Prostate cancer metastasis to the testis: case report

Introduction

Prostate cancer (PCa) is one of the leading cancers affecting men. According to the World Health Organization (WHO), in 2018 there were 1.3 million new cases with 359,000 associated deaths. Secondary tumors to the testis are rare; only 4% of patients with PCa will develop secondary metastases to the testis during their progression.

Possible routes of spread include retrograde venous spread through the spermatic vein, arterial embolism, lymphatic spread through para-aortic lymph nodes, through the vas deferens, transperitoneally through a patent processus vaginalis, and direct invasion.

The time from diagnosis to the appearance of testicular lesions is 2.5 years. Once testicular metastases are diagnosed, the prognosis is poor, and their appearance is usually a sign of advanced disease.

Case report

A 71-year-old hypertensive male was diagnosed with Gleason 7 (3+4) prostate adenocarcinoma by transrectal prostate biopsy and an initial total prostate-specific antigen (PSA) level of 12.1 ng/ml. Classified as having unfavorable intermediate-risk prostate cancer, he underwent a failed radical prostatectomy in a private setting in 2008 for an unknown cause. Only bilateral pelvic lymphadenectomy was performed, with a negative result for adenocarcinoma. He received salvage radiotherapy to the prostate bed and regional nodes. He maintained undetectable PSA levels for 10 years.

During his oncological follow-up, he presented with disease progression with bone metastatic activity identified by bone scintigraphy, for which reason he was referred to our medical center for evaluation and follow-up (2022). Because this patient’s treatment was performed at an institution affiliated with ours, the authors declare that they are unaware of other details of his treatment and follow-up. Our institutional approach began in 2022.

At our medical center, we identified a total PSA of 66.54 ng/ml (previous antigen levels are unknown). The institutional PET/PSMA showed tumor activity in the axial and appendicular skeleton (SUVmax 4.47), including the thoracic vertebral bodies, as well as the right iliac bone and both femurs (SUVmax 3.26) (Fig. 1). Based on these findings, the patient was classified as clinical stage IV disease.

Figure 1. PET/PSMA showing tumor activity in the right femur (thick longitudinal arrow) as well as a right testicular tumor (thin transverse arrow).

In 2022, the patient presented with progressive growth of the right testicle with no other symptoms. Testicular ultrasound revealed a heterogeneous nodular lesion suspicious for malignancy (Fig. 2), with the contralateral testicle within normal range.

Figure 2. Testicular ultrasound revealing a heterogeneous nodular lesion in the right testicle suspicious for malignancy.

After suspicion of a second primary tumor, a right radical orchiectomy was offered. The pathology report concluded metastasis of poorly differentiated adenocarcinoma (Fig. 3).

Figure 3. Histological image of the radical orchiectomy showing poorly differentiated acinar adenocarcinoma.

He received multiple lines of treatment, including prednisone with abiraterone and docetaxel (2022), cabazitaxel and enzalutamide (2023), and radium 223 for 6 cycles (2023). He presented with progressive PSA elevation despite multiple options. After radical orchiectomy, there was a slight decrease, however, this was transient (Fig. 4).

Figure 4. Progressive PSA elevation over time with multiple lines of treatment. The blue arrow represents the time at which testicular metastasis was identified.

Finally, the patient’s functional status progressively deteriorated over time and he died at the end of 2023 due to causes related to his oncological disease.

Discussion

Prostate cancer (PCa) is one of the leading cancers affecting men¹. The development of metastatic disease is one of the main causes of morbidity in PCa². The main sites of metastatic involvement include bones, lymph nodes, lungs, and liver¹.

With the exception of infiltration by leukemia and lymphoma, secondary tumors to the testis are rare³. The first documented case of testicular metastasis (TM) was described in 1935⁴. Testicular tumors, based on their origin, can be classified as primary and secondary; primary tumors are more common and tend to occur in younger individuals¹, although testicular non-Hodgkin lymphoma represents the most common primary testicular cancer in men over 60 years of age^5,6.

Metastatic disease to the testes is uncommon due to the blood-testicular barrier and lower scrotal temperature, conditions that may not favor the growth of non-native cells at this site¹. Only 4% of patients with PCa will develop secondary metastases to the testes during their course³.

Current literature reports approximately 200 cases of PCa that have developed metastases to the testes. Published case reports suggest that such MTs may present asymptomatic for up to 6 years after PCa diagnosis. The estimated mean time from initial diagnosis to testicular involvement is 4.1 years, with a range from 0 to 15⁷.

Routes of spread include venous extension through the spermatic vein, arterial embolism, lymphatic extension via the para-aortic lymph nodes, via the vas deferens, transperitoneally through a patent processus vaginalis, and direct invasion¹. A possible combination of all the aforementioned routes has been suggested. Bubendorf studied the metastatic route in 1,589 patients diagnosed with PCa at postmortem autopsies, 35% of whom had hematogenous metastases⁸.

TMs can be clinically indistinguishable from primary testicular tumors. Radiological diagnosis using scrotal ultrasound is challenging, as the findings mimic primary tumors, particularly mixed germ cell tumors^6,7.

Computed tomography combined with positron emission tomography (PET/CT) targeting prostate-specific membrane antigen (PSMA), a transmembrane protein overexpressed in PCa cells, has revolutionized imaging in recent years. This study uses short-lived radionuclides, for example, gallium-68 in the form of [68Ga]Ga-PSMA-11, demonstrating high sensitivity for tumor localization and suspected sites of metastasis after biochemical recurrence⁹.

Histologically, TMs are usually similar to the primary prostate tumor, presenting as glandular, cribriform cells without affecting the seminiferous tubules¹. They can also manifest as a nodular or destructive pattern, affecting and replacing these tubules⁸. Positive immunohistochemical staining for prostate-specific acid phosphatase is often found in these patients, which could help differentiate metastases from primary cancers². However, with the introduction of luteinizing hormone-regulating hormone (aLHRH) agonists, orchiectomy has been almost completely abandoned, and therefore, detection of this type of disease has become even rarer¹⁰.

Once TM is diagnosed, the prognosis is poor, and its appearance is usually a sign of advanced disease¹¹. The average time from diagnosis to the appearance of testicular lesions is 2.5 years. The prognostic implications remain controversial, as fewer than 200 cases have been published in the literature⁵. Due to the rarity of the event, the true long-term impact on overall survival and cancer-specific survival is unknown; The few studies currently available are presented as case reports or small series; therefore, no statistically robust study exists to provide treatment recommendations.

To assist with the decision-making process and patient management, we believe it is important to consider the clinical status, biological characteristics of the tumor, and PSA levels throughout the course of the disease.

Conclusion

MT in PCa is an extremely rare event, and distinguishing it from primary tumors can be difficult. Although there are common sites of metastasis, metastases can occur in uncommon locations. Due to the lack of recommendations in these cases, individualized treatment is required for each patient.

Funding

The authors declare that funding was not received for this study.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical considerations

Protection of humans and animals. The authors declare that no experiments involving humans or animals were conducted for this research.

Confidentiality, informed consent, and ethical approval. The authors have followed their institution’s confidentiality protocols, obtained informed consent from patients, and received approval from the Ethics Committee. The SAGER guidelines were followed according to the nature of the study.

Declaration on the use of artificial intelligence. The authors declare that no generative artificial intelligence was used in the writing of this manuscript.