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Purpose: Our objective was to investigate the association between programmed death-ligand (PD-L1) immunoexpression measured as a combined positive score and clinical outcomes in penile SqCC. Materials and methods: We retrospectively reviewed all penile SqCC cases diagnosed in our institution between 2018 and 2023. PD-L1 immunohistochemistry was performed as a qualitative assay. Immunoexpression in both tumor and immune cells equal or superior to 1 was considered positive. Results: A total of 34 patients with conventional penile SqCC were included. Eleven cases were HPV-associated (32.4%). Twelve cases were PD-L1 CPS < 1 and twenty-two were PD-L1 CPS ≥ 1. Nine cases (32.4%) were PD-L1 CPS ≥ 1 and p16 positive, but this did not translate in worse clinicopathological features. Larger tumors (3.0 cm in PD-L1 CPS ≥ 1 vs 2.5 cm in PD-L1 CPS < 1; p = 0.662), vascular invasion (36.4% in PD-L1 CPS ≥ 1 vs. 25.0% in PD-L1 CPS < 1; p = 0.705) and perineural invasion (40.9% in PD-L1 CPS≥1 vs. 16.7% in PD-L1 CPS < 1; p = 0.252) were associated with PD-L1 expression. Among the high-risk features, only lymph node involvement had statistical significance, with 14 out of 22 PD-L1 CPS ≥ 1 patients (63.6%) having lymph node metastases when lymphadenectomy was performed (p = 0.031). With a median follow-up of 16 months (IQR 27.5), PD-L1 CPS ≥ 1 patients had worse overall survival (53.4 months vs 75.9 months), but no statistical significance could be inferred (p = 0.188). Conclusions: It is noteworthy the clinical significance of lymph node involvement in PD-L1 CPS ≥ 1 cases and a trend towards worse overall survival in this group of patients.

Background: Penile carcinoma is an uncommon cancer that develops in the penis tissue. The standard surgical method to manage regional lymph nodes after local excision is radical inguinal lymphadenectomy, but it has a high rate of complications. The objective of this retrospective study was to compare the long-term outcomes of endoscopic inguinal lymphadenectomy and open inguinal lymphadenectomy in patients with penile carcinoma. Methods: The study included patients diagnosed with penile carcinoma who underwent open inguinal lymphadenectomy (n = 23) or endoscopic inguinal lymphadenectomy (n = 27) at a single hospital between January 2013 and January 2021. Operation time, blood loss, drainage, hospital stay, postoperative complications, and survival rates were assessed and compared between the two groups. Results: The two groups were comparable in terms of age, tumor size and stage, inguinal lymph nodes, and follow-up. The endoscopic group had significantly lower blood loss (27.1 ± 1.5 ml vs 55.0 ± 2.7 ml, P < 0.05), shorter drainage time and hospital stay (4.7 ± 1.1 days vs 8.1 ± 2.2 days, and 13.4 ± 1.0 days vs 19 ± 2.0 days, respectively, P < 0.05), and longer operation time compared to the open group (82.2 ± 4.3 min in endoscopic group vs 53.1 ± 2.2 min in open group, P < 0.05). There were significant differences in the incidence of incisional infection, necrosis, and lymphorrhagia in both groups (4 vs 0, 4 vs 0, and 2 vs 0, respectively, P < 0.05). The inguinal lymph node harvested was comparable between the two groups. The mean follow-up time was similar for both groups (60.4 ± 7.7 m vs 59.8 ± 7.3 m), and the recurrence mortality rates were not significantly different. Conclusions: The study shows that both open and endoscopic methods work well for controlling penile carcinoma in the long term. But the endoscopic approach is better because it has fewer severe complications. So, the choice of surgery method might depend on factors like the surgeon's experience, what they like, and what resources are available. [ABSTRACT FROM AUTHOR]

Background: Research on penile cancer (PeCa) is predominantly conducted in countries with centralized treatment of PeCa-patients. In Germany and Austria (G + A), no state-regulated centralization is established, and no information is available on how PeCa-research is organized. Methods: Current research competence in PeCa was assessed by a 36-item questionnaire sent to all chairholders of urological academic centers in G + A. Based on PubMed records, all scientific PeCa-articles of 2012–2022 from G + A were identified. Current research trends were assessed by dividing the literature search into two periods (P1: 2012–2017, P2: 2018–2022). A bibliometric analysis was supplemented. Results: Response rate of the questionnaire was 75%, a median of 13 (IQR: 9–26) PeCa-patients/center was observed in 2021. Retrospective case series were conducted by 38.9% of participating clinics, while involvement in randomized-controlled trials was stated in 8.3% and in basic/fundamental research in 19.4%. 77.8% declared an interest in future multicenter projects. 205 PeCa-articles were identified [median impact factor: 2.77 (IQR: 0.90–4.37)]. Compared to P1, P2 showed a significant increase in the median annual publication count (29 (IQR: 13–17) vs. 15 (IQR: 19–29), p < 0.001), in multicenter studies (79.1% vs. 63.6%, p = 0.018), and in multinational studies (53% vs. 28.9%, p < 0.001); the proportion of basic/fundamental research articles significantly declined (16.5% vs. 28.9%, p = 0.041). Four of the top-5 institutions publishing PeCa-articles are academic centers. Bibliometric analyses revealed author networks, primary research areas in PeCa, and dominant journals for publications. Conclusions: Given the lack of centralization in G + A, this analysis highlights the need for research coordination within multicenter PeCa-projects. The decline in basic/fundamental research should be effectively addressed by the allocation of funded research projects. [ABSTRACT FROM AUTHOR]

Introduction: Inguinal lymph node dissection (ILND) plays an important role for both staging and treatment purposes in patients diagnosed with penile carcinoma (PeCa). Video–endoscopic inguinal lymphadenectomy (VEIL) has been introduced to reduce complications, and in those patients elected for bilateral ILND, a simultaneous bilateral VEIL (sB-VEIL) has also been proposed. This study aimed to investigate the feasibility, safety, and preliminary oncological outcomes of sB-VEIL compared to consecutive bilateral VEIL (cB-VEIL). Material and methods: Clinical N0-2 patients diagnosed with PeCa and treated with cB-VEIL and sB-VEIL between 2015 and 2023 at our institution were included. Modified ILND was performed in cN0 patients, while cN+ patients underwent a radical approach. Intra- and postoperative complications, operative time, time of drainage maintenance, length of hospital stay and readmission within 90 days, as well as lymph node yield, were compared between the two groups. Results: Overall, 30 patients were submitted to B-VEIL. Of these, 20 and 10 patients underwent cB-VEIL and sB-VEIL, respectively. Overall, 16 (80%) and 7 (70%) patients were submitted to radical ILND due to cN1-2 disease in the cB-VEIL and sB-VEIL groups, respectively. No statistically significant difference emerged in terms of median nodal yield (13.5 vs. 14, p = 0.7) and median positive LNs (p = 0.9). sD-VEIL was associated with a shorter operative time (170 vs. 240 min, p < 0.01). No statistically significant difference emerged in terms of intraoperative estimated blood loss, length of hospital stay, time to drainage tube removal, major complications, and hospital readmission in the cB-VEIL and sB-VEIL groups, respectively (all p > 0.05). Conclusions: Simultaneous bilateral VEIL is a feasible and safe technique in patients with PeCA, showing similar oncological results and shorter operative time compared to a consecutive bilateral approach. Patients with higher preoperative comorbidity burden or anesthesiological risk are those who may benefit the most from this technique. [ABSTRACT FROM AUTHOR]

In the treatment of cancer, immune checkpoint inhibitors (ICIs) have demonstrated significantly greater effectiveness compared to conventional cytotoxic or platinum-based chemotherapies. To assess the efficacy of ICI's in penile squamous cell carcinoma (pSCC) we performed a retrospective observational study. We reviewed electronic medical records of patients with penile squamous cell carcinoma (SCC), diagnosed between January 2020 and February 2023. Nine patients were screened, of whom three were ineligible for chemotherapy and received immunotherapy, cemiplimab, in a first-line setting. Each of the three immunotherapy-treated patients achieved almost a complete response (CR) after only a few cycles of therapy. The first patient had cerebral arteritis during treatment and received a high-dose steroid treatment with resolution of the symptoms of arteritis. After tapering down the steroids dose, the patient continued cemiplimab without further toxicity. The other two patients did not have any toxic side effects of the treatment. To the best of our knowledge, this is the first real world report of near CR with cemiplimab as a first-line treatment in penile SCC. [ABSTRACT FROM AUTHOR]

Sebaceous carcinoma (SC) is a rare malignant skin neoplasm derived from the meibomian gland of adnexal epithelium, which is frequently confused with basal cell carcinoma (BCC), exhibiting sebaceous differentiation and commonly found in the head and neck regions. We report a case of penile sebaceous carcinoma, an extremely rare anatomical site for SC. A 68-year-old man presented with a 4- month history of painless, non-healing ulcerated nodules over the left side of the penile shaft. Wedge biopsy showed adenocarcinoma with signet ring differentiation. We proceeded with wide local excision (WLE) of the lesion with the inclusion of the indurated skin and 5 mm of normal margin, followed by primary closure of the scrotal defect and split skin grafting of the penile shaft by using a thigh skin donor. The final histopathological examination revealed sebaceous carcinoma with pagetoid spread. The patient achieved recurrencefree survival without any form of adjuvant therapy after 4 years of follow-up. [ABSTRACT FROM AUTHOR]

Penile squamous cell carcinoma (PSCC) is a rare disease. The treatment options for advanced penile cancer are often limited, and the prognosis remains poor. We reported a 52-year-old male recurrent and metastatic PSCC patient with high PD-L1 expression (90%) and TMB (14.4 muts/Mb). He had undergone penectomy, bilateral inguinal lymph node dissection, and excision of the abdominal wall mass. Despite cisplatin-based concurrent chemoradiotherapy and sequential chemotherapy with docetaxel plus cisplatin then being carried out, the carcinoma still progressed. The patient then obtained progression-free survival with continuous sintilimab, although he experienced the new onset of ICI-induced diabetes after 24 cycles of sintilimab and required sustained insulin treatment. He had negative type 1 diabetes-associated autoantibodies and the susceptible HLA genotype DR3-DQ2 haplotype. This is the first patient with radiation and multichemorefractory PSCC who has obtained the remarkable anti-tumor effect of partial regression exceeding 32 months during continuous sintilimab and anlotinib treatment.

Penile cancer is a rare disease in developed countries and is frequently underrecognized by clinicians leading to delays in diagnosis and treatment. Squamous cell carcinoma (SCC) is the predominant pathological entity, representing 95% of all penile cancers. The most important risk factor for penile SCC is human papillomavirus (HPV) infection, with an estimated prevalence of 50%. Other major risk factors include phimosis, chronic inflammatory dermatosis, and poor genital hygiene. Two major pathophysiologic pathways have been proposed, one linked to HPV and another to chronic inflammation. Penile SCC usually presents as an erythematous area of induration or an ulcerating lesion, although changes can be more subtle in premalignant lesions [PeIN]. Confirmation of the diagnosis by biopsy and histopathological examination should be followed by staging. For localized diseases, namely PeIN, topical immunotherapy, chemotherapy, and epithelial ablative techniques are treatment options. For localized SCC, the mainstay of treatment is complete excision. Radiotherapy can be considered an organ-sparing alternative. The role of chemotherapy in penile SCC remains under discussion. The estimated 5-year overall survival is 66%, varying from 90% for T1N0M0 tumors to < 50% for patients with positive lymph nodes. Clarification of the role of HPV in premalignant lesions and penile SCC pathology has the potential to improve prevention and treatment regimens, namely through vaccination against HPV. Given its rarity and low levels of awareness by both patients and clinicians, penile SCC represents a diagnostic challenge. Prompt diagnosis is key to effective treatment since prognosis in the early stages is excellent. [ABSTRACT FROM AUTHOR]

Background: Ewing sarcoma is a malignancy that commonly affects the skeletal system and primary extraskeletal involvement is rare. Extraskeletal Ewing sarcoma (EES) arises in soft tissue anywhere in the body. These are very rarely seen aggressive tumours. There have been only 7 reported cases of EES of penis. Case Presentation: We report a 22-year-young patient who presented to our hospital with a ulcero-proliferative growth in the shaft of penis. There were no other complaints indicating any metastasis. Incisional biopsy was suggestive of invasive malignancy. He was scheduled for a partial penectomy. Final HPE and IHC were suggestive of EES. Conclusion: EES as a subtype of Ewing sarcoma is rare and it can occur in any soft tissue site. Hence, clinicians need to differentiate this entity from other soft tissue sarcomas. Early diagnosis and timely treatment of EES are pivotal for a favourable prognosis due to its aggressive nature. [ABSTRACT FROM AUTHOR]

ObjectiveExploratory study of the effect and clinical value of carbon nanoparticle suspension injection (CNSI) as a tracer for inguinal sentinel lymph nodes in penile cancer.MethodWe selected 29 patients with penile cancer in our department from January 2019 to October 2022. According to whether the CNSI tracer was injected during the pathological biopsy of the inguinal lymph nodes, the enrolled patients were assigned to the control group, the group in which CNSI was injected 12 h before the surgery (12HBS group) and the group in which CNSI was injected 0.5 h before the surgery (0.5HBS group). Evaluating the effectiveness of CNSI as a lymphatic tracer involves analyzing the following: its safety, the statistical analysis of the detection rate (DR) of different groups, the number of lymph nodes sent for each case (NOLNSFEC), the difference of positive rate of lymphatic metastasis (PROLM), and operation time (OT).ResultsThe lymph nodes in the 12HBS group and 0.5HBS group had an obvious black staining appearance, and no adverse reactions or surgical complications were found. Most of the black-stained areas caused by CNSI injection were removed with penile excision, which did not affect the postoperative appearance. This did not affect the pathological analysis. The DR of lymph nodes in the 12HBS group was higher (p

Simple Summary: Between 2002 and 2020, 31 patients with early penile cancer were treated with high-dose-rate brachytherapy (HDR-BT) at a dose of 18 × 3 Gy twice daily. The technique of the hollow steel needles fixed by the template was used. At a median follow-up of 117.5 months, the probability of local control at 5- and 10-years was 80.7% and 68.3%, respectively, with a probability of penis sparing of 80.6% and 62.1%. Cause-specific suervival was 100%. Only one case of radionecrosis was observed. These results show HDR-BT can achieve results that are comparable to low-dose rate BT while also allowing for organ preservation. Background: Low-dose-rate brachytherapy is an effective organ-sparing treatment for patients with early-stage penile cancer. However, only limited data are available on the role of high-dose-rate brachytherapy (HDR-BT) in this clinical setting. Methods: Between 2002 and 2020, 31 patients with early penile cancer were treated at our center with interstitial HDR BT at a dose of 18 × 3 Gy twice daily. A breast brachytherapy template was used for the fixation of stainless hollow needles. Results: The median follow-up was 117.5 months (range, 5–210). Eight patients (25.8%) developed a recurrence; of these, seven were salvaged by partial amputation. Six patients died of internal comorbidities or a second cancer. The probability of local control at 5 and 10 years was 80.7% (95% CI: 63.7–97.7%) and 68.3% (95% CI: 44.0–92.6%), respectively. Cause-specific survival was 100%. Only one case of radiation-induced necrosis was observed. The probability of penile sparing at 5 and 10 years was 80.6% (95% CI: 63.45–97.7%) and 62.1% (95% CI: 34.8–89.4%), respectively. Conclusions: These results show that HDR-BT for penile cancer can achieve results comparable to LDR-BT with organ sparing. Despite the relatively large patient cohort—the second largest reported to date in this clinical setting—prospective data from larger samples are needed to confirm the role of HDR-BT in penile cancer. [ABSTRACT FROM AUTHOR]

Background: Previous studies have explored the role of PD-L1 in the survival outcomes of penile cancer patients with controversies existed. Thus, the meta-analysis was conducted to report and review the association between PD-L1 and survival in penile cancer patients. Methods: PubMed, Cochrane Library, EMBASE, and Web of Science were all searched, screened, and reviewed by June 1, 2022. Hazard ratio (HR) was used to evaluate the relationship between PD-L1 and survival outcome, and odds ratio (OR) was for tumor features. Results: Nine retrospective studies (1,003 patients) were incorporated. The prevalence of PD-L1 in patients with penile cancer was 51.4% (95% CI = 42.1%-60.8%, I² = 88.5%). Higher PD-L1 on tumor cells was related to shorter cancer-specific survival (CSS) in patients (HR = 1.578, 95% CI = 1.227-2.029, I² = 23.3%), but had no associations with overall survival (OS) (HR = 1.123, 95% CI = 0.511-2.465, I² = 0.0%). Subgroup analysis indicated that higher PD-L1 was related to shorter CSS in Caucasus (HR = 1.827, 95% CI = 1.355-2.465, I² = 0.0%) only. Furthermore, PD-L1 had associations with tumor stage (pT1 vs. pT2-4, OR = 0.480, 95% CI = 0.346-0.667, P = 0.001) and tumor grade (Well and moderate vs. Poor,OR = 0.377, 95% CI = 0.264-0.538, P < 0.001). PD-L1 positivity was also related to lymph node (LN) status (pN0/NX vs. pN1--3, OR = 0.541, 95% CI = 0.385-0.759, P = 0.001) and HPV status (Positive vs. Negative, OR = 0.510, 95% CI = 0.322-0.810, P = 0.003). A trend toward statistical significance between PD-L1 and histological types was also observed (Usual SCC vs. Others, OR = 1.754, 95% CI = 0.984-3.124, P = 0.070). Conclusions: PD-L1 over-expression was related to worse survival outcomes and several clinicopathological features of penile cancer. PD-L1 expression can be applied to select appropriate treatment strategies for penile malignancies. [ABSTRACT FROM AUTHOR]

Penile squamous cell carcinoma (PSCC) is a rare disease. The treatment options for advanced penile cancer are often limited, and the prognosis remains poor. We reported a 52-year-old male recurrent and metastatic PSCC patient with high PD-L1 expression (90%) and TMB (14.4 muts/Mb). He had undergone penectomy, bilateral inguinal lymph node dissection, and excision of the abdominal wall mass. Despite cisplatin-based concurrent chemoradiotherapy and sequential chemotherapy with docetaxel plus cisplatin then being carried out, the carcinoma still progressed. The patient then obtained progression-free survival with continuous sintilimab, although he experienced the new onset of ICI-induced diabetes after 24 cycles of sintilimab and required sustained insulin treatment. He had negative type 1 diabetes-associated autoantibodies and the susceptible HLA genotype DR3-DQ2 haplotype. This is the first patient with radiation and multichemorefractory PSCC who has obtained the remarkable anti-tumor effect of partial regression exceeding 32 months during continuous sintilimab and anlotinib treatment. [ABSTRACT FROM AUTHOR]

Abstract Background Inguinal lymphadenectomy (iLAD) is effective for penile carcinoma treatment, but usually results in many complications. This study aims to clinically evaluate the feasibility and clinical significance of a laparoscopic radical iLAD approach partly preserving great saphenous vein branches for penile carcinoma patients. Methods A total of 48 patients with penile cancer who underwent laparoscopic radical iLAD with retention of the great saphenous vein in Henan Cancer Hospital from 2012 Jan to 2020 Dec were included in this study. Sixteen penile carcinoma patients who underwent laparoscopic radical iLAD preserving parts of superficial branches of the great saphenous vein were identified as the sparing group, and the matched 32 patients who incised those branches were identified as control group. This new procedure was performed by laparoscopy, preserving parts of superficial branches of the great saphenous vein, superficial lateral and medial femoral veins. Clinicopathological features and perioperative variables were recorded. Postoperative complications, including skin flap necrosis, lymphorrhagia, and lower extremity edema were analyzed retrospectively. Results We found that the operative time of the sparing group is significantly longer than the control group (p = 0.011). There was no statistical difference in intraoperative blood loss, the lymph node number per side, average time to remove the drainage tube and postoperative hospital stay between the two groups. Compared to the control group, the sparing group showed a significantly decreased incidence of lower extremity edema (p = 0.018). The preservation of parts of superficial branches of the great saphenous vein was mainly decreased the incidence of edema below ankle (p = 0.034). Conclusions This study demonstrated that the iLAD with preserving parts of superficial branches of the great saphenous vein, with a decreased incidence of postoperative complications, is a safe and feasible approach for penile cancer.

This article discusses pathological features of tumours of the male genital tract. Carcinoma of the prostate is common and represents an increasing burden to the NHS in terms of management and treatment. We focus on recent changes to grading and discuss issues around pathological diagnosis. Tumours of the testes represent the greatest success story of cancer treatment over the past several decades. We review the pathological features of the commonest tumours focusing on prognostic features. Carcinoma of the penis is rare but appears to be increasing in incidence. It requires more awareness amongst the public and general practitioners to prevent presentation at an advanced stage. We focus on pre-invasive lesions and on the pathological staging of this disease. [ABSTRACT FROM AUTHOR]

Background: Penile squamous cell carcinoma (PSCC) is a rare malignancy. However, in developing countries the incidence rate is higher. The understanding of molecular alterations is essential for evaluating possible targets for more effective systemic therapies., Methods: We retrospectively collected clinical data of metastatic PSCC (mPSCC) patients who had received at least one prior systemic treatment from 3 Brazilian hospitals. Tumor samples were evaluated using the next-generation sequencing (NGS) Foundation One DX and immunohistochemistry (IHC). The objective was to identify and describe somatic genomic alterations known to be functional or pathogenic and their association with survival outcomes., Results: Twenty-three patients were identified, 22 and 18 patients had tumor samples analyzed by IHC and NGS, respectively. PD-L1 expression (CPS ≥ 1%) was positive in 14 patients (63.6%). Regarding the genomic alterations, 16 patients (88.9%) had some clinically relevant genomic alterations. TP53, TERT, CDKN2A, PIK3CA, NOTCH1, and CDKN2B loss were identified in 66.7%, 50%, 50%, 33.3%, 27.8%, and 22.2% of the patients, respectively. No MSI or TMB high (≥10 mutations/MB) cases were identified. NOTCH1 mutation was identified only in HPV-negative patients and it was associated with worse OS (yes: 5.5 vs no: 12.8 months, P = .049) and progression-free survival (yes: 5.5 vs no: 11.7 months, P = .032)., Conclusion: This study demonstrated that molecular alterations in mPSCC from developing countries are similar to those from developed countries. Predictive biomarkers for immunotherapy response such as TMB high or MSI were not identified. Specific gene mutations may identify patients with worse prognoses and open new avenues for therapeutic development., (© The Author(s) 2024. Published by Oxford University Press.)

The presence of lymph node metastasis is the most important prognostic factor in penile cancer (PeCa). Due to limited sensitivity of currently available imaging modalities, invasive staging approaches remain indispensable for adequate nodal staging. As an alternative to radical inguinal lymphadenectomy and with the aim to reduce morbidity, staging strategies such as modified lymphadenectomy and dynamic sentinel node biopsy (DSNB) have been introduced. Over the years, DSNB evolved into a safe and reliable staging technique when performed in high volume centers. Recent enhancements of the procedure such as Single-photon emission computed tomography/computed tomography (SPECT/CT) and the introduction of hybrid tracers have improved pre- and intraoperative sentinel node (SN) visualization. Other technologies such as superparamagnetic iron oxide nanoparticles could have a potential future role to further refine DSNB. Future efforts should be aimed at optimizing diagnostic accuracy whilst minimizing perioperative morbidity. [ABSTRACT FROM AUTHOR]

Video endoscopic inguinal lymphadenectomy (VEIL), either by the classical or robot-assisted approach, is performed to manage inguinal lymph nodes in penile carcinoma. Coronary artery bypass graft (CABG) is common in the age group affected by penile carcinoma. Saphenous vein graft harvesting (SVGH) is done for CABG and may be associated with scarred subcutaneous planes hindering VEIL. A 65-year-old male was diagnosed with T2 high-grade penile carcinoma. He had undergone CABG eight years ago. He underwent robot-assisted VEIL. The initial subcutaneous space beneath Camper’s fascia was created by finger dissection and further developed by balloon inflation. A small space was made with difficulty to insert the ports. Monopolar shears were used to make a sharp dissection to develop the subcutaneous plane, and scarring was present close to Camper’s fascia. Multiple small venules were visible and managed with bipolar diathermy. The rest of the procedure was performed as usual. The console time and estimated blood loss were higher in the SVGH limb. The drain output was higher on the SVGH side. Both sides had six negative lymph nodes. Minimal skin duskiness was noted on the ipsilateral side, which healed without any sequelae. This is the first documented report of robot-assisted VEIL, post saphenous vein harvest for CABG. It is associated with a slightly longer procedure time and more blood loss, but a satisfactory oncological outcome. This report highlights the feasibility and safety of robot-assisted VEIL in post-CABG saphenous vein harvest status.

Abstract Background The high-risk human papillomavirus (HPV) infection represents one of the main etiologic pathways of penile carcinogenesis in approximately 30–50 % of cases. Several techniques for the detection of HPV are currently available including Polymerase chain reaction-based techniques, DNA and RNA in situ hybridization (ISH), p16 immunohistochemistry (IHC). The multiplex HPV RNA ISH/p16 IHC is a novel technique for the simultaneous detection of HPV E6/E7 transcripts and p16INK4a overexpression on the same slide in a single assay. The main aim of this study was to evaluate the discrepancy of p16 IHC expression relatively to HPV RNA ISH in penile cancer tissue. Methods We collected a series of 60 PCs. HPV has been analysed through the RNA ISH, p16 IHC and the multiplex HPV RNA ISH/p16 IHC. Results The multiplex HPV RNA ISH /p16 IHC results in the series were in complete agreement with the previous results obtained through the classic p16 IHC and HPV RNA scope carried out on two different slides. The multiplex HPV RNA ISH /p16 IHC showed that HPV positivity in our series is more frequently in usual squamous cell carcinoma than in special histotypes (19 out of 60 − 15 %- versus 6 out of 60 − 10 %-), in high-grade than in moderate/low grade carcinomas (6 out of 60 − 10 %- versus 4 out of 60 − 6.7 %-). In addition, our data revealed that in 5 out of 20 cases with p16 high intensity expression is not associated with HPV RNA ISH positivity. Conclusions Our findings emphasize that the use of p16 as a surrogate of HPV positivity was unsuccessful in approximatively 8 % of cases analysed in our series. Indeed, p16 IHC showed a sensitivity of 100 % and a specificity of 71 %, with a positive predictive value (PPV) of 54 % and a negative predictive value of 100 %; when considering high intensity, p16 IHC showed a sensitivity of 100 %, a specificity of 89 %, with a PPV of 75 % and NPV of 100 %. Since HPV positivity could represent a relevant prognostic and predictive value, the correct characterization offered by this approach appears to be of paramount importance.

• Penile squamous cell (PSCC) carcinoma is a rare tumor with an aggressive behavior. • Meet-URO 23/I-RARE database is a multicentric registry on rare genitourinary tumors. • This retrospective study evaluates clinical outcomes and prognostic factors in PSCC. • Patients with an ORR to I line platinum-based chemotherapy have a better survival. • Poor ECOG PS, lymph node metastases and higher age are poor prognostic factors. This retrospective study explores clinical outcomes and prognostic factors in penile squamous cell carcinoma. We included 128 patients with localized or metastatic penile carcinoma included into the Meet-URO 23/I-RARE Italian registry. Different survival outcomes were found according to clinical factors, such as ECOG PS, median age, type of response to first-line therapy. Relevant prognostic factors were ECOG PS 2-4 at diagnosis, lymph node metastases, age >77 years, and regimens with platinum plus taxane. Penile squamous cell carcinoma (PSCC) is a rare tumor with an aggressive behavior. The Meet-URO 23/I-RARE registry includes rare genitourinary malignancies. We extracted patients with PSCC to conduct a retrospective study aimed at assessing clinical outcomes and prognostic factors. Primary endpoints were overall survival and progression-free survival. Prognostic factors for OS and PFS were analyzed using univariate and multivariate analysis. From the Meet-URO 23/I-RARE database, we extracted 128 patients with diagnosis of PSCC. About 48% of patients underwent first-line of therapy. In the overall population, median OS from diagnosis was 34.6 months. Significant differences in median OS were observed according to ECOG PS at diagnosis (57.3 months vs. 8.3 months; P <.001), and median age (≤77y 88.8 months vs. >77y 26 months; P =.013). At multivariate analysis, ECOG PS 2-4 at diagnosis (HR 3.04) and lymph node metastases (HR 2.49) were independently associated with a higher risk of death. Among patients undergoing first-line therapy (n = 61), median OS was 12.3 months, and a statistically significant difference was found according to type of response to first-line (DCR 24.4 months vs. PD 7.1 months; P <.001). Multivariate analysis showed that only age >77 years was associated with a worse OS (HR 2.16). A statistically significant difference in PFS was found according to platinum plus 5-fluorouracil versus platinum plus taxane (4.9 vs. 3.4 months; P =.036) and regimens with 2 versus 3 drugs (3.4 vs. 8.6 months; P =.019). At the multivariate analysis only regimens with platinum plus taxane were associated with worse PFS (HR 2.83). In our registry study, PSCC is confirmed to be an aggressive disease. Poor ECOG PS, presence of lymph node metastases, and higher age at diagnosis appear to be associated with worse survival outcomes. [ABSTRACT FROM AUTHOR]

Background: Inguinal lymphadenectomy (iLAD) is effective for penile carcinoma treatment, but usually results in many complications. This study aims to clinically evaluate the feasibility and clinical significance of a laparoscopic radical iLAD approach partly preserving great saphenous vein branches for penile carcinoma patients.Methods: A total of 48 patients with penile cancer who underwent laparoscopic radical iLAD with retention of the great saphenous vein in Henan Cancer Hospital from 2012 Jan to 2020 Dec were included in this study. Sixteen penile carcinoma patients who underwent laparoscopic radical iLAD preserving parts of superficial branches of the great saphenous vein were identified as the sparing group, and the matched 32 patients who incised those branches were identified as control group. This new procedure was performed by laparoscopy, preserving parts of superficial branches of the great saphenous vein, superficial lateral and medial femoral veins. Clinicopathological features and perioperative variables were recorded. Postoperative complications, including skin flap necrosis, lymphorrhagia, and lower extremity edema were analyzed retrospectively.Results: We found that the operative time of the sparing group is significantly longer than the control group (p = 0.011). There was no statistical difference in intraoperative blood loss, the lymph node number per side, average time to remove the drainage tube and postoperative hospital stay between the two groups. Compared to the control group, the sparing group showed a significantly decreased incidence of lower extremity edema (p = 0.018). The preservation of parts of superficial branches of the great saphenous vein was mainly decreased the incidence of edema below ankle (p = 0.034).Conclusions: This study demonstrated that the iLAD with preserving parts of superficial branches of the great saphenous vein, with a decreased incidence of postoperative complications, is a safe and feasible approach for penile cancer. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) infection is one of the most common sexually transmitted infections. HPV high risk (HPVHR) were HPV16,18 related with invasive penile carcinomas, and HPV low risk (HPVLR) were HPV6,11 related to anogenital warts. Male infection is usually asymptomatic that it would be explain increasing the incidence of HPV associated cancers. Identification HPV genotype is very important for predicting the development of the diseases, to be benign or malignant cancer. The objective of this study was to identify the genotype of HPV that infect men with anogential warts. This research used 12 biopsy specimens from men patient with anogenital warts at Outpatient clinic of Department Dermatology and Venereology, Dr. Soetomo General Hospital period 2016-2017. The specimens were diagnozed by pathologist and HPV gentoyping was done to detect 40 HPV genotype including HPVHR and HPVLR. The result showed that 58% (7/12) were positive for HPVLR and 42% (5/12) were positive for HPV LR/HR. The genotype HPV that infected men patient with anogenital warts is HPVLR (HPV6,11) and HPVHR (HPV18,51,52,82) with single infection of HPVLR or mutiple infection HPVLR/LR or HPVLR/HR. The infection of HPVHR would be develops to be malignant transformation. It suggested that HPV genotype needs to be checked the for the anogenital warts cases for predicting the development of the diseases.

Abstract Background Approximately 50% of cases of penile carcinoma (PeCa), a rare neoplasm worldwide, are associated with human papillomavirus (HPV). However, the detection of HPV-DNA is not sufficient to consider it the etiological factor in the development of this type of cancer. Currently, the overexpression of P16INK4A is used as a surrogate biomarker of HPV carcinogenesis. Information on PeCa in Mexico is scarce, particularly regarding cases related to HPV and genotype frequency. Objective To evaluate the presence of HPV, its genotypes, and the presence of multiple genotypes, and the expression of P16INK4A, as well as its clinical and histopathological parameters. Methods For HPV-DNA detection and P16INK4A expression, we used the INNO-LiPA® test and immunohistochemistry, respectively. Results Sixty cases of PeCa were evaluated, of which 75% were HPV-non-related histological variants. We found that 58.9% (33/56) of PeCa cases were HPV-DNA positive, while 30.9% of the cases evaluated (17/55) were positive for P16INK4A. HPV16 was the main genotype in 42.9% of the cases, followed by HPV52 in 7.1% and HPV18 in 5.4%. Within the HPV-positive cases, 27.3% had multiple genotypes. All HPV-positive patients under the age of 45 years were positive only for HPV16. Conclusions HPV16 was the most commonly detected genotype in PeCa. HPV 31, 35 and 39 were infrequent; however, they were related to a single infection and P16INK4A overexpression; thus, they seem to be relevant in PeCa carcinogenesis. Our results suggest that P16INK4A overexpression could be useful for the classification of HPV-related PeCa. The role of multiple HPV genotypes in the development and prognosis of PeCa is still not completely understood. Thus, it is necessary to define criteria to establish reliable ways to classify HPV-related PeCa that could lead to optimal therapeutic approaches.

Penile squamous cell carcinoma is a rare malignancy seen more frequently in developing nations. Metastasis occurs in a predictable manner, with superficial lymph node involvement occurring first, followed by deep lymph node involvement, and then distant spread. Brain, lung, liver, and bone are the typical sites of distant metastasis. We present the unusual case of an 81-year-old man with penile squamous cell carcinoma requiring total penectomy who developed a confluent red to violaceous, indurated suprapubic plaque with satellite papules and bulky inguinal lymphadenopathy. The shield-like clinical presentation and infiltrating strands and cords on histology resembled carcinoma en cuirasse, a rare form of cutaneous metastasis frequently associated with breast cancer but not reported with penile squamous cell carcinoma.

Metastatic bone diseases are common in the advanced stage of numerous cancers, but rarely reported to be secondary from penile cancer. To date, there are only 9 cases of skeletal metastasis from penile cancer reported in literature worldwide. Herein, we report a rare case of the femoral neck metastasis secondary from penile carcinoma in a 35-year-old Chinese male. Based on the case study and more importantly, the literature review, we attempted to identify the clinical features of the metastatic bone diseases secondary from penile cancer.

Background: The high-risk human papillomavirus (HPV) infection represents one of the main etiologic pathways of penile carcinogenesis in approximately 30–50 % of cases. Several techniques for the detection of HPV are currently available including Polymerase chain reaction-based techniques, DNA and RNA in situ hybridization (ISH), p16 immunohistochemistry (IHC). The multiplex HPV RNA ISH/p16 IHC is a novel technique for the simultaneous detection of HPV E6/E7 transcripts and p16INK4a overexpression on the same slide in a single assay. The main aim of this study was to evaluate the discrepancy of p16 IHC expression relatively to HPV RNA ISH in penile cancer tissue. Methods: We collected a series of 60 PCs. HPV has been analysed through the RNA ISH, p16 IHC and the multiplex HPV RNA ISH/p16 IHC. Results: The multiplex HPV RNA ISH /p16 IHC results in the series were in complete agreement with the previous results obtained through the classic p16 IHC and HPV RNA scope carried out on two different slides. The multiplex HPV RNA ISH /p16 IHC showed that HPV positivity in our series is more frequently in usual squamous cell carcinoma than in special histotypes (19 out of 60 − 15 %- versus 6 out of 60 − 10 %-), in high-grade than in moderate/low grade carcinomas (6 out of 60 − 10 %- versus 4 out of 60 − 6.7 %-). In addition, our data revealed that in 5 out of 20 cases with p16 high intensity expression is not associated with HPV RNA ISH positivity. Conclusions: Our findings emphasize that the use of p16 as a surrogate of HPV positivity was unsuccessful in approximatively 8 % of cases analysed in our series. Indeed, p16 IHC showed a sensitivity of 100 % and a specificity of 71 %, with a positive predictive value (PPV) of 54 % and a negative predictive value of 100 %; when considering high intensity, p16 IHC showed a sensitivity of 100 %, a specificity of 89 %, with a PPV of 75 % and NPV of 100 %. Since HPV positivity could represent a relevant prognostic and predictive value, the correct characterization offered by this approach appears to be of paramount importance. [ABSTRACT FROM AUTHOR]

Penile carcinoma is rare neoplasm in western countries. In development countries can constitute more than 10–20% malignant disease in men. It is usually seen in men with poor standards of penile hygiene. The bot fly (Dermatobia hominis) is endemic in certainly regions such as Central and South America. Human infestation at nonendemic areas is difficult to diagnose and the penile localization is rare and makes the diagnosis more difficult. The authors describe a rare case of simultaneous association between penile carcinoma and myiasis treated both surgically.

Video endoscopic inguinal lymphadenectomy (VEIL), either by the classical or robot-assisted approach, is performed to manage inguinal lymph nodes in penile carcinoma. Coronary artery bypass graft (CABG) is common in the age group affected by penile carcinoma. Saphenous vein graft harvesting (SVGH) is done for CABG and may be associated with scarred subcutaneous planes hindering VEIL. A 65-year-old male was diagnosed with T2 high-grade penile carcinoma. He had undergone CABG eight years ago. He underwent robot-assisted VEIL. The initial subcutaneous space beneath Camper's fascia was created by finger dissection and further developed by balloon inflation. A small space was made with difficulty to insert the ports. Monopolar shears were used to make a sharp dissection to develop the subcutaneous plane, and scarring was present close to Camper's fascia. Multiple small venules were visible and managed with bipolar diathermy. The rest of the procedure was performed as usual. The console time and estimated blood loss were higher in the SVGH limb. The drain output was higher on the SVGH side. Both sides had six negative lymph nodes. Minimal skin duskiness was noted on the ipsilateral side, which healed without any sequelae. This is the first documented report of robot-assisted VEIL, post saphenous vein harvest for CABG. It is associated with a slightly longer procedure time and more blood loss, but a satisfactory oncological outcome. This report highlights the feasibility and safety of robot-assisted VEIL in post-CABG saphenous vein harvest status. [ABSTRACT FROM AUTHOR]

Since the seminal study of Hart and Helwig in 1975, there are few detailed pathological studies of lichen sclerosus (LS). The aims of this study were to provide a detailed histopathological description of penile LS, as well as to explore its relationship with penile intraepithelial neoplasia (PeIN) or invasive carcinoma. We evaluated 200 patients and designed a topographical approach for the histological evaluation focusing in alterations of the following anatomical layers: squamous epithelium, lamina propria, dartos, and corpus spongiosum. We documented the quantity and topographical location of stromal lymphocytes. The prevalent lesions found were epithelial hyperplasia, atrophy, PeIN, basal cell vacuolization, lamina propria sclerosis, and variable patterns of lymphocytic infiltration. Various unique patterns of stromal sclerosis were described: perivascular, globular, linear, and solid fibrosis/hyalinization; any of them were found to be diagnostic for LS. The variation in the topography and density of lymphocytes was determinant for the identification of LS morphological variants: lichenoid, band-like, lymphocytic depleted, and mixed. A major finding was the identification of the variant designated as lymphocytic depleted LS, which we considered as the morphological prototype of LS associated with penile neoplasia. The detailed description of this complex lesion presented in this study may help pathologists in practice to identify and better define LS. The identification of the special variants suggests a role of the stromal lymphocytes in the process of carcinogenesis. Confirmation of the observations with more studies is necessary to determine the significance of these findings. [ABSTRACT FROM AUTHOR]

Penile carcinoma is a relatively frequent health issue in the developing countries such as Africa, Asia and South America, usually affecting men aged between 50 and 70 years. It is a highly treatable disease in its early stages, but has serious physical and psychological consequences. Usually, penile carcinoma is located in the penile glans, in approximately half the cases, with the most frequent histological type being squamous cell carcinoma with its microscopic subtypes. A large number of risk factors have been reported for this disease, having a multifactorial etiology, HPV infection being one of the most important factors involved in its appearance. Out of the HPV DNA positive genital cancers HPV-16 is the most frequently found type in men, followed by HPV-18. The evolution of penile cancer includes two independent carcinogenic pathways, related or unrelated to HPV infection. There is limited data available in literature regarding HPV-related neoplasia, as well as on the efficacy of vaccination in men, with studies still ongoing. [ABSTRACT FROM AUTHOR]

Background: HDR brachytherapy of penis is suitable organ-sparing method of treatment for selected patients. Material and methods: A total of 28 patients were treated at the Department of Oncology and radiotherapy at University Hospital Hradec Králové between 2002 and 2020 for early penile tumor using high-dose rate brachytherapy (HDR brachytherapy), the total dose was 18 x 3 Gy, applied twice a day. Results: The median follow-up of patients is 92 months (3,7-219). Seven patients developed recurrence of the penile cancer (25%) with median time to recurence of 39 months (3.7-219). Six patients underwent partial amputation of penis without further recurence. Twenty patients are alive with a preserved penis, 19 of them are sexually active. Four patients died (1 patient of duplicate lung tumor, 3 of internal comorbidities). Five-year overall survival in our cohort is 96,4% (95% CI: 89,6-100,0%), penile cancer free survival 100%, five-year disease free survival is 77,7% (95% CI: 61,8-93,5%) and fiveyear survival without local reccurence is 81,1% (95% CI: 66,0-96,1%). Conclusion: Hyperfractionated interstitial high-dose rate brachytherapy with 18 times 3Gy per fraction twice daily is a promising method in selected patients with penile carcinoma and deserves further evaluation in larger prospective study. [ABSTRACT FROM AUTHOR]

Background: Approximately 50% of cases of penile carcinoma (PeCa), a rare neoplasm worldwide, are associated with human papillomavirus (HPV). However, the detection of HPV-DNA is not sufficient to consider it the etiological factor in the development of this type of cancer. Currently, the overexpression of P16INK4A is used as a surrogate biomarker of HPV carcinogenesis. Information on PeCa in Mexico is scarce, particularly regarding cases related to HPV and genotype frequency.Objective: To evaluate the presence of HPV, its genotypes, and the presence of multiple genotypes, and the expression of P16INK4A, as well as its clinical and histopathological parameters.Methods: For HPV-DNA detection and P16INK4A expression, we used the INNO-LiPA® test and immunohistochemistry, respectively.Results: Sixty cases of PeCa were evaluated, of which 75% were HPV-non-related histological variants. We found that 58.9% (33/56) of PeCa cases were HPV-DNA positive, while 30.9% of the cases evaluated (17/55) were positive for P16INK4A. HPV16 was the main genotype in 42.9% of the cases, followed by HPV52 in 7.1% and HPV18 in 5.4%. Within the HPV-positive cases, 27.3% had multiple genotypes. All HPV-positive patients under the age of 45 years were positive only for HPV16.Conclusions: HPV16 was the most commonly detected genotype in PeCa. HPV 31, 35 and 39 were infrequent; however, they were related to a single infection and P16INK4A overexpression; thus, they seem to be relevant in PeCa carcinogenesis. Our results suggest that P16INK4A overexpression could be useful for the classification of HPV-related PeCa. The role of multiple HPV genotypes in the development and prognosis of PeCa is still not completely understood. Thus, it is necessary to define criteria to establish reliable ways to classify HPV-related PeCa that could lead to optimal therapeutic approaches. [ABSTRACT FROM AUTHOR]

This article discusses pathological features of tumours of the male genital tract. Carcinoma of the prostate is common and represents an increasing burden to the NHS in terms of management and treatment. We focus on recent changes to grading and discuss issues around pathological diagnosis. Tumours of the testes represent the greatest success story of cancer treatment over the past several decades. We review the pathological features of the commonest tumours focusing on prognostic features. Carcinoma of the penis is rare but appears to be increasing in incidence. It requires more awareness amongst the public and general practitioners to prevent presentation at an advanced stage. We focus on pre-invasive lesions and on the pathological staging of this disease. [ABSTRACT FROM AUTHOR]

Per American Brachytherapy Society guidelines, cT1-2N0 penile cancers <4 cm in diameter are excellent candidates for curative brachytherapy. Using that criterion, we evaluated national patterns of care and predictors of use of radiation techniques using the National Cancer Database. The National Cancer Database was queried for men with cT1-2N0 penile cancers <4 cm in size. Comparative statistics for treatment modality were generated using bivariate logistic regression analysis. Among 1235 cases eligible for analysis, median age was 69 years. Median tumor size was 2.0 cm. 95.8% of men underwent surgery alone, with 91 (7.4%) undergoing radical penectomy, 673 (54.5%) partial penectomy, and 419 (33.9%) cosmesis-preserving surgical procedure. Only 4 (0.3%) men were treated with brachytherapy alone, 48 (3.9%) with external-beam radiation therapy (EBRT) alone, and 8 (0.6%) with EBRT after surgery. Surgical margins were positive in 118 (9.6%) patients, 14 of whom received adjuvant EBRT (11.9%) and two adjuvant brachytherapy (1.7%). There was no difference in demographic or clinical characteristics in groups treated with surgery vs. radiation (all p > 0.2). Age >70, lesions >2 cm, and T2 tumors were more likely to undergo non–organ-preserving therapy vs. radiation or a cosmesis-preserving procedure (all p < 0.05). The propensity-matched 5-year survival was not different between definitive radiation vs. surgery (61.6% vs. 62.2%, p = 0.70). Men with penile-preserving eligible lesions in the United States are overwhelmingly treated with surgery. Penile-preserving radiation techniques including brachytherapy and EBRT are underutilized and should be offered as curative interventions. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) infection is one of the most common sexually transmitted infections. HPV high risk (HPVHR) were HPV16,18 related with invasive penile carcinomas, and HPV low risk (HPVLR) were HPV6,11 related to anogenital warts. Male infection is usually asymptomatic that it would be explain increasing the incidence of HPV associated cancers. Identification HPV genotype is very important for predicting the development of the diseases, to be benign or malignant cancer. The objective of this study was to identify the genotype of HPV that infect men with anogential warts. This research used 12 biopsy specimens from men patient with anogenital warts at Outpatient clinic of Department Dermatology and Venereology, Dr. Soetomo General Hospital period 2016-2017. The specimens were diagnozed by pathologist and HPV gentoyping was done to detect 40 HPV genotype including HPVHR and HPVLR. The result showed that 58% (7/12) were positive for HPVLR and 42% (5/12) were positive for HPV LR/HR. The genotype HPV that infected men patient with anogenital warts is HPVLR (HPV6,11) and HPVHR (HPV18,51,52,82) with single infection of HPVLR or mutiple infection HPVLR/LR or HPVLR/HR. The infection of HPVHR would be develops to be malignant transformation. It suggested that HPV genotype needs to be checked the for the anogenital warts cases for predicting the development of the diseases. [ABSTRACT FROM AUTHOR]

Objective: To determine the incidence of penile intraepithelial neoplasia in the Netherlands using a nationwide histopathology registry and to discuss the nomenclature of premalignant penile lesions. Methods: Data from patients in the Netherlands diagnosed with a premalignant penile lesion between January 1998 and December 2007 were collected from the nationwide histopathology registry (PALGA); this database covers all pathology reports of inhabitants in the Netherlands. The premalignant lesions included were erythroplasia of Queyrat; Bowen's disease; bowenoid papulosis; mild, moderate and severe dysplasia; and carcinoma in situ of the penis. The terminology used in the pathological reports was translated to penile intraepithelial neoplasia. The grading was made analogous to that of vulvar premalignant lesions. Results: The PALGA database enrolled 380 patients with premalignant penile lesions. Severe premalignant lesions, penile intraepithelial neoplasia III, were found in 254 patients (67%), penile intraepithelial neoplasia II in 84 (22%) and penile intraepithelial neoplasia I in 42 patients (11%). Most lesions were located on the prepuce (45%), followed by glans (38%) and shaft (3%). The median age of patients with penile intraepithelial neoplasia was 58 years. Progression to malignant disease occurred (2% for penile intraepithelial neoplasia I vs 7% for penile intraepithelial neoplasia III) in 26 patients. Conclusions: Penile intraepithelial neoplasia is a rarely diagnosed condition. Because of the wide variation of terms used for premalignant intraepithelial neoplasia of the penis, we recommend restricting this nomenclature to penile intraepithelial neoplasia. [ABSTRACT FROM AUTHOR]

Androgen receptor (AR) is a member of the steroid and nuclear family receptor that acts as transcription factor. AR signaling plays pivotal role in the development and progression of prostate cancer. However, the role of AR in penile cancer (PeCa) is poorly explored. Our previous molecular studies unveiled frequent AR mRNA loss in PeCa, which was further predicted as a major driver alteration in this neoplasm. Herein, we assessed the AR protein expression in 59 usual PeCa tissues and 42 surrounding normal tissues (SNT) by immunohistochemistry using a tissue microarray. In a paired analysis, we found a total absence of nuclear AR expression in PeCa while 95.2% of SNT samples presented strong nuclear AR expression (P < 0.001). Interestingly, 17 of 42 PeCa presented weak or moderate cytoplasmic AR staining, contrasting with 5 of 42 SNT (P = 0.008). Increased levels of AR cytoplasmic expression were related with poor prognosis features including advanced clinical staging (P = 0.044), compromised surgical margins (P = 0.005), and pathological inguinal node status (P = 0.047). Furthermore, AR cytoplasmic expression was also related with shorter overall survival (P = 0.032). In conclusion, the frequent loss of nuclear AR protein levels suggests a potential function in PeCa development. Based on this result, the androgen deprivation therapy is not indicated for PeCa patients. In addition, the AR cytoplasmic expression found in a significant number of cases (40.5%) showed prognostic value and pathways activated by the non-genomic AR signaling may represent a promising therapeutic strategy. [ABSTRACT FROM AUTHOR]