Prostate cancer metastasis to the testis: an unexpected presentation of a solitary recurrence

Abstract

A 74-year-old man with a history of prostate cancer was referred to the urology team with a new left sided testicular lump. He had a background of prostate cancer 4 years previous which had been treated with external beam radiotherapy and androgen deprivation therapy, both of which had been completed. Concurrently, he also had evidence of biochemical recurrence of prostate cancer with a rising prostate-specific antigen (PSA). He underwent a left radical orchidectomy. Following histopathological analysis, this was found to be metastatic spread from his prostate cancer. Subsequent staging showed no evidence of metastatic spread elsewhere. The patient made a good recovery following surgery and his PSA levels returned to undetectable levels. He received no further treatment for metastatic prostate cancer.

Background

Prostate cancer is the most common malignancy diagnosed in men, representing 13% of all cancer cases diagnosed in the UK between 2015 and 2017. Due to modern widespread use of prostate-specific antigen (PSA) testing, the majority of those diagnosed have localised disease, while 17%–34% of patients with prostate cancer will have metastatic disease at diagnosis.¹ Of those diagnosed with localised disease, 16.9%–31.2% will have high risk disease, leaving them at significant risk of recurrent disease and subsequent metastatic disease.² In patients with high-risk disease, it has been demonstrated by Bolla et al that 10-year survival improved from 39.8% to 58.1% in patients receiving external beam radiotherapy (EBRT) combined with 3 years androgen deprivation therapy (ADT) compared with EBRT alone. In the same study, the risk of distant progression was 15% following radiation plus androgen suppression.³ The most common sites of metastatic spread of prostate cancer include bone, lymph nodes, liver and thorax.⁴ Despite their close proximity, metastatic spread to the testis from the prostate is a rare phenomenon. We describe a case of a patient with a history of high-risk prostate adenocarcinoma treated with EBRT and ADT, who presented with a new lump in his left testis which was diagnosed as metastases from prostate cancer after radical orchidectomy. The patient, at the time of writing, required no further treatment in the management of metastatic disease. The case highlights a rare presentation of metastatic prostate cancer. Clinicians should have a low index for suspicion for metastatic disease in the differential diagnosis of new testicular masses in older men, especially in those with a history of malignancy.

Case presentation

A 74-year-old man with a medical history of aortic stenosis, non-alcoholic fatty liver disease and polymyalgia rheumatica presented to his general practitioner (GP) with worsening lower urinary tract symptoms in 2015. As part of his workup, his GP carried out a PSA blood test and a digital rectal examination (DRE). His PSA result was 46.38 ng/mL and his DRE was suspicious for malignancy, and he was referred to our urology team for consideration of prostate cancer diagnostics. He underwent transrectal ultrasound-guided biopsies of his prostate and was subsequently diagnosed with Gleason 4+3 prostate adenocarcinoma. This was of microacinar type with perineural invasion, but no evidence of lymphovascular invasion, and no extracapsular extension. Staging at this time was carried out in the form of an MRI scan of his prostate and an isotope bone scan. Following these, and discussion at a regional multidisciplinary team (MDT) meeting, he was diagnosed as T3b NX M0 prostate adenocarcinoma—classified as high risk disease.⁵ He was given ADT for 3 years and received radical EBRT. He completed EBRT in November 2015. PSA had fallen to <0.03 in 2017 and he completed ADT in June 2018.

The patient represented to his GP in September 2019 with a new palpable mass on his left testis. An ultrasound scan of his testes was carried out which showed an area of mixed echogenicity within the left testis which was highly concerning for neoplasia. Earlier that year, follow-up PSA tests had shown evidence of biochemical recurrence with rises to 1.39 ng/mL and 2.27 ng/mL in July and September, respectively. He was subsequently re-referred to the urology team as a new testis lump of unknown origin. Tumour markers for testis cancer were within the normal range: LDH 193 U/L (normal range: 135–225 U/L), alpha-fetoprotein 2.7 kU/L (normal range: 0–10 kU/L), Total b-hCG <1.0 U/L (normal range: 0–5 U/L). Following clinical assessment, the patient underwent urgent left radical orchidectomy. The operation itself was carried out without any issues, and he was discharged the next day. The postoperative course was unremarkable.

Histopathological analysis was carried out on the testis and spermatic cord. The background testis was atrophic. The histology showed a tumour present within the testicular parenchyma and rete with extensive lymphovascular invasion and involvement of hilar vessels and hilar soft tissue (figure 1). Immunohistochemistry was performed which showed the tumour cells stained strongly and diffusely positively for AE1/3, NKX 3.1 and PSA (figures 2 and 3). CK7, CK20, TTF1, SAT B2, OCT 4, AFP, glipican 3, CD30, CD117, D24, HCG and CDX2 were negative. The morphological and immunohistochemical features were in keeping with metastatic prostate adenocarcinoma, suggestive of a mixture of microacinar and ductal components.

Figure 1.

2.5× magnification of prostate carcinoma infiltrating the rete testis and tunica.

Figure 2.

Positive immunohistochemistry staining by tumour cells for NKX3.1 (nuclei of prostate carcinoma cells positive).

Figure 3.

Positive immunohistochemistry staining by tumour cells for prostate-specific antigen (cytoplasm of prostate carcinoma cells positive).

Outcome and follow-up

The histopathological results were discussed at our local MDT and the patient was restaged in the form of a CT chest, abdomen and pelvis; a nuclear medicine bone scan and an MRI of his prostate. CT chest, abdomen and pelvis showed no evidence of disseminated malignancy; a repeat bone scan showed no evidence of bony metastases, and an updated MRI prostate showed an unremarkable, post radiotherapy prostate gland.

PSA has since returned to <0.03 ng/mL and the patient has not been recommenced on ADT. He will be followed up with 3 monthly PSA checks. His most recent PSA, 6 months post surgery, remained at <0.03 ng/mL. At the time of writing, the patient has required no further treatment for metastatic prostate cancer.

Discussion

Despite the close proximity of the prostate to the testis, metastatic spread of prostate cancer to the testis is rare. Metastatic disease to the testis in general is uncommon, outside of leukaemia and lymphoma. In 1972, Pienkos and Jablockow examined 24 000 autopsy reports and found an incidence of 0.06% of testicular metastases.⁶ Historically, the finding of metastatic spread of prostate cancer to the testis was incidental, found either at the time of subcapsular orchidectomy for hormonal manipulation therapy. Johansson and Lannes reported that about 4% of testicular metastases are detected incidentally during orchiectomy for advanced prostate cancer.⁷ In 2008, a review of 26 non-incidental cases of testicular metastases demonstrated the prostate to be the most common site of primary disease—with 11 cases. Of those cases, six had a known history of prostate cancer.⁸ In this case report, we describe a case of a patient with metastatic spread following EBRT and ADT. Other recent cases in the literature have described metastatic prostate cancer spread to the testes during follow-up after radical prostatectomy,^{9 10} and during hormonal treatment of known metastatic prostate cancer.^{11 12} We are aware that other centres may use prostate membrane specific antigen or choline PET CT imaging for further detection of metastases; however, due to unavailability in our unit, this has not been carried out at present.

The mechanism of spread of disease in these cases is poorly understood. Proposed mechanisms of spread of prostate cancer to the testis include retrograde venous extension, embolism, arterial embolism, lymphatics or endocanalicular spread.¹¹ Typically, the finding is a sign of advanced disease, with other reports describing it in conjunction with widespread metastases. In 1973, Weitzner described a case series whereby survival of 15 patients ranged from 6 to 18 months, with the majority surviving less than 1 year.¹³ Our case differs in this regard, as there were no other signs of metastatic disease on imaging, and biochemical markers have returned to undetectable levels. Admittedly, however, follow-up at time of writing has only been 6 months. While he remains high risk for recurrence, surgery of his solitary has delayed further systemic ADT.

In addition to history of disease and presentation, the age of the patient is relevant in this case presentation. The majority of cases of metastases to the testes occur after the sixth decade. This is in contrast with primary tumours of the testis, in particular germ cell tumours, which typically present in younger men.¹⁴ This observation suggests that new testicular neoplasms in older patients, especially those with a history of malignancy, should raise suspicion for possible metastases.

Learning points.

• Prostate cancer is the most common malignancy in men, with the majority of patients diagnosed with localised disease. In these patients, those with high-risk disease are at greater risk of progression to metastatic disease.

• Metastatic disease to the testes in general is rare. Prostate cancer metastases to the testes was historically an incidental finding at either autopsy or bilateral orchidectomy for management of metastatic prostate cancer.

• The mechanism of spread of prostate cancer to the testes is poorly understood; however, it has been described following radical prostatectomy, androgen deprivation therapy for metastatic disease, and in this case following external beam radiotherapy

• Metastatic disease to the testis should be considered in older patients presenting with new testicular lumps, especially those with a history of malignancy, particularly prostate cancer.