There are several treatment options for penile cancer, depending on staging. They include surgery, radiation therapy, chemotherapy, and biological therapy. The most common treatment is one of five types of surgery:

- Wide local excision—the tumor and some surrounding healthy tissue are removed

- Microsurgery—surgery performed with a microscope is used to remove the tumor and as little healthy tissue as possible

- Laser surgery—laser light is used to burn or cut away cancerous cells

- Circumcision—cancerous foreskin is removed

- Amputation (penectomy)—a partial or total removal of the penis, and possibly the associated lymph nodes.

Radiation therapy is usually used adjuvantly with surgery to reduce the risk of recurrence. With earlier stages of penile cancer, a combination of topical chemotherapy and less invasive surgery may be used. More advanced stages of penile cancer usually require a combination of surgery, radiation and chemotherapy.

In addition to all the above, treatment of the underlying disease like brucellosis, is important to limit disease recurrence.

Treatment of small melanomas is often not necessary, but large tumors can cause discomfort and are usually surgically removed. Cisplatin and cryotherapy can be used to treat small tumors less than 3 centimeters, but tumors may reoccur. Cimetidine, a histamine stimulator, can cause tumors to regress in some horses, but may take up to 3 months to produce results and multiple treatments may be needed throughout the horse's life. There are few viable treatment options for horses with metastatic melanoma. However, gene therapy injections utilizing interleukin-12 and 18-encoding DNA plasmids have shown promise in slowing the progression of tumors in patients with metastatic melanoma.

Prognosis can range considerably for patients, depending where on the scale they have been staged. Generally speaking, the earlier the cancer is diagnosed, the better the prognosis. The overall 5-year survival rate for all stages of penile cancer is about 50%.

While sarcoids may spontaneously regress regardless of treatment in some instances, course and duration of disease is highly unpredictable and should be considered on a case-by-case basis taking into account cost of the treatment and severity of clinical signs. Surgical removal alone is not effective, with recurrence occurring in 50 to 64% of cases, but removal is often done in conjunction with other treatments. Topical treatment with products containing bloodroot extract (from the plant "Sanguinaria canadensis") for 7 to 10 days has been reported to be effective in removing small sarcoids, but the salve's caustic nature may cause pain and the sarcoid must be in an area where a bandage can be applied. Freezing sarcoids with liquid nitrogen (cryotherapy) is another affordable method, but may result in scarring or depigmentation. Topical application of the anti-metabolite 5-fluorouracil has also obtained favorable results, but it usually takes 30 to 90 days of repeated application before any effect can be realized. Injection of small sarcoids (usually around the eyes) with the chemotherapeutic agent cisplatin and the immunomodulator BCG have also achieved some success. In one trial, BCG was 69% effective in treating nodular and small fibroblastic sarcoids around the eye when repeatedly injected into the lesion and injection with cisplatin was 33% effective overall (mostly in horses with nodular sarcoids). However, BCG treatment carries a risk of allergic reaction in some horses and cisplatin has a tendency to leak out of sarcoids during repeated dosing. External beam radiation can also be used on small sarcoids, but is often impractical. Cisplatin electrochemotherapy (the application of an electrical field to the sarcoid after the injection of cisplatin, with the horse under general anesthesia), when used with or without prior surgery to remove the sarcoid, had a non-recurrence rate after four years of 97.9% in one retrospective study. There is a chance of sarcoid recurrence for all modalities even after apparently successful treatment. While sarcoids are not fatal, large aggressive tumors that destroy surrounding tissue can cause discomfort and loss of function and be resistant to treatment, making euthanasia justifiable in some instances. Sarcoids may be the most common skin-related reason for euthanasia.

Usually the lesion is surgically removed. Primarily, there is concern that the lesion identified in a patient could be cancerous, but there is also the risk of torsion, and possibly the development of symptoms. A stable lesion, however, could be clinically followed.

Treatment involves biopsy of the lesion to identify extent of dysplasia. Complete excision of the lesion is sometimes advised depending on the histopathology found in the biopsy. Even in these cases, recurrence of the erythroplakia is common and, thus, long-term monitoring is needed.

A urogenital neoplasm is a tumor of the urogenital system.

Types include:

- Cancer of the breast and female genital organs: (Breast cancer, Vulvar cancer, Vaginal cancer, Cervical cancer, Uterine cancer, Endometrial cancer, Ovarian cancer)

- Cancer of the male genital organs (Carcinoma of the penis, Prostate cancer, Testicular cancer)

- Cancer of the urinary organs (Renal cell carcinoma, Bladder cancer)

Variants with edema can be associated with Meigs' syndrome. They may be a part of nevoid basal cell carcinoma syndrome (Gorlin syndrome).

Many oral treatments have been studied, but results so far have been mixed. Some consider the use of nonsurgical approaches to be "controversial".

Collagenase clostridium histolyticum (marketed as Xiaflex by [Auxilium]), a drug originally approved by the FDA to treat Dupuytren's contracture, is now an FDA-approved injectable drug for treatment of Peyronie's disease. The drug is reported to work by breaking down the excess collagen in the penis that causes Peyronie's disease.

Vitamin E supplementation has been studied for decades, and some success has been reported in older trials, but those successes have not been reliably repeated in larger, newer studies. A combination of Vitamin E and colchicine has shown some promise in delaying progression of the condition.

Some newer agents targeting the basic mechanisms of inflammation have been studied in larger clinical trials. These include potassium para-aminobenzoate (Potaba), pentoxifylline (acting through TGFβ1 inhibition), and Coenzyme Q10.

The efficacy of Interferon-alpha-2b in the early stages of the disease has been reported in recent publications, but it was found to be less effective in cases where calcification of the plaque had occurred in common with many treatments.

Erythroplasia of Queyrat is a squamous-cell carcinoma of the glans penis (head of the penis) or inner prepuce (foreskin) in males, and the vulvae in females. It mainly occurs in uncircumcised males, over the age of 40. Erythroplasia of Queyrat may also occur on the anal mucosa or the oral mucosa.

Some sources state that this condition is synonymous with Bowen's disease, however generally speaking Bowen's disease refers to carcinoma in situ of any location on the skin such as the lower leg. Like Bowen's disease, erythroplasia of Queyrat is associated with human papillomavirus 16 and is a precursor for invasive squamous-cell carcinoma.

It is named for French dermatologist Louis Queyrat (1856-1933), who was head of the dermatology service of l'Hôpital Ricord, a venereal hospital in Paris, now Hôpital Cochin.

Surgery, such as the "Nesbit operation" (which is named after Reed M. Nesbit (1898–1979), an American urologist at University of Michigan), is considered a last resort and should only be performed by highly skilled urological surgeons knowledgeable in specialized corrective surgical techniques. A penile prosthesis may be appropriate in advanced cases.

Tuberculoma is commonly treated through the HRZE drug combination (Isoniazid, Rifampin, Pyrazinamide, Ethambutol) followed by maintenance therapy.

Initial treatment in adults often involves simply pulling back the foreskin and cleaning the penis.

Carcinoma ex pleomorphic adenoma, abbreviated ca ex PA, is a type of cancer typically found in the parotid gland. It arises from the benign tumour pleomorphic adenoma.

Its prognosis depends on the stage. Early tumour have essentially a benign behaviour.

The principal treatment of chordee is surgery in infancy, usually by a pediatric urologist. With chordees caused by circumcision, the preferred method of surgical treatment is a z-plasty. The preferred time for surgery is between the ages of 6 and 18 months and correction is usually successful.

The main treatment for isolated epispadias is a comprehensive surgical repair of the genito-urinary area usually during the first 7 years of life, including reconstruction of the urethra, closure of the penile shaft and mobilisation of the corpora. The most popular and successful technique is known as the modified Cantwell-Ransley approach. In recent decades however increasing success has been achieved with the complete penile disassembly technique despite its association with greater and more serious risk of damage.

Surgical methods range from the complete removal of the foreskin to more minor operations to relieve foreskin tightness:

- Dorsal slit (superincision) is a single incision along the upper length of the foreskin from the tip to the corona, exposing the glans without removing any tissue.

- Ventral slit (subincision) is an incision along the lower length of the foreskin from the tip of the frenulum to the base of the glans, removing the frenulum in the process. Often used when frenulum breve occurs alongside the phimosis.

- Preputioplasty, in which a limited dorsal slit with transverse closure is made along the constricting band of skin, can be an effective alternative to circumcision. It has the advantage of only limited pain and a short time of healing relative to circumcision, and avoids cosmetic effects.

- Circumcision is sometimes performed for phimosis, and is effective, but this was becoming less common as of 2012.

While circumcision prevents phimosis, studies of the incidence of healthy infants circumcised for each prevented case of phimosis are inconsistent.

Physiologic phimosis, common in males 10 years of age and younger, is normal, and does not require intervention. Non-retractile foreskin usually becomes retractable during the course of puberty.

If phimosis in older children or adults is not causing acute and severe problems, nonsurgical measures may be effective. Choice of treatment is often determined by whether circumcision is viewed as an option of last resort to be avoided or as the preferred course.

Paraphimosis can be avoided by bringing the foreskin back into its normal, forward, non-retracted position after retraction is no longer necessary (for instance, after cleaning the glans penis or placing a Foley catheter). Phimosis (both pathologic and normal childhood physiologic forms) is a risk factor for paraphimosis; "physiologic" phimosis resolves naturally as a child matures, but it may be advisable to treat "pathologic" phimosis via long-term stretching or elective surgical techniques (such as preputioplasty to loosen the preputial orifice or circumcision to amputate the foreskin tissue partially or completely).

The foreskin responds to the application of tension to cause expansion by creating new skin cells though the process of mitosis. The tissue expansion is permanent. Non-surgical stretching of the foreskin may be used to widen a narrow, non-retractable foreskin. Stretching may be combined with the use of a steroid cream. Beaugé recommends manual stretching for young males in preference to circumcision as a treatment for non-retractile foreskin because of the preservation of sexual sensation.

Paraphimosis can often be effectively treated by manual manipulation of the swollen foreskin tissue. This involves compressing the glans and moving the foreskin back to its normal position, perhaps with the aid of a lubricant, cold compression, and local anesthesia as necessary. If this fails, the tight edematous band of tissue can be relieved surgically with a dorsal slit or circumcision. An alternative method, the Dundee technique, entails placing multiple punctures in the swollen foreskin with a fine needle, and then expressing the edema fluid by manual pressure. According to Ghory and Sharma, treatment by circumcision may be elected as "a last resort, to be performed by a urologist". Other experts recommend delaying elective circumcision until after paraphimosis has been resolved.

The type of injury dictates the treatment; however, surgery is a common treatment. Catheterization is usually a part of treatment for penis injuries; when the urethra is intact, urethral catheterization may be used, but if it has been injured, suprapubic catheterization is used. Some injuries, including animal bites, are also treated with antibiotics, irrigation, and rabies prophylaxis.

Two small randomized controlled trials (RCTs) and one larger RCT (86 subjects) tested glutamine in the prevention of platinum treatment-induced neuropathy and showed promise. As of September 2013 a larger, placebo-controlled trial is running.

A 2013 systematic review of the use of acetyl-L-carnitine, glutamine, vitamin E, glutathione, vitamin B6, omega-3 fatty acids, magnesium, calcium, alpha lipoic acid and n-acetyl cysteine as anti-CIPN adjuvants concluded that "currently no agent has shown solid beneficial evidence to be recommended for the treatment or prophylaxis of CIPN."

The condition may be treated with surgery. There are several different techniques to treat this condition. Threading a suture through the lower membrane, and then tying a tight knot around the frenulum itself is a procedure that minimises invasive action. After a few days the frenulum will weaken and eventually break apart to allow the prepuce to fully retract. Other procedures involve the cutting of the skin and require the use of sutures to help in the healing process. Stretching exercises and steroid creams may also be helpful. Alternatively, it may be treated by a reparative plastic surgery operation called a frenuloplasty, or by complete circumcision including resection of the frenulum (frenectomy).

The signs and symptoms are similar to other malignant salivary gland tumours; however, it may have been preceded by an appreciable mass that was long-standing and did not appear to be growing.

Findings that suggest a malignant salivary gland tumour include rapid growth, facial weakness (due to facial nerve compression), pain, skin ulceration, fixation of the mastoid tip

and parasthesias.

In a study of patients receiving oxaliplatin treatment, only 4 percent of those also receiving intravenous calcium and magnesium (ca/mg) before and after each oxaliplatin dose had to discontinue treatment due to neurotoxicity, compared to 33 percent who were receiving intravenous placebo; onset of neuropathy was also significantly delayed in the ca/mg patients, and only 22 percent of the ca/mg patients had long-term CIPN of grade 2 or worse compared with 41 percent of those on placebo. Overall, trials of ca/mg infusion suggest there are no serious harmful side effects and it may be an effective preventative therapy — the number of patients so far studied is small, however, and confident conclusions cannot be drawn.

The PDE5 inhibitors sildenafil (Viagra), vardenafil (Levitra) and tadalafil (Cialis) are prescription drugs which are taken orally.

A cream combining alprostadil with the permeation enhancer DDAIP has been approved in Canada as a first line treatment for erectile dysfunction.

One of the following medications maybe injected into the penis: papaverine, phentolamine, and prostaglandin E1.