Penile Cancer

Penile cancer is a malignant tumor disease that occurs when the genetic sequence of healthy cells in the penile tissue, which is part of the male reproductive system, becomes disrupted and the cells multiply in an uncontrolled and abnormal manner. This condition, which is encountered more frequently with advancing age, is characterized by cells completely departing from their natural cycle of growth and death and forming an invasive structure in the area where they are located. This cellular deterioration, which initially develops silently, rapidly replaces healthy tissues over time and directly threatens the basic anatomical integrity and function of the organ. This disorder, which is relatively rare in the field of urological oncology, is a serious tissue anomaly that indicates a loss of control in cellular defense and repair mechanisms.

What Is Penile Cancer and Through What Process Does It Begin in the Body?

Every organ in the body consists of various cell types specialized to perform different functions. The overwhelming majority of malignant formations in this organ originate from epithelial cells, which form the outermost layer of the skin, serve as a protective barrier against external factors, and have a flat structure in shape. The transformation of these flat cells covering the outer surface into cancer over time through genetic mutations is the most common condition and accounts for nearly ninety-five percent of all cases. When the anatomical location where the tumor begins is examined, it is seen that certain regions are at much higher risk. While a large proportion of lesions arise directly in the glans at the tip, a significant portion is located in the foreskin, and some are situated in the groove connecting the glans and the shaft. Formations that begin in the shaft itself are quite rare.

Cellular subtypes other than the main type of the disease are encountered much less frequently in clinical practice.

Rare cellular origins are as follows:

• Basal cells
• Melanocytes
• Muscle tissue
• Connective tissue

The basal cells included in this list are located in the deeper layers of the skin, and tumors originating from them generally exhibit a slower growth rate. Formations originating from melanocyte cells, which give the skin its color, on the other hand, have a highly aggressive character and spread very rapidly through the lymphatic pathways. Masses developing from muscle or connective tissue also belong to this rare disease group. Specific lesions directly involving the tip may be encountered, particularly in individuals carrying viral infections that severely weaken the immune system, due to the collapse of immunity. In addition, not every type of cancer always originates from the tissue of that organ itself. Sometimes a disease that begins in another part of the body, for example in neighboring organs such as the prostate, bladder, or kidney, may spread here through the blood or lymphatic circulation. This is called secondary spread and generally indicates that the primary disease has reached a very advanced stage in the body.

What Are the Main Risk Factors Involved in the Development of Penile Cancer?

Rather than a genetic or hereditary predisposition, environmental factors, daily lifestyle habits, and long-term chronic infections play a much more decisive role in the development of the disease. At this point, certain viral infections are among the most notable risk factors and those most extensively studied scientifically. In particular, some types of sexually transmitted viruses enter skin cells and directly interfere with the DNA structure. These viruses disrupt the normal growth and death cycle of the cell and trigger cellular proliferation in an uncontrolled manner. When clinical data are examined, the strong presence of these viruses is detected in approximately half of individuals affected by the disease.

Another critical and completely preventable risk factor is narrowing of the foreskin and the inability to retract it. Anatomical tightness of the foreskin creates a closed area beneath the tip. In this area, a specific substance consisting of urine residues, dead skin cells, and the body’s natural secretions begins to accumulate.

The elements that accumulate in this enclosed area are as follows:

• Urine residues
• Dead cells
• Natural secretions
• Bacteria

If this area cannot be cleaned regularly, a persistent, chronic inflammatory process begins in that region over time. This continuous irritation and inflammation lasting for years disrupts the structure of healthy cells and prepares the ground for the process of cancer development. Since this closed area is completely eliminated and accumulation is prevented in individuals circumcised during childhood, the incidence of this disease in circumcised individuals is almost negligible. The use of tobacco and tobacco products is also an independent and extremely strong risk factor. Carcinogenic chemicals in cigarette smoke pass from the lungs into the bloodstream, reach the kidneys through the blood, and are excreted from the body through urine. As these toxic chemicals are expelled together with urine, they accumulate in tissues and directly damage the genetic structure of cells. Certain light therapies containing ultraviolet rays, used in the treatment of some skin diseases such as psoriasis, may also dramatically increase the risk of cancer development in skin tissue. Therefore, protecting the genital organs from ultraviolet rays with special coverings during such treatments has become one of the definitive standards of modern medicine.

Which Signs Should Be Considered as Symptoms of Penile Cancer?

At the initial stage, the disease generally manifests as very small and seemingly harmless skin changes that do not cause any pain or discomfort. The absence of pain is the greatest factor causing patients not to take the condition seriously and to postpone seeking medical attention. Many patients assume that these lesions are a simple infection, allergy, or irritation and wait for them to resolve on their own. Patients often present to urology clinics after delays lasting months with complaints of non-healing sores or gradually enlarging masses.

The symptoms that should be considered at the initial stage are as follows:

• Swelling
• Redness
• Sore
• Hardness
• Discoloration

Swelling among these symptoms generally appears as cauliflower-like or wart-like structures growing outward from the skin surface. Redness may mimic a simple fungal infection, but it does not respond to antifungal creams and remains in the same place for weeks. A sore is an open tissue defect with irregular borders that shows no tendency to heal and bleeds from time to time. Hardness is felt as areas on the skin surface that differ from normal tissue, feel firm to the touch, and have lost their elasticity. Discoloration is the loss of the tissue’s natural pink color and its transformation into a darker, brown, or purplish tone.

Other symptoms added to the condition as the disease progresses are as follows:

• Discharge
• Foul odor
• Itching
• Burning
• Urinary obstruction

Chronic, foul-smelling, and inflamed discharge coming from beneath the foreskin generally occurs as a result of the tissue beginning to die, necrosis, and becoming infected. The sensations of itching and burning arise from the tumor irritating the surrounding healthy tissues. If the disease is not treated and continues to grow deeper into the tissues, it begins to exert pressure on the urinary channel passing through the penis. In these advanced-stage conditions, the tumor mass may completely obstruct the urinary channel and cause the patient to suddenly become unable to urinate. In addition, externally noticeable painful or painless lumps may appear due to swelling of the lymph nodes in the groin region.

How Is the Diagnosis Made When Penile Cancer Is Suspected?

After listening to the patient’s complaints, the first and most important step is an extremely detailed physical evaluation. During this evaluation, the size of the lesion, its location on the tissue, its number, its relationship with the surrounding healthy structures, and its mobility are carefully examined. Not only the area where the lesion is located, but also detailed manual examination of both groin regions is one of the most vital parts of the diagnostic process. This is because the disease tends to spread first through the lymphatic system to the defense stations in the groin region.

If suspicion is strengthened as a result of the clinical evaluation, the definitive diagnosis can only be made through cellular examinations performed in a laboratory environment. For this purpose, a biopsy, which is the procedure of taking a tissue sample from the lesion, is applied.

The biopsy techniques used are as follows:

• Incisional biopsy
• Excisional biopsy
• Fine-needle biopsy

Incisional biopsy is preferred when the lesion is very large, has progressed into deeper tissues, or covers a wide area. In this technique, not the entire lesion but a small piece sufficient to understand its characteristics is surgically cut and removed. Excisional biopsy is applied when the lesion is very small, superficial, and limited to a single point. Here, the aim is to remove the entire lesion while leaving a certain amount of healthy margin around it; thus, both the diagnosis is made and the disease is completely cleared from that area. Fine-needle biopsy is generally the procedure of drawing cells with a needle under ultrasound guidance to determine whether cancer cells have spread into enlarged lymph nodes detected in the groin region.

The tissue samples taken are stained with special dyes in the pathology laboratory and examined under a microscope. After the diagnosis is confirmed, advanced radiological imaging devices are used to map the extent of the disease throughout the body.

The imaging methods used are as follows:

• Ultrasonography
• Magnetic resonance imaging
• Computed tomography
• Positron emission tomography

Magnetic resonance imaging, MRI, is particularly the most reliable tool for understanding in depth how extensively the spongy tissues inside have been invaded by cancer. Positron emission tomography, PET, which examines the entire body from head to toe, is used to screen whether there has been spread to distant organs.

How Do the Stages of Penile Cancer Determine the Course of the Disease?

Determining where the cancer is in the body, how deeply it has reached, and how far it has spread is called staging. Staging is the cornerstone of the treatment plan because the treatment of a very early-stage disease and that of a disease that has spread throughout the body are based on completely different principles. This staging system is created by taking into account the depth of the tumor at its starting point, whether it has spread to the lymph nodes, and whether it has reached distant organs.

The main stages into which the disease is classified are as follows:

• Stage 0
• Stage 1
• Stage 2
• Stage 3
• Stage 4

Stage 0 is known in medical terminology as “carcinoma in situ.” At this stage, the malignant cells are still located only in the uppermost layer of the skin as a superficial layer. The cells have not infiltrated deeper tissues and have not reached the blood vessels. At this stage, the chance of complete recovery is almost one hundred percent. In Stage 1, the cancer has begun to take root slightly in the connective tissue immediately beneath the epithelial layer. However, it has still not succeeded in entering the lymphatic channels or blood vessels. When the disease progresses to Stage 2, it begins to threaten deeper structures. The tumor may infiltrate the blood vessels or progress into the main spongy chambers that enable erection of the penis. At this stage, it is possible to clear the disease locally, but closer follow-up is required.

The structures to which the disease may spread as it progresses are as follows:

• Lymph nodes
• Bladder
• Large intestine
• Lung
• Liver
• Bones

Stage 3 is a critical threshold at which, regardless of the depth of the tumor at the initial site, cancer cells have now reached the lymph nodes in the groin region and begun to grow there. Spread to a single lymph node in the groin versus involvement of numerous lymph nodes in both groins changes the severity of the disease. Stage 4 is the most severe form of the condition. At this stage, the disease has gone beyond its original region, adhered to nearby organs such as the bladder or rectum, spread to the lymph nodes within the pelvis located much deeper than the groin region, or metastasized through the bloodstream to distant organs such as the lungs, liver, and bones. At this stage, multiple systemic treatments involving the entire body become more prominent than local treatments.

Which Surgical Methods Are Applied in the Treatment of Penile Cancer?

The most effective weapon at the center of the treatment process that enables complete recovery from the disease is surgical intervention. In today’s modern urological practice, the old radical and limb-sacrificing approaches have been replaced by an “organ-preserving” philosophy. The main aim is to safely remove the cancerous tissue from the body without leaving any residue while preserving the patient’s psychological integrity, ability to urinate while standing, and sexual life at the highest possible level. While in the past it was considered necessary to remove healthy tissue at very wide distances from the visible tumor, today, thanks to immediate microscopic examination during surgery, frozen section, only the diseased area is targeted with millimetric safety margins.

The surgical methods that may be applied are as follows:

• Circumcision
• Laser surgery
• Cryotherapy
• Glans resurfacing
• Glansectomy
• Partial penectomy
• Total penectomy

Circumcision is applied in extremely early cases in which the cancer is limited only to the foreskin and has not spread to any other tissue. The affected skin is widely removed, and the disease is completely eliminated. Laser surgery is the controlled vaporization of tissue using a powerful beam of light, while cryotherapy enables cancerous cells to be frozen and destroyed using liquid nitrogen. These two methods are preferred only for very small and very superficial spot-like formations.

In the technique called glans resurfacing, the epithelial layer on the glans is completely removed as a thin membrane, as though peeling the skin of an apple. In place of this diseased surface that has been removed, a thin skin graft taken from the patient’s leg or groin is aesthetically sutured. Glansectomy is applied when the tumor has extended more deeply into the glans; the glans is completely removed, but the shaft structure is left intact and a new form is created at its tip.

Partial penectomy becomes necessary when the disease has progressed toward the shaft. While the tumor-containing area is cut and removed with safety margins, the aim is to leave enough functional tissue to allow the patient to urinate while standing. Total penectomy is the removal of the entire organ down to its root in the most advanced stages where the disease has spread extensively. In this case, to ensure urine flow, the urinary channel is connected to the perineal region between the scrotum and the anus, enabling the patient to urinate while sitting.

Which Treatments Are Applied When Penile Cancer Spreads to the Lymph Nodes?

The actual determining factor in the course of the disease and the patient’s survival is not the mass at the primary site but whether the cells have reached the defense stations, the lymph nodes, in the groin region through the lymphatic pathways. Therefore, determining and managing the status of the lymph nodes constitutes the most delicate, technically challenging, and important stage of treatment.

Dynamic sentinel lymph node biopsy is applied when there is a risk of microscopic spread of the tumor even though no externally palpable swelling is present in the groin region. In this technique, a radioactive substance or special dye is injected around the tumor shortly before surgery. The lymphatic pathways carry this substance to the first station in the groin, the sentinel lymph node. During surgery, only this first lymph node is located and removed and immediately sent to the pathologist. If it is clear, no other lymph node is removed. However, if cancer cells are seen in this node or if the patient already has enlarged lymph nodes in the groin, “radical lymphadenectomy,” the procedure of removing all the lymph nodes in that region as a single package, becomes necessary. Today, this procedure can be performed much more safely through closed ports using robotic surgical systems instead of long incisions.

Conditions that may occur after groin surgery are as follows:

• Lymphedema
• Seroma
• Wound infection
• Skin necrosis

Lymphedema is the disruption of fluid drainage due to removal of the lymph nodes and the development of permanent, severe swelling in the legs. Seroma is the accumulation of fluid beneath the suture line in the area where the lymphatic tissues were removed. Wound infection and skin necrosis, the death of tissue due to inadequate blood supply, result from the sensitivity of the region. In modern medicine, intensive rehabilitation programs such as special physiotherapy massages, decongestive bandages, and graduated compression stockings that must be used for life are introduced to manage lymphedema and preserve the patient’s quality of life.

What Are the Additional Non-Surgical Treatment Options for Penile Cancer?

Management of the disease is not limited to a surgical intervention alone. Depending on the progression of the stage, the structure of the tumor, and the extent of spread, multimodal treatment protocols involving medical oncology and radiation oncology specialists are applied. The use of systemic or regional additional agents to eliminate cancer cells from the body significantly increases the success rate.

Additional treatments that may be used are as follows:

• Topical chemotherapy
• Systemic chemotherapy
• External radiotherapy
• Brachytherapy
• Immunotherapy

Topical chemotherapy is the application of special anticancer medications in cream form directly onto the lesion for very, very early-stage diseases located only in the uppermost layer of the skin. In this way, regional cellular destruction is achieved without the need for surgery. Systemic chemotherapy consists of powerful anticancer medications administered into the bloodstream through a vein and circulated throughout the entire body. If the tumors in the groin lymph nodes are very large and adhered to the tissues to such an extent that they cannot be surgically removed, chemotherapy is administered before surgery with the aim of shrinking the masses. It is sometimes also applied protectively after surgery to completely eliminate invisible microscopic cells that may remain in the blood or tissues.

External radiotherapy is the process of directing high-energy beams from an external device into the body to destroy the DNA of cancer cells. It is sometimes used after surgery to eliminate the remaining risks in the groin region. Brachytherapy is a different and much more targeted form of radiation treatment. Special radioactive seeds or cylindrical applicators are placed directly into the tumor or immediately on its surface, delivering a high dose of radiation only to that region without damaging the surrounding tissues. Immunotherapy, which has revolutionized oncology in recent years, consists of intelligent molecules that retrain the body’s own immune system rather than directly poisoning cancer cells. These medications remove the shields used by the cancer to hide from the immune system, enabling the body’s own defense cells to find and destroy the tumor.

How Does the Follow-up Process Progress After Penile Cancer Treatment?

The removal of cancer from the body and the discharge of the patient do not mean that the treatment process has ended. This disease carries a risk of reappearing, recurring, in the same area or in the lymphatic pathways, particularly during the first five-year period. Therefore, the implementation of a very strict, highly disciplined, and carefully planned clinical follow-up program is a vital necessity.

The tests regularly used during the follow-up process are as follows:

• Physical examination
• Ultrasonography
• Magnetic resonance imaging
• Computed tomography
• Chest X-ray
• Blood tests

While the first weeks after surgery focus on wound care, in the following months it is investigated whether the disease has returned. In particular, the groins, which are the area where the disease most commonly returns, are manually examined at regular intervals, and the lymph nodes are continuously screened with ultrasound devices for any enlargement. Magnetic resonance imaging and computed tomography scans are performed at certain intervals to check whether the disease has spread to the lungs or intra-abdominal organs. General body functions are evaluated through blood tests when necessary. In addition to medical follow-up, it is very important for the patient to receive psychological support and regain lost self-confidence. For suitable patients after treatment, reconstructive surgeries may be planned in cooperation with plastic surgery specialists, allowing the patient to continue life with a high level of quality and motivation.

Frequently Asked Questions