The Diagnosis and Treatment of Penile Cancer.

BACKGROUND: The incidence of penile cancer in Europe lies in the range of 0.9 to 2.1 cases per 100 000 persons per year. Carcinogenesis is associated with human papilloma virus (HPV) infection and with chronic inflammation. METHODS: This review is based on publications (2010-2017) retrieved by a selective search in PubMed and EMBASE and on the guidelines of the European Association of Urology, the European Society of Medical Oncology, the National Comprehensive Cancer Network, and the National Institute for Health and Care Excellence (NICE). RESULTS: 95% of cases of penile cancer are accounted for by squamous cell carcinoma, whose numerous subtypes have different clinical courses. Chronic preputial inflammation due to phimosis or lichen sclerosus is often associated with penile cancer. Circumcision lowers the risk of penile cancer (hazard ratio: 0.33). Maximally organ-preserving surgery with safety margins of no more than a few millimeters is the current therapeutic standard, because a local recurrence, if it arises, can still be treated locally with curative intent. Local radiotherapy can be performed in early stages. Lymphogenic metastasis must be treated with radical lymphadenectomy and adjuvant chemotherapy. Patients with clinically unremarkable inguinal lymph nodes nonetheless need invasive lymph node staging because of the high rate of lymphogenic micrometastasis. CONCLUSION: Penile cancer is curable in all early stages with the appropriate treatment, but its prognosis depends crucially on the proper management of the regional (i.e., inguinal) lymph nodes. In many countries, the treatment of this rare disease entity has been centralized.

Treatment Trends and Outcomes for Patients With Lymph Node-Positive Cancer of the Penis.

Importance: Penile cancer is an uncommon disease with minimal level I evidence to guide therapy. The National Comprehensive Cancer Network (NCCN) guidelines advocate a lymph node dissection (LND) or radiotherapy with consideration of perioperative chemotherapy for all patients with lymph node-positive (LN+) penile cancer without metastasis. Objectives: To determine temporal trends in use of chemotherapy for patients with LN+ penile cancer without metastasis and to evaluate outcomes between those who did or did not receive LND, chemotherapy, and radiotherapy. Design, Setting, and Participants: The US National Cancer Database (NCDB) was queried for all 1123 patients with LN+, squamous cell carcinoma of the penis without metastasis from January 1, 2004, through December 31, 2014. Temporal trends were assessed using Cochran-Armitage tests. Multivariable logistic models were used to examine the association between treatments, clinicopathologic variables, and receipt of chemotherapy. Kaplan-Meier analyses with log-rank tests and multivariable Cox regressions were used to analyze overall survival. Data were analyzed between January 2017 and September 2017. Main Outcomes and Measures: Use of chemotherapy over time. Survival outcomes by receipt or nonreceipt of LND, radiotherapy, and chemotherapy. Results: Of 1123 patients identified, most were white (924 [82.3%]) vs African American (141 [12.6%]) or of other or unknown race (58 [5.2%]). The age of most patients (727 [64.7%]) was between 50 and 75 years, and 750 patients (66.8%) underwent an LND. From 2004 to 2014, the use of systemic therapy significantly increased (26 of 68 patients, 38.2% vs 65 of 136, 47.8%; P < .001). However, only 177 of 335 patients with N3 disease (52.8%) received chemotherapy (N1: 106 of 338, 31.4%; N2: 178 of 450, 39.6%). Following adjustment, older patients (>76 years: OR, 0.28; 95% CI, 0.15-0.50; P < .001) were less likely to receive chemotherapy. Patients who received radiotherapy (OR, 4.38; 95% CI, 3.10-6.18; P < .001) and those patients with N2 (OR, 1.62; 95% CI, 1.16-2.27; P = .005) or N3 (OR, 2.32; 95% CI, 1.67-3.22; P < .001) cancer were more likely to receive chemotherapy. On multivariable analysis, LND (HR, 0.64; 95% CI, 0.52-0.78; P < .001) was associated with better overall survival, while neither chemotherapy (HR, 1.01; 95% CI, 0.80-1.26; P = .95) nor radiotherapy (HR, 0.85; 95% CI, 0.70-1.04; P = .11) was associated with overall survival. Conclusions and Relevance: In hospitals reporting to the NCDB, only 66.8% of patients with LN+ penile cancer received an LND. While chemotherapy use has increased since 2004, rates remain low (52.8% for patients with N3 cancer). Receipt of LND, but not chemotherapy or radiotherapy, is associated with overall survival. This may reflect the aggressive natural history of penile cancer as well as the inherent analysis limitation of a relatively small sample size. These data highlight opportunities to improve adherence to guideline-recommended care.

Identifying Psychosocial Distress and Stressors Using Distress-screening Instruments in Patients With Localized and Advanced Penile Cancer.

BACKGROUND: We examined the effects of treatment on the psychological well-being of patients with localized or advanced penile cancer using screening questionnaires to determine the consecutive need for psychosocial care. Penile cancer is a rare, but highly aggressive, malignancy. The psychological stress of patients with penile cancer arises from the cancer diagnosis per se and the corresponding consequences of treatment. In addition, cancer-specific distress results (eg, fear of metastasis, progression, relapse, death). Studies of the psychosocial stress of penile cancer patients are rare. MATERIAL AND METHODS: We undertook a prospective analysis of the data from patients with penile cancer who had undergone surgery or chemotherapy from August 2014 to October 2016 at our department. Patients were evaluated using standardized questionnaires for stress screening and the identification for the need for psychosocial care (National Comprehensive Cancer Network Distress Thermometer and Hornheider screening instrument) and by assessing the actual use of psychosocial support. RESULTS: The average stress level was 4.5. Of all the patients, 42.5% showed increased care needs at the time of the survey. Younger patients, patients undergoing chemotherapy, and patients with recurrence were significantly more integrated with the psychosocial care systems. Finally, 67% of all patients received inpatient psychosocial care. CONCLUSION: Owing to the potentially mutilating surgery, patients with penile cancer experience increased psychological stress and, consequently, have an increased need for psychosocial care. Therefore, the emotional stress of these patients should be recognized and support based on interdisciplinary collaboration offered.

Erythroplasia of Queyrat treated by laser and light modalities: a systematic review.

Erythroplasia of Queyrat (EOQ) is a squamous cell carcinoma in situ most commonly located on the glans penis or prepuce. EOQ accounts for roughly 10 % of all penile malignancies and may lead to invasive squamous cell carcinoma. Standard therapy includes local excision, partial or total penectomy, cryotherapy, and topical cytotoxic agents. Treatment of EOQ has proven to be challenging due to low response rates and recurrence. In addition, radical procedures can significantly affect sexual function and quality of life. Alternative laser treatments and photodynamic therapy (PDT) offer promising results for treating EOQ. A systemic review of the literature was performed for articles discussing laser and light therapy for EOQ. Among the patients treated with the CO2 laser, 81.4 % of cases had complete remission after one session of treatment. Patients treated with PDT presented with more variable results, where 62.5 % of those treated with methyl aminolevulinate photodynamic therapy (MAL-PDT) achieved complete remission. Aminolevulinic acid (ALA-PDT) treatment showed a similar rate of remission at 58.3 %. One study utilized the Nd:YAG laser, which resulted in a recurrence of the lesion in four of the five patients treated. Of the methods reviewed, the CO2 laser offered the most promising results with a cosmetically excellent prognosis. Further studies with larger power and longer follow-up times are needed to determine the optimal treatment regimen for this penile malignancy.

A Combination of Cisplatin and 5-Fluorouracil With a Taxane in Patients Who Underwent Lymph Node Dissection for Nodal Metastases From Squamous Cell Carcinoma of the Penis: Treatment Outcome and Survival Analyses in Neoadjuvant and Adjuvant Settings.

BACKGROUND: The role of chemotherapy in nodal metastases from penile squamous cell carcinoma is not defined. We evaluated the efficacy of a combination of T-PF (a taxane, cisplatin, and 5-fluorouracil) in neoadjuvant and adjuvant settings. PATIENTS AND METHODS: Since June of 2004, T-PF was administered to stage N2 to 3 patients. With time, neoadjuvant chemotherapy administration prevailed with respect to use in the adjuvant setting. Primary end points were progression-free (PFS) and overall (OS) survival. Secondary objectives were tolerability and activity in the neoadjuvant setting. Nonparametric tests, Kaplan-Meier, and regression analyses were performed. RESULTS: As of October of 2012, 47 consecutive N2 to 3 M0 patients had undergone neoadjuvant (n = 28) or adjuvant (n = 19) T-PF: 18 patients (38.3%) remain disease-free after a median follow-up of 22 months (interquartile range, 17-42 months). The 2-year disease-free survivals were 36.8% (95% confidence interval [CI], 15.2-58.5) versus 7.1% (95% CI, 0-16.7) after adjuvant and neoadjuvant therapy, respectively. N3 metastases were associated with a poorer PFS, and bilateral metastases and mutated p53 were associated with a poorer OS. After neoadjuvant treatment, 43% clinical responses and 14% complete pathologic remissions were recorded, but responses were not associated with survival. Neutropenia (25.5%) was the most frequent Grade ≥ 2 toxicity. CONCLUSION: The T-PF regimen is well tolerated and compares with other regimens in terms of activity and efficacy in the neoadjuvant setting, and very long survivals have been recorded after adjuvant administration. The role of perioperative treatment in these patients remains controversial. Some caution in administering preemptive treatment in patients with resectable disease is needed.

[Neoadjuvant and adjuvant chemotherapy with paclitaxel, cisplatin and 5-fluorouracil for advanced penile cancer: a case report].

54-year-old male was introduced to our hospital in January 2012 for surgical treatment and chemotherapy. The pathological examination revealed well differentiated squamous cell carcinoma of the penis. Computed tomography and magnetic resonance imaging indicated right inguinal and pelvic lymphadenopathy. We diagnosed the tumor to be unresectable radically and administered paclitaxel, cisplatin and 5-fluorouracil (TPF) as neoadjuvant chemotherapy. After 3 courses of chemotherapy, the size of lymphadenopathy had become small enough to allow curative surgical treatment. Partial penectomy and lymph node dissection were performed after neoadjuvant chemotherapy. For 12 months after this radical treatment, the patient has been healthy with no local resurrence and no distant metastatic lesion. TPF chemotherapy for unresectable nodal metastasis from squamous cell carcinoma of penis was suggested to be effective.

[Treatment of 58 cases of penile squamous cell carcinoma].

OBJECTIVE: To search for rational and effective treatments for penile squamous cell carcinoma (PSCC). METHODS: We retrospectively analyzed the clinical data of 58 cases of pathologically confirmed PSCC, focusing on the treatment methods. RESULTS: Based on Jackson Staging, 25 of the 58 cases fell into stage I, 18 stage II, 11 stage III, and 4 stage IV. Fifty-three of the patients were treated by surgery, of whom 43 underwent limited resection of the tumor or partial amputation of the penis, and the other 10 received total penis amputation plus perineal urethrostomy and clearance of lymphoglandulae iliacae and inguinal lymph nodes, with the lymphoglandulae iliacae positive in 1 case and the inguinal lymph nodes positive in all. Thirty-seven cases received neoadjuvant hormonal therapy (thermotherapy plus chemotherapy) and combined postoperative chemotherapy, 12 postoperative chemotherapy only, and 4 merely surgery. Five of the total number underwent chemotherapy and/or radiotherapy without surgery. The 2-5 years follow-up of 48 patients found recurrence in 4 cases of partial penis amputation within 2 years, 4 deaths within 2 years, 7 deaths from 2 to 5 years. The 2- and 5-year survival rates were 91.7% and 77.1%, respectively. Ten of the cases were lost in follow-up. CONCLUSION: Surgery + neoadjuvant hormonal therapy + postoperative chemotherapy and/or radiotherapy is an effective method for PSCC, but whether it can reduce the recurrence of PSCC and improve the survival of the patients remains to be further studied.

[Diagnosis and treatment of penis cancer]. / Diagnostic et traitement du cancer du pénis.

Penile cancer is a rare tumor in Europe and is therefore associated with risks of diagnostic delay for stage Ta-T1 tumors or pre-epitheliomatous lesions and of an inadequate treatment strategy. Clinical examination by palpation is essential in primary tumors to look for infiltration in the corpus spongiosum and the tunica albuginea of the corpus cavernosa of the penis, and in the lymphatic drainage areas, in particular in the upper inner quadrant of the inguinal lymph nodes. The work-up must include: a biopsy in the case of diagnostic doubt, lymph node aspiration in the case of palpable adenopathies, and whole-body computed tomography (CT). Treatment of the primary tumor can include partial amputation for tumors infiltrating the corpus cavernosa, or conservative treatment for tumors limited to the glands if the diameter is less than 30 mm, after an initial circumcision. Groups at risk of lymph node metastases have been defined as a function of the pathology results of their primary tumors. In these groups at risk, or in the case of clinical lymph node metastasis, dissection of the lymph node has an important role, permitting 5-year survival rates greater than 80 % when the number of metastatic lymph nodes is ≤ 1-2. In the case of more extensive lymph node spread, a combination of chemotherapy and surgery must be discussed in multidisciplinary meetings, especially for younger patients.

A case of local advanced penile cancer treated with multimodality therapy.

A 61-year-old man presented to our institution complaining of a putrescent left inguinal ulcerated tumor. Our diagnosis was penile cancer with bilateral inguinal lymph node metastasis and clinical staging T4N3M0. Here we report a case of local advanced penile cancer experimentally treated with a multimodal approach.

Photodynamic therapy following carbon dioxide laser enhances efficacy in the treatment of extramammary Paget's disease.

Surgical resection is the first-choice therapy for extramammary Paget's disease, but extensive resection is highly invasive and non-surgical treatments are sometimes preferred. Although photodynamic therapy (PDT) has been used for extramammary Paget's disease for some time, recurrence and residual tumour cells are common. In the present study, five patients with extramammary Paget's disease with a total of eight lesions first underwent carbon dioxide (CO2) laser abrasion, followed by 3 h of occlusive application of aminolaevulinic acid (ALA) and then 100 J/cm2 irradiation with a 630-nm excimer dye laser. This combination treatment regime was repeated every 2 weeks for a total of 3 times. Group 1 comprised two patients (five lesions) who received CO2 laser and ALA-PDT only. Group 2 comprised three patients (three lesions) who received CO2 laser and ALA-PDT for residual tumour cells following surgery. Follow-up examinations showed that seven lesions in five patients had not recurred after 12 months, suggesting the efficacy of the present method.

Malignant transformation of donovanosis (granuloma inguinale) in a HIV-positive patient.

Donovanosis is endemic in various parts of the world. Although donovanosis has been reported to co-exist with the human immunodeficiency virus (HIV) infection, to our knowledge there have been no reports of co-existent squamous cell carcinoma (SCC) in an HIV positive patient. In our case the patient did not respond to treatment for donovanosis and on biopsy we realized that the patient had coexistent SCC, which is hitherto unreported with granuloma inguinale.

High dose etretinate and interferon-alpha--a phase I study in squamous cell carcinomas and transitional cell carcinomas.

Simultaneous exposure to retinoids and interferons can result in enhanced antiproliferative and differentiating effects on malignant lesions. We studied the toxicity and the potential efficacy of an association of high dose etretinate and Interferon-alpha (IFN-alpha) in squamous cell carcinomas of the lung, head and neck, the esophagus, cervix and the penis, as well as in transitional carcinomas of the bladder. The treatment consisted of etretinate (Tigason) 4 mg/kg/d on 2, 3, 4 and finally 5 consecutive days every other week and IFN-alpha (Roferon) 6 Mio IU sc. q.d. for 5 days every week. Of 24 patients enrolled, 23 were assessable for toxicity and 20 for response. With two occurrences of grade 3 cutaneous toxicity, the administration of etretinate (Tigason) 4 mg/kg/d on 5 consecutive days every other week and IFN-alpha (Roferon) 6 Mio IU sc. q.d. for 5 days every week was considered to be the MTD. Toxicity was mild otherwise, mostly at grades 1 and 2 level, causing fatigue, skin peeling and erythema, mucositis and cheilitis; 3 PR (partial response) and 8 SD (stable disease) were recorded. Of the responders, one patient had become resistant to cisplatin-based chemotherapy and the other two had at no time ever received systemic therapy. We conclude that the association of high doses of etretinate and IFN-alpha has moderate activity in squamous cell carcinomas, is well tolerated, and that IFN-alpha plays a role in the improved tolerance of the retinoid.

Multidisciplinary treatment, including laser hyperthermia, for extensive regional metastasis of a penile tumor.

BACKGROUND: There is no reliable treatment for penile tumor with lymph node metastasis. METHODS: We report on a patient with a penile tumor with extensive regional metastasis that was successfully managed with combined laser hyperthermia, radiation and chemotherapy. RESULTS: The patient has survived more than 7 years without evidence of disease. CONCLUSIONS: Multidisciplinary treatment, including laser hyperthermia, may be useful for the treatment of regional metastasis of penile tumor.

A new treatment for penile conservation in penile carcinoma: a preliminary study of combined laser hyperthermia, radiation and chemotherapy.

OBJECTIVE: To investigate the role of laser hyperthermia in penis-conserving therapy for penile carcinoma. PATIENTS, MATERIALS AND METHODS: Penile carcinoma KPK-1 cells were transplanted into nude mice to induce tumour; the effects of laser hyperthermia, the chemotherapeutic agent peplomycin, or their combination on the inhibition of KPK-1 tumour growth were assessed. In a clinical study, two patients with well-differentiated, stage T2 penile tumours with corporeal involvement were treated to conserve the penis using concurrent radiation, laser hyperthermia and peplomycin. They had no pathologically identified regional lymph node metastasis. Radiation was given for 5 days a week for 3 weeks at a total dose of 30 Gy. Nd:YAG laser hyperthermia was administered at 42-43 degrees C for 15 min twice a week for 3 weeks immediately after radiation. Peplomycin (10 mg per day) was administered intravenously over 24 h together with the laser hyperthermia. RESULTS: The combined treatment with laser hyperthermia and peplomycin completely inhibited KPK-1 tumour growth, but the treatment with either laser hyperthermia or peplomycin alone had little effect. The results were also corroborated by the histopathological findings; the necrotic area in mice treated with combined therapy was much larger than that in those treated with laser hyperthermia alone. Both patients given combined laser hyperthermia, radiation and peplomycin were treated successfully, with the penis and sexual function conserved, and both survived for > 7 years with no evidence of any local or regional recurrence. There were no major complications related to the combined treatment. CONCLUSIONS: This preliminary study showed that combined treatment with laser hyperthermia, radiation and peplomycin might be a promising therapy for conserving the penis in some patients with stage T2 penile tumours.

[Therapeutic alternatives in the treatment of class T1N0 squamous cell carcinoma of the penis: indications and limitations]. / Alternative terapeutiche nel trattamento del carcinoma spinocellulare del pene di categoria T1N0: indicazioni e limiti.

At INT of Milan between 1964 and 1990, 204 consecutive native patients suffering from penile cancer have been treated. 101 (59%) patients out of 171 with invasive cancer (23 affected with Tis were excluded) have been classified T1N0M0. 74 patients have been treated with penis conserving methods, such as circumcision, radiotherapy, laser excision and primary chemotherapy + conserving surgery. Overall local failure and/or nodal relapses occurred in 27% (20/74). Relapses are significantly related with grading but there isn't any relationship with macroscopical aspect or size of the tumor. The conservative treatment had been possible in 80% of patients. In our experience T1N0 clinical stage conservative therapy does not worsen the prognosis.

[Bowenoid papulosis. Review of 4 cases in a health center]. / Papulosis bowenoide. Revisión de cuatro casos en un centro de salud.

OBJECTIVE: To check the clinical, histological, evolutionary and therapeutic characteristics of Bowen's Disease. DESIGN: A descriptive study of a crossover type. SETTING: Primary Care and a Dermatology clinic at a Health Centre. PATIENTS: There were 4 adult males, aged between 25 and 31, with pigmented papulosis lesions on their external genitals. Two of them were HIV-positive. MEASUREMENTS AND MAIN RESULTS: Clinical records were used. The diagnosis was confirmed through histological analysis. In all cases the lesions were papulosis, multiple and affecting the external genitals. The patients were clinically controlled until the lesions disappeared. The patients' sexual partners were referred to Gynaecology clinics for examination, but no pathology was found in any of them. CONCLUSIONS: Basic knowledge of Bowen's Disease in Primary Care is important given that it is essential to reach a diagnosis as early as possible, in order to monitor the patient and his partner and so avoid any future complications arising from the pathology's presence, such as tumour processes affecting the uterine cervix. The performance of histological analyses when faced with any suspicious genital lesion must be encouraged, given that this technique is non-aggressive.

Combined modality therapy for locally advanced penile squamous cell carcinoma.

We report here a patient who presented with locally advanced Jackson Stage IV penile squamous cell carcinoma who was managed with preoperative 5-fluorouracil, mitomycin C chemotherapy, and concurrent radiation therapy. He experienced an excellent partial response which allowed more limited surgery than would otherwise be indicated. He is still alive and well 5 years after completion of his treatment without side effects, local recurrence, or distant metastatic disease.