PSMA-PET/CT-avid metastatic prostate cancer to the penis

Abstract

Penile metastases from prostate cancer (PC) are rarely reported in the literature. Most commonly diagnosed due to presentation with malignant priapism and other urinary symptoms or from findings on clinical examination, prognosis has been reported to be poor. The authors outline a case of penile metastasis from advanced PC. Initially treated with neoadjuvant androgen deprivation therapy for locally advanced PC, this patient displayed upfront castrate resistance, and subsequent prostate-specific membrane antigen positron emission tomography revealed penile metastatic deposits. The patient was treated with external beam radiotherapy, and worsening urethral stricture disease resulted in the placement of a suprapubic catheter.

Background

Penile metastatic deposits from metastatic prostate cancer (mPC) are extremely rare, and few case reports exist in the literature. Diagnosis has been equated with poor prognosis, with Kotake et al finding 41% of patients in a 25-patient review succumbing to mPC within 6 months of diagnosis of penile metastasis. Another 41% of patients in this cohort had an unknown outcome, and therefore mortality may have been higher.¹ Hızlı and Berkmen reviewed 305 cases of penile metastatic deposits from various primary malignancies and found that the most common symptom was malignant priapism, with other presentations secondary to acute urinary retention, penile nodules, ulceration, perineal pain, oedema, dysuria and hematuria.² To the best of the authors’ knowledge, with the exemption of single-case clinical images published by Vadi et al,³ the literature has not previously described incidental penile metastasis diagnosed on prostate-specific membrane antigen positron emission tomography (PSMA-PET), and this raises the question of whether earlier diagnosis and treatment may lead to better outcomes than the previously reported poor prognosis.

Case presentation

This 69-year-old man presented to his local medical officer with new-onset dysuria and nocturia. Serum PSA was 76 ng/L and a referral was made to the outpatient urology clinic. He had a medical history significant for type 2 diabetes mellitus, hyperlipidaemia, gastro-oesophageal reflux disease and persistent microcytic anaemia. Examination revealed atrophic testes, and a non-tender, firm, locally invasive, clinically T4 prostate gland. Urine microscopy revealed no organisms, serum alkaline phosphatase was low at 32 U/L, and renal function was unremarkable with a creatinine of 74 μmol/L and an estimated glomerular filtration rate (eGFR) of 90 mL/min. An ultrasound showed a 63 mL prostate gland and postvoid residual volume of 60 mL with no other abnormalities detected. Bone scintigraphy performed by the local medical officer showed no evidence of bone metastases. The patient was commenced on leuprorelin with 4 weeks of bicalutamide cover, and a PSMA-PET/CT was organised.

PSMA-PET/CT revealed an avid prostate primary and extensive locally invasive disease with bilateral seminal vesicle involvement, contiguous PSMA-avid enhancing soft tissue thickening along the right mesorectal fascia and right pelvic sidewall consistent with direct tumour invasion, bilateral internal iliac metastatic lymph nodes and mild right hydroureteronephrosis. There were no PSMA-avid osseous metastases detected. A referral was made to radiation oncology.

At routine blood examination 2 months postcommencement of androgen deprivation therapy, the patient was noted to have worsening renal function with a creatinine of 169 μmol/L and an eGFR of 35 mL/min. He was also noted to have a serum PSA of 235 ng/L (figure 1) with an undetectable serum testosterone level. Non-contrast abdominopelvic CT revealed bilateral hydroureteronephrosis to the level of the vesicoureteric junctions with a non-distended bladder, and the patient was scheduled for emerging bilateral ureteric stent placement.

Figure 1.

PSA trend with treatment, depicting early castrate resistance in this patient. ADT, androgen deprivation therapy; EBRT, external beam radiation therapy; PSA, prostate-specific antigen.

Cystoscopy revealed tumour invasion into the trigone and obscured bilateral ureteric orifices. Loop resection of the tumour overlying the trigone was performed and specimen was obtained for histological subtyping, and bilateral ureteric orifices were exposed. Left retrograde ureteric stent placement was performed; however, right retrograde ureteric stent placement was unsuccessful, and the patient subsequently underwent antegrade right ureteric stent placement. Renal function continued to recover to a serum creatinine of 91 μmol/L and an eGFR of 73 mL/min 3 weeks later.

Histology revealed Gleason 4+5=9 prostate cancer (PC), with predominant ductal adenocarcinoma, without neuroendocrine immunostaining positivity. The patient went on to complete 60 Gy/20# of high-dose palliative external beam radiotherapy to the pelvis, and serum PSA 4 weeks postcompletion fell to 52 ng/L. Bicalutamide was reintroduced and serum PSA at a further 3 months was 24 ng/L. The patient reported urinary urgency and urge urinary incontinence with nocturia on review and uroflow studies showed a Qmax 5.1 mL/s with a 34 mL voided volume, and postvoid residual of 335 mL. Symptoms improved with the introduction of prazosin and surgical intervention was not required. Endoscopic assessment of the urethra at 3 months of stent replacement reported a normal urethra with a partially occlusive trilobar prostate at 3 months and a tight urethra with no fixed stricture at 6 months.

Interval abdominopelvic CT at 5 months postradiotherapy showed interval reduction of the pelvic sidewall lymphadenopathy and no evidence of new or distant metastatic disease. However, serum PSA on combined androgen blockade at 7 months postcompletion of radiotherapy began to rise again, to 83 ng/L, and a progress PSMA-PET/CT revealed new widespread PSMA-avid osseous metastatic lesions to the sacrum, right femoral head, posterior acetabulum, ischial tuberosity, inferior pubic ramus and right scapula spine. PSMA-PET/CT also revealed new intense PSMA avidity in the shaft of the penis (figure 2). Enzalutamide was commenced, and a further short course of 30 Gy/10# palliative radiotherapy was delivered to the patient’s penis, sacrum and pelvic bony metastatic lesions. Serum PSA 3 months postcompletion of radiotherapy fell to 57 ng/L.

Figure 2.

Sagittal and axial prostate-specific membrane antigen positron emission tomography slices highlighting the incidental finding of penile metastatic prostate cancer.

Outcome and follow-up

Routine endoscopic retrograde ureteric stent change at 14 months from initial diagnosis and 5 months after further radiation noted dense urethral stricture disease extending from the proximal penile urethra to the bulbar urethra. Urethral dilatation was performed and a catheter was placed for 1 week, with a successful trial of void and postvoid residual of 20 mL following this. Again, the patient’s serum PSA began to rise on enzalutamide to 140 ng/L 1 week postcatheter removal and at 6 months postradiotherapy. An interval PSMA-PET/CT was organised, which showed reduced PSMA avidity within the base of the penis extending to the midshaft. It also noted decreased PSMA avidity in the bilateral iliac lymph nodes. Interval development of new PSMA-avid metastases to the C7 vertebral body, T7 transverse process, soft tissue nodule deep to the right supraspinatus muscle and increased avidity in the right scapula spine metastatic deposit were noted. A further 8 Gy/1# was delivered to the thoracic spine and right shoulder, and plans were made to commence docetaxel.

The patient continued to report lower urinary tract symptoms, and an interval urinary tract ultrasound showed a 199 mL postvoid residual with ongoing bilateral hydronephrosis with appropriately placed ureteric stents. Renal function was noted to show a creatinine of 130 μmol/L and an eGFR of 47 mL/min, and decision was made to place a suprapubic catheter and replace bilateral ureteric stents in preparation for docetaxel.

Discussion

Metastatic deposits to the penis are rare, and the few reports available in the literature show that it is associated with an aggressive disease process with a poor prognosis. Vadi et al published images of 68 Ga PSMA-PET/CT and uptake of 177 Lu-PSMA in a single case without detailed patient clinical course information or patient outcomes, and detailed patient history and outcomes are needed in the literature to further understand this novel early diagnosis of penile metastasis and its implications on management. The literature reports penile metastatic deposits diagnosed on clinical examination and, to the best of the author’s knowledge, no reports exist detailing the outcomes of mPC with incidental penile metastases found on PSMA-PET/CT. The Gleason 4+5=9 PC in our patient did indeed show aggressive features with upfront castrate resistance and progressive metastatic deposits despite enzalutamide. It is currently unknown whether early treatment of incidental metastatic deposits will equate to a survival advantage in this patient. However, after 18 months, our patient is presently still alive, preparing for chemotherapy after failed androgen manipulation.

Learning points.

• While penile metastatic deposits secondary to prostate cancer are rarely reported in the literature, the advent of prostate-specific membrane antigen positron emission tomography (PSMA-PET) may lead to more reports of incidental cases and broaden our understanding of the pathogenesis of penile metastases.

• Penile metastases reported in the literature have previously been diagnosed on clinical examination. It is unknown if earlier diagnosis on PSMA-PET/CT and treatment before clinical signs develop would equate to a survival advantage.

• This case adds to the literature, and to date, this patient’s metastatic prostate cancer (mPC) has also shown aggressive features in line with other reports of mPC to the penis.