Penile cancer

　　The exact cause of penile cancer is not yet clear. Currently, the theory of phimosis, phimosis, and smegma is more widely recognized. Circumcision is often related to religion, and up to 25% to 75% of patients with phimosis who have not undergone circumcision may develop penile cancer. In the Jewish community, neonates undergo circumcision, and penile cancer is extremely rare. In Islamic countries, circumcision is performed at 3 to 5 years of age, and the incidence of penile cancer is significantly lower than that of uncircumcised populations. In the United States, the incidence of penile cancer is 1 in 100,000, and the risk of developing penile cancer without circumcision is 1 in 600. Long-term stimulation of the prepuce and glans penis by bacterial products in smegma is the most important cause of penile cancer. Generally, circumcision after adulthood cannot prevent the occurrence of penile cancer because it has been stimulated by smegma for a long time. To date, no conclusive evidence has been found that smegma is a carcinogen.

　　Penile cancer may be related to viral infection. Herpes simplex virus type 2 (HSV-2) may be a carcinogen for penile cancer and cervical cancer. Relevant data show that the incidence of cervical cancer in sexual partners of penile cancer patients is 3 to 8 times higher than that of the normal group. Human papillomavirus (HPV) is a double-stranded DNA virus that can infect epithelial cells in various organs. Special types of HPV can be associated with male and female anogenital warts and cancer. In penile cancer, HPV16 accounts for 0% to 49%, HPV18 accounts for 9% to 39%, and HPV6 and HPV11 are uncommon. A group of 18 penile cancer cases in Brazil had 7 cases with HPV18 DNA sequence.

　　Oral photodynamic agent 8-methoxypsoralen (oxypentolate) and ultraviolet radiation in psoriasis patients can increase the incidence of penile cancer. Penile trauma or skin scar formation after circumcision, and the use of immunosuppressants in renal transplant patients, may be related to the occurrence of penile cancer.

　　In addition, many precancerous lesions can deteriorate into penile cancer, such as penile leukoplakia, dry penile head inflammation, penile keratosis, and viral skin diseases (condyloma acuminatum, giant condyloma acuminatum). Hyperplastic erythema (or called Kaposi's proliferative erythema) and Bowen's cell papules are the in situ cancer lesions of the penis.

　　The complications of penile cancer mainly occur during treatment and can easily cause some complications. Radiotherapy is controversial. Some advocate radiotherapy alone for penile cancer. Due to the large amount of radiation, it can cause complications such as urethral stricture, fistula, penile necrosis, and edema, which limits its application. Infection and necrosis of penile cancer can also reduce the effectiveness of radiotherapy. Early penile cancer can be treated with X-ray irradiation in combination with bleomycin, with good results.

　　Penile cancer often originates from the mucosa on the glans penis, the coronal sulcus, and the inner plate of the prepuce. For patients with phimosis, the lesions are often not discovered in the early stage.

　　1. It is more common in men aged 40 to 60 with phimosis or long prepuce.

　　2. Early cancer changes are the thickening of the epithelium of the glans penis or prepuce. Most patients present with papules, ulcers, warts, or cauliflower-like plaques on the glans penis. Subsequently, they will erode, with hard and irregular edges, and cause tingling or burning pain. There may be purulent, foul-smelling secretions. When phimosis or prepuce cannot be retracted, one can carefully feel through the prepuce for masses or nodules, and there may be tenderness locally. Early lesions are often visible only after circumcision of the prepuce.

　　3. If the early lesions are not properly treated, the condition will gradually worsen. The warty nodules will increase in size or the ulcers will expand and deepen, resulting in the prepuce becoming tense, thin, and shiny. The edges of the tumor or ulcer may protrude beyond the prepuce orifice, and then the tumor mass will break through the prepuce, resulting in cauliflower-like masses or cancerous ulcers with恶臭smelly secretions. In the late stage, the tumor continues to develop and may invade the entire penis and urethral corpus cavernosum, even infiltrating the scrotum, the contents of the scrotum, and the prepubic area tissue. The distal part of the penis may necrose, shed, and cause severe local pain due to poor blood supply. After infiltrating the urethral corpus cavernosum, urinary pain, dysuria, even urinary retention or fistula may occur.

　　4. Swelling of the inguinal lymph nodes may be due to the invasion of the tumor mass, or it may be due to inflammatory reaction. Generally, patients seeking medical attention have inguinal lymph node swelling, but most of them are due to local infection associated with penile cancer, and only a few are due to tumor metastasis.

　　When there is distant metastasis, the corresponding symptoms of the metastatic site may appear, as well as systemic emaciation, anemia, loss of appetite, and other symptoms.

　　Penile cancer currently has no ideal treatment method. An important reason is that it is often not discovered early. When obvious symptoms appear, the disease is already in the late stage. If it can be discovered early, the cure rate of penile cancer can be greatly improved, and some can even be completely cured. There are reports that the cure rate of early detection of cancer can reach 65%. This shows the importance of early diagnosis and treatment of penile cancer. So, how can tumors be discovered early? Since penile cancer often has no very obvious symptoms in the early or even middle stages, if patients do not pay attention to it in their daily life, it is indeed not easy to be discovered early. Therefore, to strive for early diagnosis and treatment of penile cancer, one should be vigilant when the following symptoms appear and seek medical attention in a timely manner.

　　1. HPV vaccine

　　To date, there are two HPV prevention vaccines registered by the European Medicines Evaluation Agency (EMEA) and the U.S. FDA. Studies have shown that in the female population with negative HPV detection, both vaccines have a high preventive effect on long-term HPV infection or occasional high-grade cervical lesions. Clinical trials after male vaccination with HPV vaccines have proven the safety and efficacy of the vaccine, so it has been approved for marketing in some countries. It is speculated that HPV vaccines may also prevent HPV-positive penile cancer, but the actual effect still needs to be verified by future clinical trials.

　　2. Use condoms

　　Although there is no 100% preventive effect, the use of condoms has a significant role in preventing and treating sexually transmitted diseases. A related clinical study is ongoing; in this trial, condoms were randomly provided to sexual partners, and it was found that the healing time of HPV-related genital lesions in the condom use group was significantly shortened.

　　3. Quit smoking

　　Although the specific role of smoking in the development of penile cancer is not clear, it is undoubtedly one of the risk factors for penile cancer. Smokers are much more likely to develop penile cancer than non-smokers, so actively promoting smoking cessation is one of the measures to prevent penile cancer.

　　4. Other

　　Other preventive measures include preventing phimosis, treating chronic inflammatory diseases of the reproductive organs, and improving hygiene.

　　For typical penile cancer patients, diagnosis is not difficult through clinical examination. To confirm the disease, it is necessary to take a tissue sample from the lesion site for pathological examination. Under the microscope, the most common types are keratinizing and moderately differentiated squamous cell carcinoma. There are also 7 subtypes of squamous cell carcinoma of the penis, including basaloid carcinoma, condyloma acuminatum, papillary carcinoma, sarcomatoid carcinoma, mixed carcinoma, and adenosquamous carcinoma. Other types of penile cancer are rare.

　　1. Imaging examinations

　　(1) Lymphography: It can be helpful for diagnosing metastasis, but is generally not used as a routine examination. The method of choice is the injection of contrast medium into the lymph vessels of the foot, penis, and spermatic cord; if there is metastasis, the lymph nodes can show irregularities, filling defects, lymphatic vessel deformation, compression obstruction, and other signs.

　　(2) Ultrasound: Can determine the presence of metastases in the liver and abdomen.

　　(3) CT, MRI examination: Check for metastasis in retroperitoneal and organ areas.

　　2. Other examinations

　　When the lesion is only a hard mass and has not ruptured, if it is covered by the prepuce, a prepuce circumcision should be performed to expose the lesion site. Local tissue biopsy can be used for pathological examination to confirm the diagnosis. Tissue biopsy is the most important histological diagnostic basis; the pathological type and grade of the primary tumor can be determined by histological examination of the primary tumor; biopsy of the inguinal lymph nodes can determine whether there is metastasis, which is helpful for clinical staging and the formulation of treatment plans.

　　Health knowledge intervention for penile cancer patients not only enables them to receive treatment in a timely and proactive manner but also helps patients regain confidence and improve their quality of life.

　　1. It is advisable to eat more foods that enhance immunity and have anti-cancer effects on penile malignant tumors: such as turtle, crucian carp, shrimp, crucian carp, mulberry, lychee, walnut, and other foods.

　　2. It is recommended to consume vegetables like shepherd's purse, needlefish, chrysanthemum flower, Brassica chinensis, mung bean, adzuki bean, and other foods for infections and ulcers.

　　3. For lymphadenopathy, foods such as taros, hawthorn, lilies, water chestnuts, should be eaten.

　　4. Avoid smoking, alcohol, and spicy刺激性 foods.

　　5. Avoid moldy and pickled foods.

　　6. Avoid fried, greasy, smoked, and grilled foods.

　　7. Avoid warm foods such as lamb, dog meat, chives, and other warm foods.

　　8. Anticancer and anti-adhesion foods such as walnuts, loofah, fermented soybean paste, olives, almonds, luffa, crucian carp, should be included in the diet of tumors.

　　9. To enhance the immune effect, edible turtles, tortoises, shrimps, sandworms, crucian carp, and mullets can be used.

　　10. Symptomatic treatment can be adopted with anti-ulcer foods such as shepherds' purse, snails, precious vegetables, seagulls, rapeseed, taros, mung beans, adzuki beans, wheat flour, malva verticillata, loach, and hilsa fish.

　　11. For lymphadenopathy, edible taros, red berries, lilies, mulberries, snails, and sheep's stomach can be used.

　　Penile cancer should begin treatment only after pathological confirmation to avoid unnecessary pain and psychological trauma to the patient. The formulation of a treatment plan should be based on histological type, pathological grade, clinical stage, and the patient's overall condition. Once the diagnosis is confirmed, surgical treatment should be performed immediately. Radiotherapy and chemotherapy are auxiliary measures to surgery and can have a certain effect on improving the cure rate and survival rate.

　　1. Surgical treatment

　　Including surgery for the primary tumor and inguinal lymph node surgery.

　　(1)Local penile resection: As penile cancer tends to grow infiltratively, the recurrence rate after local resection is as high as 25%～45%, and it should be used with caution. It is only suitable for:

　　①Carcinoma localized to the prepuce, which can be treated with a simple prepuce circumcision;

　　②Exophytic wart-like carcinoma located at the glans, with a diameter of 0.7cm or less and not infiltrating the corpus cavernosum;

　　③Verrucous carcinoma located at the glans, with the base not exceeding the radius of the glans;

　　The excision margin should be 0.5cm away from the tumor edge, and the incision should extend deep into the corpus cavernosum. The excised specimen should undergo comprehensive pathological examination, especially the edge. If the resection is not complete, a partial penile resection should be performed. Patients who undergo local resection must be followed up regularly.

　　(2)Partial penile resection: It is the most commonly used method for treating the primary tumor of penile cancer. It is suitable for:

　　①Penile cancer at stage I-II located at the glans, prepuce, corona, and distal penile body;

　　②Penile cancer at stage III involving the penile body, with more than 3cm of residual corpus cavernosum after resection 2cm from the tumor margin;

　　If the patient is young and the residual corpus cavernosum is 2.5cm, partial penile amputation can also be performed, but most of the scrotum needs to be excised, and the scrotal skin is used for penile urethraloplasty.

　　(3)Total penile amputation with urethral perineal fistula surgery:

　　①Large tumor, involving the penile body, with the proximal normal corpus cavernosum less than 3cm from the tumor;

　　②Intrinsically infiltrative cancer with histological grade III-IV;

　　③Recurrence at the residual stump after partial penile resection;

　　④Clinical stage III-IV, with不明显 infiltration at the base of the penis;

　　⑤Urethral involvement leading to urinary obstruction, stricture, or concurrent urethral fistula;

　　⑥Cancer of the penile body is mostly highly malignant, even if the tumor is small, it is advisable to perform a total penile amputation.

　　The resection range is to cut off the foot of the corpora cavernosa of the penis adjacent to the pubic ramus, and to remove all the corpora cavernosa of the penis, the skin of the penis, and the surrounding soft tissue around the root of the penis.

　　(4) Inguinal lymph node dissection: Penile cancer first metastasizes to the inguinal lymph nodes via the lymphatic system, and the correct treatment of inguinal lymph nodes is a key factor for improving the cure rate. However, the indications for surgery, the timing of surgery, and the scope of surgery should be flexibly controlled. The inguinal lymph node dissection should be performed in stages, preferably 2-3 weeks after the resection of the primary penile cancer. During this period, the use of antibiotics can reduce or avoid wound infection. Only a few with minor local infections can undergo surgery in one stage.

　　2. Radiotherapy

　　The advantages of radiotherapy for penile cancer include maintaining the integrity of the penis and reducing patient suffering. The indications for radiotherapy are:

　　① The primary tumor is located at the tip of the penis, with a diameter

　　② The tumor is of exophytic wart type, infiltrating the superficial layer of the penile fascia;

　　③ Tumors with low histological differentiation of cancer cells are sensitive to radiotherapy;

　　④ Young patients, especially those who refuse surgical treatment;

　　⑤ For patients with inguinal lymph node metastasis, preoperative and postoperative radiotherapy can improve the cure rate;

　　⑥ Late-stage patients can alleviate symptoms and extend their lifespan.

　　The radiotherapy for penile cancer should be selected according to the size of the tumor and the degree of infiltration, using different energy conventional X-ray therapy: inguinal lymph node metastasis is treated with 60Co, usually for prophylactic irradiation; the range of penile irradiation is determined by the size of the lesion, generally exceeding the lesion by 1-2cm, and performing partial or total penile irradiation. The inguinal irradiation should include regional lymph nodes, with a dose of 60Gy (30 times within 6 weeks). The 5-year survival rate of radiotherapy: for stage I and II cases, it can reach 100%, and for stage III cases, it decreases to 31%

　　3. Chemotherapy

　　Chemotherapy is suitable for cases in the late stage that cannot be operated on, as well as in combination with surgery and radiotherapy. Anticancer drugs commonly used in the past include fluorouracil and cyclophosphamide, but their effects are not good. Currently, it is considered that the combined application of methotrexate, vincristine, and bleomycin is more effective, and some people use cisplatin for treatment.

　　For patients with penile cancer without bilateral inguinal lymph node metastasis, after surgical treatment, the cure rate is 90%, and for those with lymph node metastasis, the 5-year survival rate is 19-38%. Additionally, young cases, early metastasis of cancer, and poor prognosis.