Clinical analysis of secondary penile cancer: a case series at a tertiary referral center in China

Dear Editor, Secondary penile cancer is an extremely rare condition that refers to the metastasis of other malignancies to the penis. There are limited reports on secondary penile cancer in Asian populations, and perceptions about this disease are extremely scarce. We reviewed and analyzed the data of patients diagnosed with secondary penile cancer based on the pathological findings at Peking University First Hospital in Beijing, China, aiming to expand the clinical reference for this rare disease. We included six patients (Patients 1–6) in our case series from January 2000 to October 2022, and the specific individual information is shown in Supplementary Table 1 and Supplementary Figure 1. The vast majority of the patients were elderly men over 65 years old (5/6, 83.3%) and the mean ± standard deviation of age was 62.8 ± 14.8 years (range: 33–72 years). All patients had a previous history of tumors at sites other than the penis. Of these six patients, three patients had metastases from colorectal cancer to the penis, two patients had a primary tumor of bladder urothelial carcinoma, and one patient had a primary tumor of prostate origin. The time from the primary tumor to the appearance of metastases in the penis ranged from 1 year to 7 years. Four out of the six patients had metastatic carcinoma of the penis as the first symptom. Only 2 patients developed symptomatic tumor metastases in other organs before presenting with penile metastases.Supplementary Table 1: Specific clinical characteristics of the case seriesSupplementary Figure 1: Representative pathological findings in patients with secondary penile cancer. (a) Patient 1: moderately differentiated adenocarcinoma from rectal cancer; (b) Patient 2: moderately differentiated adenocarcinoma from sigmoid cancer; (c) Patient 4: poorly differentiated adenocarcinoma from prostate cancer; (d) Patient 6: invasive transitional cell carcinoma G3 from bladder cancer, with a proportion greater than 50% of moderately to poorly differentiated squamous carcinomas.This study was a retrospective observational study and did not conduct any additional intervention to all included individuals. This study was approved by the Ethics Committee of Peking University First Hospital (Approval No. 2015977). Written informed consent was obtained from all the patients for the publication of this article and any accompanying images. An incidentally discovered penile mass was the most common presenting symptom for patients in this case series and was the main reason for driving patients to seek medical attention. In five patients, definite hard penis masses could be palpated. Penile masses are variable in number and can be either solitary or multiple. The penile masses also varied in size and were less regular in morphology. Except for one tumor of Patient 4 that had a smooth surface and good skin mobility, the location of other patients’ tumors was fixed and the skin mobility was poor. Moreover, the vast majority of the masses were located in the penile body. The postoperative pathological findings in this case series showed that the tumors could infiltrate the corpora cavernosa and surrounding fat, as well as the corpora cavernosa of the urethra, often with extensive necrosis. Penile pain was another common symptom in this case series. There were 4 patients (Patient 1, Patient 2, Patient 5, and Patient 6) with painful penile masses, but their masses were not accompanied by redness and hyperemia. With the gradual growth of his penile mass, Patient 4 had difficulty in urinating and the urinary stream was diminished. For some patients, malignant priapism is a crucial manifestation of secondary penile cancer.1–5 The clinical manifestations of secondary penile cancer are also closely related to the nature of the primary tumor. For tumors of colorectal origin, necrotic tissue in penile masses can be accompanied by mucus. For patients with urothelial carcinoma-derived secondary penile cancer, the tumor tended to first involve the urethra and then invade the urethral cavernous body and patients can present with hematuria or can have bloody secretions and discharge from the urethra. Patient 5 was admitted to our hospital 2 years after cystectomy because of bleeding from the urethral orifice that persisted for 2 months and urethroscopy revealed multiple papillary-like tumors in the anterior and posterior urethra. The size of multiple tumors ranged from 1.3 cm × 0.7 cm × 0.6 cm to 1.8 cm × 1.5 cm × 1.3 cm, they had infiltrated into the muscular layer of the urethral cavernous body, and no tumor was found at the urethral transection. Even though the urethral cavernoma was absent, the tumor later invaded the patient’s corpora cavernosa. Patient 6 presented to the clinic with penile pain with a small amount of yellowish fluid and occasional bloody fluid flowing out from the urethral orifice. Ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI) can detect the size of penile tumors and their infiltration into surrounding tissues. Positron emission tomography-computed tomography (PET-CT) can further determine the malignant tendency of tumors through the tumor’s metabolic status. Some characteristic imaging manifestations are shown in Figure 1.Figure 1: Representative imaging findings in patients with secondary penile cancer. (a) Contrast-enhanced CT findings in Patient 1: tumor in the glans penis and corpus cavernosum. (b) Contrast-enhanced CT findings in Patient 3: tumor in the corpus root cavernosum. (c) MRI findings in Patient 4: T2W1 signal of urethral cavernous body decreased, and DWI high signal and fascia low signal around urethral cavernous body disappeared; the boundary between penile cavernous body and urethral cavernous body was not clear. The red arrow points to the tumor tissue of the penis. CT: computed tomography; MRI: magnetic resonance imaging; DWI: diffusion-weighted imaging; T2WI: T2-weighted imaging.Direct spread, retrovenous metastasis, arterial metastasis, lymphatic metastasis, and iatrogenic surgical metastasis may lead to secondary penile cancer.6,7 Most of the cancers that cause metastasis to the penis arise from the urogenital organs (69%, mainly the prostate and bladder), followed by the gastrointestinal tract (19%, mainly the rectum and sigmoid colon).5 In the present case series, the pathologic findings of Patient 3’s prior treatment unequivocally indicated that his rectal tumor had invaded the vasculature. Patient 1’s tumor presented in the glans penis and corpora cavernosa, consistent with the regional distribution of the dorsal venous return of the penis. Patient 2 had metastatic adenocarcinoma of the liver, suggesting that the tumor may have invaded the inferior vena cava system. Patient 4 had penile metastasis after receiving transurethral resection of the prostate (TURP). We speculate that the tumor cells on the surface of the resectoscope came in and out of the urethra through the lens after the resectoscope device had contacted the prostate tissue during the operation, causing the spread of the tumor. Despite the poor prognosis of secondary penile cancer,8 early diagnosis and individualized comprehensive treatment may be beneficial for some patients. Penile resection and urinary diversion surgery are currently the main surgical modalities for the treatment of secondary penile cancer. Most of the patients had already had bone and pelvic lymph node and other multiple metastases when the penile metastasis was found. It is necessary to adopt comprehensive treatment means, such as radiotherapy and chemotherapy, to target the biological characteristics of the primary tumor. In early case reports, most patients died within 6 months to 1 year after the detection of penile metastasis.9,10 However, in our case series, all patients survived at least 2 years after the discovery of penile metastasis. The specific treatment regimens and prognoses received by the patients are shown in Supplementary Table 2. Personalized chemotherapy regimens tailored to the different circumstances of patients may be of importance. The development of novel chemotherapeutic agents and the guarantee of negative surgical margins at a relatively early stage offer new hope for prolonging patient survival.Supplementary Table 2: Treatment and prognosis of the case seriesAUTHOR CONTRIBUTIONS XYL conceived the study and wrote the manuscript. XYL, CRX, XJ, ZPZ, TYC, and ZKG participated in the study design, data collection, and analysis. JL supervised the study. All authors read and approved the final manuscript. COMPETING INTERESTS All authors declare no competing interests. ACKNOWLEDGMENTS This work was financially supported by the National Natural Science Foundation of China (grant No. 8207032402). Supplementary Information is linked to the online version of the paper on the Asian Journal of Andrology website.