Introduction

Penile carcinoma is an uncommon malignancy, elucidating less than 1% of all male malignancies. Its occurrence varies worldwide; in high-income countries, the incidence of penile cancer ranges from 0.1 to 1 case per 100,000 men; the disease is significantly more common in lower- and middle-income nations, where the burden is much higher.1 In India, the frequency of penile cancer is anticipated to be about 0.8 cases per 100,000 individuals.2 Penile cancer typically appears as an ulcerative or proliferative lesion on the penis, most often in older men. In developing countries, delayed diagnosis is common, and patients often present with enlarged lymph nodes in both the groin and pelvic regions.3 Histopathological findings revealed that squamous cell carcinoma makes up about 90 to 95% of all penile cancer cases. Less prevalent variants include basaloid, verrucous, papillary, sarcomatoid, and condylomatous subtypes.4 Several factors increase the risk of developing penile cancer, including chronic inflammation, poor genital hygiene, urinary tract infections, penile injuries or tears, phimosis, human immunodeficiency virus infection, genital warts, and tobacco use.56 Human papillomavirus (HPV) types 16 and 18 are linked to nearly 50% of squamous cell carcinoma cases and are often associated with more favorable outcomes. The overall prognosis is largely governed by factors such as the cancer's stage, grade of the tumor, number of involvements of lymph nodes, and HPV status.7 The core for treating is amputative surgery; however, organ-preserving approaches may be contemplated for low-risk cases. Patients with large, inoperable tumors, significantly enlarged lymph nodes on both sides of the groin, or imaging evidence of pelvic lymph node involvement are typically applicants for neoadjuvant chemotherapy.8 Adjuvant chemotherapy is advised for patients with multiple enlarged lymph nodes on both sides of the groin showing extracapsular spread or when there is secondary involvement of pelvic lymph nodes.9 For metastatic penile cancer, palliative treatment typically involves platinum-based chemotherapy as the standard approach.10 This article aimed to explore the demographics, histopathological features, treatment-related toxicities, and clinical as well as survival outcomes in penile cancer patients who took systemic therapy. The prime goal was to evaluate key survival metrics, such as progression-free survival (PFS) and overall survival (OS), in histopathologically confirmed cases. Additionally, the study assessed clinical profiles, treatment approaches, and side effects associated with therapy. Given the limited data available on penile cancer in the Indian population, gaining deeper insight into disease patterns and treatment responses is crucial. Such knowledge can help improve treatment strategies and bridge current gaps in patient care.

Materials and Methods

A retrospective analysis was performed on patients diagnosed with histologically confirmed penile carcinoma diagnosed between April 2021 and December 2024, irrespective of disease stage. As this was a retrospective study, registration with a clinical trials registry was not necessary. This investigation was carried out in compliance with the ethical principles summarized by the Indian Council of Medical Research and the Declaration of Helsinki. No external funding was received for this study.

During the study period, individuals aged 18 years and older with biopsy-confirmed carcinoma of the penis, irrespective of disease stage, were included in the analysis. Relevant data, including baseline demographics, educational background, place of residence, presenting symptoms, disease stage, histopathological findings, precise treatment history, and rejoinder to therapy, were extracted from medical archives for evaluation.

Information on treatment modalities, including surgery, radiotherapy, chemotherapy, or a combination of approaches, was obtained from patient medical records. The treatment intent was classified as either curative or palliative, based on documented clinical decisions. Palliative treatment was defined as any intervention administered without curative intent. Disease staging was performed according to the American Joint Committee on Cancer–Tumor, Node, Metastasis 8th edition guidelines.

Results

Medical records of patients who received treatment at our institute during the study period were reviewed. The most common presenting symptoms included ulcerative-proliferative lesions (60%), pain (50%), dysuria (40%), and lymphedema (40%). The median age at diagnosis was 56 years (interquartile range: 49.25–59.25). Among the cohort, 90% (9 patients) had localized or locally advanced disease and underwent primary surgical intervention—8 patients (80%) received partial penectomy, while 1 patient (10%) underwent total penectomy. These patients subsequently received adjuvant chemotherapy and/or radiotherapy based on disease stage. One patient (10%) presented with metastatic disease at diagnosis and was started on palliative chemotherapy. A majority of patients had advanced tumor stages, with 60% classified as T3 or T4 and 90% showing nodal involvement (N + ), as detailed in Table 1.

Eight out of nine patients (80%) with node-positive disease received adjuvant radiotherapy to the nodal regions, while one patient (10%) did not complete the planned radiation. The median disease-free survival (DFS) among patients with nonmetastatic disease was 14 months (95% confidence interval [CI]: 12.61–15.38). Following disease progression, these individuals received palliative treatment, with a median PFS of 12 months (95% CI: 11.29–12.71) and a median OS of 28 months (95% CI: 24.9–31.09). Adverse events included grade ≥ 3 neutropenia in two patients (20%) and hypothyroidism in one patient. OS tended to decrease with more advanced disease stages. No treatment-related deaths were reported.

Discussion

Although penile carcinoma is considered an uncommon malignancy in highly developed, industrialized nations, its incidence remains notably higher in developing regions. It continues to pose significant challenges for radiation oncologists, medical oncologists, and uro-oncologists involved in its management. This single-center retrospective study aimed to evaluate the clinical characteristics, medicament regime, and survival results among patients diagnosed with carcinoma of the penis who received systemic therapy. The median age at diagnosis was 56 years, consistent with findings from other Indian studies.111213 In our study, the most frequently observed risk factors were smoking (40%), phimosis (20%), and balanoposthitis (20%). Penile carcinoma commonly presented as a pain-free ulcer or mass, while approximately one-third of patients reported dysuria. Notably, 70% of patients presented with clinically evident inguinal lymphadenopathy, which is higher than what is typically reported in existing literature.13 An Indian study reported that 70% of patients diagnosed with penile carcinoma were smokers, emphasizing that the disease predominantly affected older, uncircumcised men with a history of tobacco use.14 Another Indian study identified smoking as the most prevalent risk factor for penile carcinoma, observed in 27.5% of cases, which aligns with the findings of our study.3 Histopathological evaluation showed that 70% of cases were well or moderately differentiated squamous cell carcinomas, while poorly differentiated tumors accounted for 20%. Rare histological subtypes were observed in less than 10% of cases, aligning with findings reported in previous studies.12 A greater proportion of patients in our cohort presented with advanced disease, with 60% having higher T stages (T3 and T4) and 90% exhibiting nodal involvement. These figures are notably higher compared to reports from several other developing countries.15 In our analysis, patients with nonmetastatic penile cancer demonstrated a median DFS of 14 months (95% CI: 12.61–15.38). Following disease progression, these individuals received treatment with palliative intent, resulting in a median PFS of 12 months (95% CI: 11.29–12.71) and a median OS of 28 months (95% CI: 24.9–31.09); this aligns with findings from an Indian study by Noronha et al, which indicated a median OS of 33.8 months (95% CI: 17.2–not reached) for individuals treated with curative intent, and 11.4 months (95% CI: 9.53–23.3) for those managed with palliative therapy.13 Two patients (20%) had grade 3 or higher neutropenia, and one patient had hypothyroidism. No treatment-related mortality was observed. A retrospective analysis was undertaken in Thailand between the years 2007 and 2015, which included 70 patients, 32 with advanced stage III/IV cancer, also published a median OS of 29.3 months among those treated primarily with a combination of 5-fluorouracil and cisplatin, closely aligning with the survival outcomes observed in our study.16 One of the key strengths of our study lies in the multidisciplinary approach to patient management, where treatment decisions were made through collaborative discussions involving radiation oncologists, pathologists, medical oncologists, and uro-oncologists. This team-based strategy ensured consistent, consensus-driven care tailored to individual patient needs. However, the study is not without limitations. Its retrospective nature and single-center design may limit the generalizability of the findings. Additionally, HPV testing was not routinely performed at our institution, which restricted our ability to estimate the effect of HPV status on clinical results.

Conclusion

This study sheds light on the clinical characteristics and management outcomes of penile cancer, its rarity, and the therapeutic challenges. The data demonstrate that most of our patients presenting with advanced-stage disease experience poorer survival outcomes. It was found that inguinal lymph node metastasis is associated with reduced DFS. These findings reinforce the critical role of timely lymphadenectomy in optimizing patient outcomes. Given the higher prevalence of penile cancer in developing countries, our study underscores the pressing need for region-specific research and improved access to multidisciplinary care.