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A 79-year-old man with a 12-year history of clinically localized prostate cancer presented to a hospital with a urethral stricture.

He had developed radiation cystitis and low-grade non-invasive urothelial carcinoma of the bladder some time after he received proton therapy following his prostate cancer diagnosis. In the process of prepping the patient for cystoscopic dilation of his urethral stricture, the nurse detected a mass on his right testicle.

The patient's prostate cancer was diagnosed in 2008 at age 67, when an abnormal nodule on the left apex area was identified on a digital rectal exam (DRE). At that time, yearly prostate-specific antigen (PSA) and DRE were recommended for men ages 50 to 70, as per American Urologic Association guidance.

When the patient was diagnosed, his serum PSA level was 3.3 ng/mL, but DRE detected a left-sided firm 1-cm nodule at the base. A biopsy was performed, which identified three cores of Gleason score 3+3 adenocarcinoma of the prostate. He started proton therapy 3 months later. From 2008 to 2019, yearly PSA test results remained less than 0.2 ng/mL, and given his low disease risk, no imaging was performed.

In 2020, when the testicular mass was detected, the patient underwent scrotal ultrasound, which showed a 5.5 × 3.5 × 2.5-cm heterogeneous mass with internal calcifications.

Markers of testicular cancer were negative. Clinicians performed a radical orchiectomy; pathology findings identified prostatic adenocarcinoma, acinar type, with evidence of lymphovascular invasion at the margin of the spermatic cord. His PSA level at this time was 0.34 ng/mL, and a fluciclovine PET/CT scan did not reveal any other areas of disease.

The patient was in good health and had a life expectancy of more than 10 years. After consultation with clinicians, he opted for combined androgen deprivation therapy (leuprolide 45 mg intramuscularly every 6 months) and androgen signaling inhibitor treatment (apalutamide [Erleada] 240 mg orally daily), which clinicians noted has shown the best long-term results in metastatic castration-naive prostate cancer. This treatment will continue indefinitely, provided his PSA level continues to respond appropriately. His most recent PSA level was <0.014 ng/dL in October 2021, and the patient is maintaining a good response.

Discussion

Clinicians of a solitary prostate cancer metastasis to the testis, which was detected incidentally during a preoperative examination, noted that this patient's metastasis "would not have been detected by conventional biochemical monitoring."

Typically, a rising PSA level indicates a recurrence of prostate cancer. According to patients with positive bone scans indicating biochemical progression after radical prostatectomy had an average PSA level of 61.3 ng/mL (range 1.3-123).

The group also suggested that the ability of fluciclovine PET/CT to detect the cancer's biochemical recurrence was "broadly proportional to prescan PSA," detecting recurrences in 31% of patients with PSA levels between 0 and 0.5 ng/mL, and in 79% of patients with PSA levels greater than 1.0 ng/mL, in the . Thus, the higher the PSA level, the more effectively PET detects recurrence.

"Although rare, metastasis can occur in the setting of very low or even undetectable PSA," the case authors noted. of 4,091 men with prostate cancer found that 46 patients had metastases -- most commonly to the bone, liver, and retroperitoneal lymph nodes -- despite PSA levels less than 2 ng/mL, and levels that were undetectable in 22%.

Most of these patients were asymptomatic, similar to the case patient. However, the risk factors present in that patient population, such as Gleason scores greater than 7, atypical histologic variants, and locally advanced tumors, were absent in the case patient.

"Metastatic prostate cancer, absent these risk factors, not to mention metastasis to the testicle, is extremely rare," the authors wrote. "The capacity of regular physical examination without specific indications to identify what would have been a life-threatening disease underscores its importance in clinical practice."

According to a , no other cases of prostatic adenocarcinoma accompanied by a Gleason score of 6 and a PSA level <1 ng/mL at diagnosis of testicular metastasis have been reported, they noted, suggesting that their patient's cancer recurrence despite his low PSA levels "may be explained by a clonal shift in the original tumor, which could lead to the proliferation of de-differentiated prostate cancer cell lines that have lost the ability to produce PSA."

Overall, metastasis of prostate cancer to the testicle has been reported in fewer than 200 published cases.

"Our current case is a reminder that there are always exceptions," the authors wrote, suggesting that even an apparently low-risk prostate cancer patient may have abnormalities detectable with physical examination.

"PSA velocity, or the change of PSA level over a given time interval, has a central role in the detection and diagnosis of prostate cancer, and its recurrence after treatment," they added. In addition to the testicular mass found on examination, this patient presented with an "additional, albeit subtle, abnormality -- although his PSA level remained very low, the most recent value prior to metastatic disease had started to increase from 0.110 to 0.341 ng/dL. This change was the most significant increase between post-treatment PSA values."

Even in cases considered low risk, surveillance for prostate cancer should be continued after treatment, the authors recommended. "Although rare, recurrence and metastasis can occur in patients with low and even absent post-treatment PSA."

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