

Most penile cancers begin on the glans or the inner surface of the foreskin. A US review cited by NCCN found the tumor on the glans in about a third of cases and on the foreskin in about 13 percent, with the shaft less often involved. The cancer starts as a change in the surface cells, which may first be a precancerous lesion and later grow down into deeper tissue.

How deep the tumor grows is the basis of staging. A tumor that stays in the surface layer is non-invasive. One that grows into the tissue just under the surface is called T1, into the corpus spongiosum T2, and into the corpora cavernosa (the erection chambers) T3. Deeper growth raises the chance of spread and affects which operations are possible.

Penile cancer spreads in a predictable, step-by-step way: first to the lymph nodes in the groin (the inguinal nodes) on one or both sides, then to the nodes inside the pelvis, and only later to distant organs. Fewer than 5 percent of men have distant spread at diagnosis. This orderly pattern is why finding and treating groin node spread early can be curative.

The human papillomavirus (HPV), a very common sexually transmitted virus, is the main known risk factor. The NCCN guideline estimates that 45 to 80 percent of penile cancers are related to HPV, and a large review cited by EAU-ASCO found HPV in about half. HPV type 16 is the type found most often. HPV-related penile cancers may actually have a somewhat better outlook than cancers not linked to HPV. The EAU-ASCO guideline recommends that every pathology report include a p16 stain, a lab test that shows whether HPV is active in the tumor.

A tight foreskin that cannot be pulled back (phimosis) is strongly linked to invasive penile cancer, most likely because of long-term infection and inflammation trapped underneath. Other recognized risk factors are chronic inflammation of the glans (balanitis), lichen sclerosus (a scarring skin condition of the foreskin and glans; NCCN cites a 2 to 9 percent risk of later penile cancer), smoking (NCCN reports smokers are 3 to 4.5 times more likely to develop it), penile injury, poor hygiene, a history of sexually transmitted infections including HIV, and a light treatment for psoriasis called PUVA. Lower income and education are also associated, likely through access to care.

Circumcision in infancy is associated with a lower rate of invasive penile cancer, mostly by preventing phimosis. Circumcision as an adult does not seem to give the same protection, and infant circumcision does not appear to lower the risk of the precancer PeIN. HPV vaccination prevents HPV infection, and because up to half of invasive penile cancers and most precancers are HPV-related, the EAU-ASCO guideline encourages it, while noting there is not yet good evidence measuring its effect on invasive penile cancer itself.

Practical steps that lower risk include not smoking, good genital hygiene, HPV vaccination at the recommended ages, and seeing a doctor early for a foreskin that has become tight or a sore that is not healing.

Penile intraepithelial neoplasia, or PeIN, means abnormal cells are confined to the surface layer of the skin and have not invaded deeper. It is staged as Tis (carcinoma in situ). Older names you may still hear include erythroplasia of Queyrat, Bowen's disease and bowenoid papulosis. PeIN often looks like a red, velvety or white patch on the glans or foreskin and can be mistaken for a rash or a fungal infection.

PeIN matters because it can turn into invasive cancer. The EAU-ASCO guideline reports that 2.6 to 13 percent of PeIN lesions progress to invasive cancer even with treatment, so the goal is complete removal followed by careful monitoring. Up to 80 percent of these precancers are HPV-related.

A biopsy is needed to confirm PeIN before any non-surgical treatment, such as a cream or laser, because a surface treatment could miss a deeper invasive area.

Most penile cancers appear as a visible or palpable change on the penis. NCCN describes lesions that may be nodular (a lump), ulcerated (an open sore) or fungating (growing outward like a cauliflower), as well as flat patches. The lesion may be hidden under a tight foreskin and noticed only because of bleeding, discharge or a bad smell from under the foreskin.

Pain is not always present early. With more advanced disease, men may notice lumps in the groin, or general symptoms such as tiredness and weight loss. Swollen groin nodes can also be caused by infection of the tumor rather than cancer, so they need proper testing. The EAU-ASCO guideline advises against giving a course of antibiotics to see whether the nodes shrink, because that delays staging and treatment.

Delay is a real problem in this cancer. Embarrassment, fear, or being told a sore is a fungal infection can mean months pass before a biopsy, and the EAU-ASCO guideline lists missed or incorrect diagnosis among the unmet needs of men with penile cancer. Any penile sore, lump or patch that has not healed within a few weeks deserves an examination, and a biopsy if there is any doubt.

The first step is a careful examination of the whole penis and both groins. The doctor records the size, location and appearance of the lesion, whether it seems to involve deeper structures, and the number and features of any groin nodes that can be felt. For estimating tumor size and depth, this examination is often as reliable as a scan.

A biopsy confirms the diagnosis and shows the grade and other features that predict spread to the lymph nodes. It may be a small punch biopsy under local anesthetic, an incisional biopsy (removing part of the lesion) or an excisional biopsy (removing all of it, which for small tumors can be the treatment itself). The EAU-ASCO guideline notes that very small biopsies often cannot show how deep a tumor goes, so a deeper incisional biopsy is preferred when depth matters.

MRI of the penis is not needed for everyone. EAU-ASCO suggests it when it is unclear whether the tumor has reached the corpora cavernosa or whether organ-sparing surgery is possible, with ultrasound as an alternative. For men whose groins feel normal, CT, MRI and PET scans cannot find very small deposits of cancer in the nodes, so EAU-ASCO does not recommend routine body scans in this group and relies instead on surgical staging for higher-risk tumors. NCCN, by contrast, recommends CT or MRI of the chest, abdomen and pelvis for intermediate and high-risk tumors even when no node can be felt.

When a groin node can be felt, both guidelines recommend a needle biopsy (usually guided by ultrasound or CT) to confirm cancer, and imaging of the pelvis and body with CT or FDG-PET/CT to look for spread before treatment begins.

Both guidelines use the TNM system (8th edition). T describes how deep the tumor on the penis has grown, N describes the lymph nodes, and M describes spread to distant organs. Nodes are staged twice: a clinical stage (cN) based on examination and scans, and a pathological stage (pN) once nodes have been removed and examined under the microscope.

Grade describes how abnormal the cells look: grade 1 is well differentiated (closest to normal), grade 2 moderately differentiated, and grade 3 poorly differentiated. Higher grade, and cancer seen inside small blood or lymph vessels (lymphovascular invasion) or around nerves (perineural invasion), raise the chance of node spread. These features divide T1 tumors into T1a and T1b.

After surgery, pN1 means one or two cancerous nodes on one side of the groin, pN2 means three or more on one side or nodes on both sides, and pN3 means pelvic nodes or cancer breaking through the node capsule (extranodal extension).

To decide how to handle groin nodes that feel normal, the EAU-ASCO guideline groups tumors by risk. Low risk is Tis, Ta and T1a grade 1. Intermediate risk is T1a grade 2, with a 6 to 8 percent chance of hidden node spread. High risk is T1b or higher; for example, T1b grade 2 tumors carry a 22 to 30 percent chance. NCCN uses two groups: low risk (Tis, Ta, T1a) and intermediate or high risk (T1b, or T2 and above).

Treatment answers two separate questions: how to remove the tumor on the penis, and how to manage the lymph nodes in the groins. These can be handled at the same operation or in stages, and the plan for one depends on the findings of the other.

For the primary tumor, the aim is complete removal while preserving as much of the penis as possible. Organ-sparing treatment gives better appearance and function and is the preferred approach when the tumor allows it. The trade-off is a higher chance of the cancer coming back at the same spot. In lower-risk tumors, a local recurrence can usually be treated without harming survival, but in larger or higher-grade tumors a local recurrence has been linked to worse survival, so a wider operation may be the safer choice.

The choice depends on the tumor's size, stage, grade and location, your health, your preferences, and whether you can commit to strict follow-up. Because there are no randomized trials comparing the options, the EAU-ASCO guideline asks doctors to give a balanced, individualized explanation of the benefits and harms of each treatment and to reach a decision together with you.

Penile cancer is best managed by a team that sees it regularly. EAU-ASCO describes improved results after care for this cancer was centralized in the United Kingdom, and NCCN states that the best management for any patient with cancer is in a clinical trial.

When PeIN involves the foreskin, circumcision is usually the first surgical step. After circumcision, the skin of the glans thickens over 3 to 6 months, and some remaining PeIN or lichen sclerosus may settle.

Topical creams are a common first treatment. Imiquimod works by stirring up the immune system against abnormal cells, and 5-fluorouracil (5-FU) is a chemotherapy cream. NCCN lists imiquimod 5 percent applied at night three times a week for 4 to 16 weeks, and 5-FU 5 percent applied twice daily for 2 to 6 weeks. Reported response rates range from 40 to 100 percent for imiquimod and 48 to 74 percent for 5-FU. Both cause redness, raw areas and crusting, and about 12 percent of men stop early because of side effects. The area must be checked after treatment, with a biopsy if there is doubt. If a cream fails, the EAU-ASCO guideline says it should not be repeated, because a poor response may signal a hidden invasive cancer.

Laser treatment with a CO2 or Nd:YAG laser can destroy the abnormal surface. Responses are reported in 52 to 100 percent, but recurrence in 7 to 48 percent, possibly because the laser does not reach deep enough or areas are missed. Some men notice a change in sensitivity of the glans afterward.

Surgery is used for extensive PeIN, PeIN at the edges of an earlier excision, or PeIN that returns after cream or laser. Glans resurfacing removes the full surface layer of the glans and covers it with a thin skin graft. Recurrence is low and appearance is generally acceptable. Because the whole surface is examined, surgery also finds hidden invasion: in one study, up to 20 percent of men thought to have PeIN turned out to have invasive cancer.

When an invasive tumor is confined to the glans and foreskin, the EAU-ASCO guideline recommends organ-sparing surgery for men willing to attend strict follow-up. Tumors of the foreskin are treated by radical circumcision. Small tumors of the glans or the ridge behind it can be removed by wide local excision with a rim of normal-looking skin. Superficial invasive tumors can be treated with glans resurfacing plus a deeper excision at the point of invasion. Larger glans tumors are treated by partial or total glansectomy, removal of the head of the penis, with a skin graft to build a new glans.

For glansectomy, the EAU-ASCO review reports five-year recurrence-free rates of 78 to 96 percent, graft loss in 1.5 to 23.5 percent, narrowing of the urine opening (meatal stenosis) in 2.8 to 14.3 percent, and normal erections in 50 to 100 percent. There is no agreed safe margin width, but margins under 1 mm were linked to more local recurrence in one large series. A frozen section, a quick check of the edges under the microscope during the operation, may be used when the surgeon is unsure the tumor is fully removed.

Radiotherapy is another way to keep the penis. After circumcision, it can be given as brachytherapy, where radioactive sources are placed directly in the tumor, or as external beam radiation. Brachytherapy is used for tumors under 4 cm and reports local control in 70 to 90 percent. EAU-ASCO recommends radiotherapy for selected T1 and T2 tumors; NCCN lists it as category 2B. Surgery results were slightly better in the few comparisons, and recurrence after radiation can usually be treated with surgery.

Laser treatment of invasive tumors has higher recurrence rates, and EAU-ASCO suggests limiting it to T1 tumors. Mohs surgery, which removes thin layers and checks each under the microscope, has limited data; EAU-ASCO does not recommend it routinely, while NCCN lists it for select cases (category 2B). The guidelines also differ on glansectomy for small tumors: NCCN does not recommend glansectomy for T1 grade 1 to 2 tumors unless needed to get clear margins, and lists partial penectomy among the options for all T1 tumors.

When the tumor grows into the corpora cavernosa (T3), is too large for organ-sparing surgery, or when a man prefers a more definitive operation or cannot attend close follow-up, partial penectomy is recommended. The surgeon removes the end of the penis with a margin of healthy tissue and leaves a shaft that, in most men, still allows urinating standing up and often sexual activity. Reconstruction can include repositioning the urethra to the center of the stump and grafting skin to shape a new glans.

Total penectomy is reserved for tumors so large that removing them with a safe margin would leave a stump too short to urinate standing or without wetting the scrotum. The urethra is then brought out behind the scrotum (perineal urethrostomy), and urination is done sitting down. EAU-ASCO notes that total phallic reconstruction (building a new penis) may be offered after total or near-total amputation.

Wider surgery lowers the chance of the cancer returning locally. The EAU-ASCO guideline reports local recurrence of about 4 to 5 percent after partial penectomy, compared with around 10 percent after glansectomy and up to 27 percent in some series of penis-preserving treatments. These numbers have to be weighed against the effect on sexual function and quality of life.

For locally advanced tumors that cannot be removed, chemotherapy first can shrink the tumor so that surgery becomes possible in responders, and chemoradiation is an option for men who cannot have or decline surgery. If cancer returns after organ-sparing treatment, a small recurrence that has not reached the corpora cavernosa can often be treated with another organ-sparing operation; larger recurrences usually need partial or total penectomy.

The lymph nodes decide the outlook more than anything else. EAU-ASCO cites five-year cancer-specific survival of about 95, 80, 65 and 35 percent for N0, N1, N2 and N3 disease. Early treatment of hidden node spread makes a difference: in a non-randomized study, men whose nodes were treated early had 84 percent three-year survival, compared with 35 percent when node surgery was delayed until nodes became obvious.

About 20 to 25 percent of men whose groins feel normal already have microscopic cancer in the nodes, and scans cannot reliably find it. So the decision depends on the risk features of the tumor on the penis. For low-risk tumors (Tis, Ta, T1a grade 1), the chance of spread is too low to justify surgery, and both guidelines recommend surveillance with regular groin examinations. For intermediate-risk tumors (T1a grade 2), EAU-ASCO suggests discussing surveillance as an alternative to surgical staging for men who will attend strict follow-up.

For high-risk tumors (T1b and above), surgical staging of both groins is recommended. The preferred method is dynamic sentinel node biopsy (DSNB). A small amount of radioactive tracer, often with blue dye, is injected next to the tumor to show which node or nodes drain it first. Only those sentinel nodes are removed through small cuts. If they contain cancer, the remaining nodes on that side are removed (inguinal lymph node dissection). In experienced centers, DSNB finds 92 to 96 percent of node spread with complications in 6 to 14 percent; a meta-analysis reported a false-negative rate of 12 percent overall, lower in high-volume centers. A groin ultrasound, with needle sampling of any abnormal node, is done first.

If DSNB is not available and referral is not practical, or if a man prefers it after being informed, an inguinal lymph node dissection (open, modified or video-endoscopic) can be used for staging instead, at the cost of more complications. NCCN lists bilateral inguinal dissection, bilateral DSNB (when the surgeon is experienced with it) or surveillance for intermediate and high-risk tumors, and suggests preventive radiation to the groins (category 2B) for men who are not surgical candidates or decline surgery.

When a groin node can be felt and a biopsy confirms cancer, the standard treatment is a radical inguinal lymph node dissection, removing the lymph-bearing tissue of the groin. EAU-ASCO recommends open radical dissection, or a fascia-sparing version for a single node, sparing the large saphenous vein of the leg where possible. Minimally invasive (video-endoscopic or robotic) groin dissection for palpable nodes should be done only within a clinical trial. EAU-ASCO also suggests completing groin and pelvic node treatment within three months of diagnosis.

The nodes inside the pelvis are the next step in spread. The risk of pelvic node involvement is much higher when three or more groin nodes on one side contain cancer or when cancer has broken through the node capsule. EAU-ASCO suggests removing the pelvic nodes on that side in these situations. NCCN suggests considering pelvic dissection when two or more nodes on one side are involved or there is extranodal extension, and on both sides when four or more groin nodes are involved in total.

When groin nodes are bulky (4 cm or more), fixed, or on both sides, or pelvic nodes are enlarged, chemotherapy first is preferred over surgery first. Both guidelines favor a combination containing cisplatin and a taxane; NCCN's preferred regimen is TIP (paclitaxel, ifosfamide and cisplatin), usually four courses. About half of men respond, and those who respond or remain stable then have surgery to remove all remaining disease. EAU-ASCO discourages surgery first for fixed nodes because it is rarely curative alone and often causes major wound problems.

After node surgery, extra treatment may be offered when the risk of recurrence is high. EAU-ASCO suggests radiotherapy, with or without chemotherapy, for pN2 or pN3 disease, and a balanced discussion of chemotherapy for pN3 disease if it was not given before surgery. NCCN suggests adjuvant TIP for high-risk features if chemotherapy was not given first, and lists radiotherapy or chemoradiation as category 2B options. The evidence here is limited, and trials such as InPACT are testing the best sequence.

When penile cancer has spread to distant organs, treatment aims to control the cancer, relieve symptoms and extend life. Platinum-based chemotherapy is the usual first treatment. NCCN prefers TIP and lists 5-fluorouracil plus cisplatin as an alternative. Both guidelines advise against regimens containing bleomycin because of the risk of serious lung damage.

If the cancer grows despite platinum chemotherapy, there is no standard next treatment, and both guidelines recommend a clinical trial. NCCN lists pembrolizumab, an immunotherapy drug, for tumors that test as microsatellite instability-high, mismatch repair-deficient or tumor mutational burden-high, and paclitaxel or cetuximab in selected men. EAU-ASCO notes early signs of activity for immunotherapy and anti-EGFR drugs but describes the evidence as preliminary, and reports that second-line chemotherapy has generally been followed by median survival of six months or less.

Radiotherapy is an important tool for symptom control, for example for painful or ulcerated groin masses, and NCCN gives 30 Gy in 10 treatments as a typical palliative dose. Advanced penile cancer can cause pain, odor and discharge, which affect dignity and daily life. EAU-ASCO stresses that palliative care, the specialty focused on comfort and quality of life, should be available throughout the illness and involved early, not only at the end.

Every treatment for penile cancer has side effects, and the guidelines are clear that men should hear about them before deciding. EAU-ASCO notes that many men later say knowing the effects would not have changed their decision, but they wish they had understood them better beforehand. The list below summarizes what the guidelines report for each treatment.

Lymph node surgery has the highest complication rate. Contemporary series of radical groin dissection report complications in 21 to 55 percent of men, mainly wound infection, skin edge breakdown, fluid collections (seroma or lymphocele) and lymphedema, a long-lasting swelling of the legs or genitals. Sentinel node biopsy has far fewer complications. Techniques such as sparing the saphenous vein and careful drain management help reduce problems, and early referral to a lymphedema service is advised.

Most side effects can be treated. Narrowing of the urine opening can be stretched or repaired, wound problems usually heal with care, and lymphedema can be controlled with compression, skin care and exercise. Your team can also help with erection problems and changes in urination.

Follow-up matters because a recurrence found early can often still be cured. Most local and groin recurrences appear within the first two to three years: in one study of 509 men, 52.3 percent of local recurrences occurred within two years and 79.5 percent within three. Fewer than 5 percent of regional or distant recurrences appear after two years. That supports frequent visits early and less frequent visits later, for at least five years.

Visits center on examination of the penis and both groins. Ultrasound, CT or MRI of the groins may be added when examination is difficult, for example with obesity or after earlier groin surgery. After cream or laser treatment, EAU-ASCO suggests a biopsy of the glans to confirm the area is clear. After treatment of cancerous nodes, scans of the chest, abdomen and pelvis are part of follow-up.

The two guidelines differ in detail. EAU-ASCO advises visits every 3 months for the first two years in all groups and suggests regular follow-up can end after five years if a man will reliably examine himself. NCCN spaces visits to every 6 months for some groups, adds routine imaging after node-positive disease, and continues yearly visits to year 10 after organ-sparing treatment or penectomy. Your team will choose a schedule that fits your treatment and risk.

Sexual function. Penis-preserving surgery generally preserves erections, although sensation in the glans and orgasm can change; five studies cited by EAU-ASCO found that 85 to 100 percent of men could still achieve erections after penis-preserving surgery with reconstruction. After brachytherapy, 81.5 to 100 percent of men kept potency in reported series. Partial penectomy is associated with poorer sexual outcomes overall, yet in one small study most men reported normal or only slightly reduced sexual function. Erection treatments and sex therapy can help, and partners are welcome in these conversations.

Reconstruction. Many operations include reconstruction at the same time: skin grafts to create a new glans, repositioning the urethra after partial penectomy, and flaps to close larger wounds. After total or near-total penectomy, building a new penis (phalloplasty) may be offered. EAU-ASCO includes reconstructive surgeons in the recommended team.

Urination and lymphedema. Some men urinate better after surgery because the tumor was blocking the flow, but spraying and needing to sit down or use a funnel are common after partial penectomy and can be distressing. After node surgery, swelling of the legs, scrotum or lower belly can develop. EAU-ASCO recommends good skin care, compression, exercise, specialized massage, raising the legs when resting, and prompt antibiotics for skin infections, ideally with referral to a lymphedema service before swelling becomes severe.

Emotional health. Penile cancer affects an intimate part of the body, and men describe shock, embarrassment, fear, loss of masculinity, worry about relationships and withdrawal from friends. Studies report significant anxiety in 31 percent and depression in 6 percent of men. EAU-ASCO strongly recommends discussing the psychological impact with every man and offering psychological support and counseling. Asking for this help is a normal part of care, not a sign of weakness.

Because penile cancer is rare, much of current care is based on small studies and on experience with similar cancers of the head and neck, anus and vulva. Clinical trials are how this improves. NCCN states that the best management for any patient with cancer is in a clinical trial, and EAU-ASCO strongly recommends offering trials to men whose cancer grows despite platinum chemotherapy. Your team can help you search ClinicalTrials.gov.

A second opinion is common and reasonable with a rare cancer, especially before an operation that changes the body permanently. EAU-ASCO notes that sentinel node biopsy is more accurate in high-volume centers and that survival improved in the United Kingdom after care was concentrated in specialist centers. Asking to have your pathology reviewed, or your case discussed at a multidisciplinary tumor board, is a normal request.

Most recurrences can be felt or seen, which means you are an important part of your own follow-up. EAU-ASCO recommends regular self-examination of the penis and groins, especially after formal follow-up ends. Contact your care team promptly, rather than waiting for your next visit, if you notice any of the following.

After surgery, also call for signs of wound problems or infection. If you feel persistently low, anxious or isolated, that is also a reason to reach out; support is part of treatment.