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ANTICANCER RESEARCH 30: 1747-1750 (2010)

Solitary Testicular from Cancer: A Rare Case of Isolated Recurrence after Radical

STEFAN JANSSEN1, JOACHIM BERNHARDS2, ARISTOTELIS G. ANASTASIADIS3 and FRANK BRUNS1

1Department of Radiation Oncology, Hannover Medical School, Hannover, Germany; 2Department of Pathology, Robert Koch Krankenhaus Gehrden, Germany; 3Department of Urology, Großburgwedel Hospital, Germany

Abstract. Background: The prognosis of spread of prostate cancer to the testis is commonly accepted (PC) is mainly determined by the presence or absence of as a sign of advanced disease and is often accompanied by metastases. An isolated testicular metastasis of PC is rare. multiple metastases to other organs, especially to the skeletal Case Report: A 71-year-old patient with PC presented with system (4). an increased serum prostate-specific antigen (PSA) level of We report the case of a 71-year-old patient who presented 2.07 ng/ml two and a half years after radical prostatectomy. with a solitary testicular metastasis of prostate cancer two Assuming a local recurrence in the prostatic fossa, local and a half years after prostatectomy. The patient remains free radiotherapy with 64.8 Gy was performed. Unfortunately, the of disease two years after unilateral . PSA level rose again, accompanied by a swelling of the left testis approximately one month after radiotherapy. A Case Report unilateral orchiectomy was then performed, presenting a testicular metastasis of the PC. After orchiectomy, the PSA A 71-year-old Caucasian male consulted his family doctor decreased to <0.07 ng/ml. Two years later, the patient is still complaining of haematospermia. Because of a rising serum tumour-free. Conclusion: Careful clinical follow-up of prostate-specific antigen (PSA) level of 7.66 ng/ml a prostate patients with rising serum PSA level is important to biopsy was performed one month later and a locally advanced recognize isolated, locally treatable metastastic disease. In prostate tumour was detected. Neoadjuvant particular, rare metastatic sites such as the testis or the deprivation (goserelin 10.8 mg monthly injection, additional epididymis should be taken into account before treatment of 50 mg/d for the first three weeks) was then biochemical recurrence is initiated. started for three months, followed by a radical prostatectomy including pelvic lymphadenectomy. Histopathology showed Prostate cancer continues to be a major health problem in a cribriform adenocarcinoma of the prostate with a Gleason developed countries. Approved approaches to prostate cancer score of 3+3=6. Because of an infiltration of the left seminal include radical prostatectomy, radiotherapy, endocrine vesicle and the surrounding fat tissue, the tumour stage was treatment, and watchful waiting, depending on the risk pT3b pN0 M0 G2 R0, corresponding to an UICC stage III. category (1, 2). was complicated by a deep venous thrombosis of the The prognosis of prostate cancer is mainly determined by vena poplitea, and anticoagulation with phenprocoumon was the presence or absence of metastases. In particular, prostate initiated for six months. cancer synchronously or metachronously metastasizing to the Two and a half years later, the PSA level rose from <0.07 testis is unusual and reports of these kinds of metastasis were ng/ml to 2.07 ng/ml, indicating a biochemical recurrence. more frequent in the past, when this kind of neoplasm was Because no metastases were detected at this time, external often treated with bilateral orchiectomy (3). The metastatic beam radiotherapy of the prostatic fossa was performed, with a total dose of 64.8 Gy (1.8 Gy, five times a week). Besides mild acute irradiation side-effects, the treatment was well tolerated. Correspondence to: Stefan Janssen, MD, Department of Radiation One month after completing radiotherapy, the PSA level Oncology, Hannover Medical School, Carl Neuberg Straße 1, 30625 rose to 3.08 ng/ml. At this time, the patient complained of a Hannover, Germany. Tel: +49 5115322731, Fax: +49 5115323796, e-mail: [email protected] progressive, painful swelling of his left . He had no urinary symptoms. The lower pole of the left testicle was Key Words: Testicular metastasis, isolated recurrence, prostate painful on palpation. The scrotal skin showed no evidence of cancer, prostatectomy. inflammation. The ultrasound of the testis (Figure 1) revealed

0250-7005/2010 $2.00+.40 1747 ANTICANCER RESEARCH 30: 1747-1750 (2010)

Figure 1. Ultrasound of the left testis in two planes showing a large 31.5×18×19.5 mm, inhomogeneous, mainly liquid mass with solid portions in the peripheral area of the caudal pole.

Figure 2. Adenocarcinoma with cribriform pattern of growth reveals in situ extension in otherwise atrophic testicular tubuli. H&E stain, ×20. a 31.5×18×19.5 mm mass at the lower pole of the left testicle, with solid and liquid formations. A unilateral orchiectomy was then performed. Macroscopic examination of the operative Routes of metastatic spread to the testis are discussed specimen revealed a greyish-white irregular tumour in the controversially. Bubendorf et al. suggest that there might be testis, without extension to the periorchial tissues. At a backward metastatic pathway though veins from the histological examination, an adenocarcinoma with focally prostate additionally to the classical haematogenous tumour cribriform pattern of growth was found which revealed mainly spread via the vena cava. Overall, there are four proposed an in situ extension in the testicular tubuli (Figure 2). Focally, mechanisms for the spread of the lesions to the testis: a however, invasive growth through the tunica albuginea and retrograde venous extension, a retrograde lymphatic into surrounding tissues was found. Initially, a primary tumour extension, arterial embolism, and through the lumen of the of the testis was discussed, but immunohistochemistry with an (5). The occurrence of a deep vein thrombosis, antibody for PSA revealed strong positivity in the tumour cells although after surgery, could possibly indicate a pathway (Figure 3), and the diagnosis of metastasis of prostate cancer through retrograde venous extension in the presented case. in the testis was established. The epididymis and the spermatic Most cases of prostate carcinoma in the literature describe cord showed no infiltration. other metastatic sites besides the testis, for instance in the After orchiectomy, a computer tomography of the chest skeletal system or disseminated locations (5). But there are and abdomen revealed no other metastatic lesions. The PSA also cases of solitary metastasis to the testis or epididymis level dropped to 0.07 ng/ml (Figure 4), and the patient without any other metastases (7, 8). remains free of biochemical and clinical recurrence after two As there are numerous definitions of biochemical recurrence years. after radical prostatectomy (9), we followed the recommendation of the American Urological Association Prostate Guideline Panel Discussion which defines a biochemical recurrence as two consecutive PSA level values above 0.2 ng/ml after radical prostatectomy. Testicular metastases of prostate cancer are unusual. The first Particularly in cases of raised but low PSA levels, salvage reported case of local metastasis was described in 1935. In a radiotherapy of the prostatic fossa increases biochemical control large autopsy study of patients older than 40 years, 19316 and disease-free survival of patients with biochemical recurrence routine autopsies were performed from 1967 to 1995 (5). (1). In this case of a PSA level above 2 ng/ml, radiotherapy of Bubendorf et al. analysed the reports from the 1589 patients the prostatic fossa was carried out because we had no evidence with prostate cancer: 35% of them had haematogenous of any metastases at that time and the patient explicitly wished to metastases, most frequently involving the bone (90%), lung be treated with irradiation. (46%) and liver (25%); metastases in the testes were found In our case, diagnostics showed no evidence of other in 0.5% only (5). Nevertheless, prostate cancer is the most tumour spreading at the time of diagnosis of the testicular common tumour which metastasizes to the testis (15%); metastasis. The persisting low serum PSA level below the infrequently lung tumours, melanomas and colon or kidney cut-off level, the lack of clinical symptoms and the patient’s tumours also spread to the testis. About 15% of testicular good general condition confirmed the long-lasting tumour- metastases occur bilaterally (6). free status.

1748 Janssen et al: Isolated Testicular Metastasis from Prostate Cancer

Figure 4. Chronological course of PSA level (cut-off level 0.07 ng/ml) 1: Initial diagnosis (Dec 2002); 2: shortly after prostatectomy (Feb 2003); 3: biochemical recurrence (Nov 2005); 4: semicastration (Feb 2006).

Figure 3. Immunohistochemistry of intratubular tumour formation with an antibody to the prostate-specific antigen (source: Dako Cytomation) reveals strong positivity (dark cytoplasmatic staining). Counterstaining: hematoxylin, ×20. 5 Bubendorf L, Schopfer A, Wagner U, Sauter G, Moch H, Willi N, Gasser TC and Mihatsch MJ: Metastatic patterns of prostate cancer: An autopsy study of 1589 patients. Hum Pathol 31: 578- 583, 2000. Conclusion 6 Manikandan R, Nathaniel C, Reeve N and Brough RJ: Bilateral testicular metastases from prostatic carcinoma. Int J Urol 13: This case report highlights the need for careful clinical 476-477, 2006. follow-up of patients with prostatic cancer. As well as a local 7 Anastasiadis AG, Ebert T, Gerharz CD and Ackermann R: recurrence after prostatectomy or metastasis in the typical Epididymal metastasis of a prostatic carcinoma. Urologia Internationalis 60: 124-125, 1998. locations, one should also include rare metastatic sites such 8 Deb P, Chander Y and Rai RS: Testicular metastasis from as the testis and para-testicular structures in follow-up carcinoma of prostate: Report of two cases. Prostate Cancer evaluation when the serum PSA level rises. Therefore, the Prostatic Dis 10: 202-204, 2007. involvement of an urologist is mandatory in the follow-up of 9 Cookson MS, Aus G, Burnett AL, Canby-Hagino ED, D’Amico prostate cancer patients. AV, Dmochowski RR, Eton DT, Forman JD, Goldenberg SL, Hernandez J, Higano CS, Kraus SR, Moul JW, Tangen C, References Thrasher JB and Thompson I: Variation in the definition of biochemical recurrence in patients treated for localized prostate cancer: The American Urological Association Prostate 1 Jereczek-Fossa BA and Orecchia R: Evidence-based radiation Guidelines for Localized Prostate Cancer Update Panel report oncology: Definitive, adjuvant and salvage radiotherapy for non- and recommendations for a standard in the reporting of surgical metastatic prostate cancer. Radiother Oncol 84: 197-215, 2007. outcomes. J Urol 177: 540-545, 2007. 2 Koukourakis MI and Touloupidis S: External beam radiotherapy for prostate cancer: current position and trends. Anticancer Res 26: 485-494, 2006. 3 Kırkali Z, Reid R, Deane RF and Kyle KF: Silent testicular metastasis from carcinoma of the prostate. Br J Urol 66: 205- 207, 1990. 4 Patel SR, Richardson RL and Krols L: Metastasis of cancer to Received March 22, 2010 the testis: A report of 20 cases and review of the literature. Revised April 27, 2010 J Urol 142: 1003-1005, 1989. Accepted April 27, 2010

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