PSMA-PET Detection of Unusual Metastases in Castrate-Sensitive Prostate Carcinoma

Abstract

Prostate cancer (PCa) is a multifaceted, heterogeneous disease (with 7 molecular subtypes), which can metastasize to common sites, such as bone, lymph nodes, liver, and lungs. However, with PSMA PET imaging, rare sites of metastasis are increasingly discovered. We report 5 cases of unusual metastases in patients with castrate-sensitive PCa: solitary right inguinal nodal metastasis, solitary abdominal wall metastasis, penile shaft metastases, solitary perineum metastasis, and pleural metastases. These cases further support the use of PSMA-PET imaging in PCa monitoring, with the ability to detect solitary, small volume, and rare sites of metastases, which may not be apparent on conventional imaging.

FIGURE 1.

Axial fused ¹⁸F-PET/CT image demonstrating solitary right inguinal nodal metastasis after biochemical relapse 16 years after radical prostatectomy for pT2cN0 Gleason 3 + 4 = 7 intermediate-risk prostate adenocarcinoma, initially diagnosed at age 68. In this rare case, there were no pathological findings of lymphovascular involvement of obturator, internal, or external lymph nodes. This could be related to the soil-seed hypothesis,¹ or primary tumor secreted angiogenic growth factors (VEGFA/C, PDGF, FGF, HGF) altering peri-lymph node structure, before metastatic cell arrival, inducing lymphangiogenesis.² Reportedly, this can reduce antigen-presenting dendritic cell and lymph node T-lymphocytes.³ Alternatively, metastatic prostate cells may move as amoeboidal clusters, which do not classically metastasize via EMT. Only one other single inguinal node recurrence of prostate cancer (PCa) has been reported.⁴

FIGURE 2.

Axial fused ⁶⁸Ga-PSMA PET/CT image demonstrating intense tracer uptake in left rectus abdominal musculature, 5 years postradical robotic prostatectomy (showing extensive extracapsular extension) and salvage radiotherapy. This patient was diagnosed with pT3aN0 high-risk Gleason 4 + 5 = 9 prostate carcinoma with presenting PSA of 13 μg/L at age 71. Restaging ⁶⁸Ga-PSMA PET scan revealed solitary intensely avid focus at medial margin of left rectus muscle at level of pelvis, whereas MRI exhibited diffuse thickening of the correlating portion of the rectus sheath muscle with abnormal contrast enhancement and adjacent scarring, indicating probable tract of previously inserted port. Metastasis to the parietal abdominal wall is most often observed postsurgically, caused by laparoscopic procedures for tumor resection,^5,6 which is strangely uncommon, given the amount of such operations undertaken.

FIGURE 3.

Axial fused ⁶⁸Ga-PSMA PET/CT image demonstrating tracer avidity within penile shaft and right inguinal node, following prostatectomy and salvage radiotherapy, in a 69-year-old gentleman diagnosed with pT3aN0 Gleason 3 + 4 = 7 prostate adenocarcinoma with tertiary pattern 5. PCa cell metastases to the penis is considered extremely rare, accounting for less than 0.3% of cases.⁷ Mechanisms of penile metastases occur due to direct invasion from primary, iatrogenically (through instrumentation), retrograde venous flow, and lymphovascular dissemination.⁸ Retrograde venous flow is the most common mechanism of PCa metastases to the penis, due to communication between the prostatic plexus of Santorini and deep dorsal vein of the penis.⁸ Unfortunately, prognosis for PCa penile metastasis patients is extremely poor, and management is usually involved with improving quality of life versus morbid systemic/surgical management.

FIGURE 4.

Axial fused ⁶⁸Ga-PSMA PET/CT image demonstrating tracer avidity within the perineum, 5 years postprostatectomy and salvage radiotherapy, in a patient with pT2N0 Gleason 4 + 4 = 8 prostate carcinoma, diagnosed at age 67. He was treated with stereotactic radiotherapy, as the lesion was not easily amenable for surgical resection. To our knowledge, this is the first known report in the literature of a single perineal metastatic recurrence (without direct local invasion) from a primary PCa, postprostatectomy, and salvage prostate bed radiotherapy.

FIGURE 5.

Frontal image of ⁶⁸Ga-PSMA PET MIP, demonstrating multifocal avid right pleural metastases, in a 73-year-old gentleman with high-risk cT3N0M0 Gleason 3 + 4 = 7 adenocarcinoma, 7 years postdefinitive radiotherapy and 3 years androgen deprivation therapy. He was referred for video-assisted thoracoscopic pleural biopsy, which confirmed adenocarcinoma, with positive PSA and PSMA immunohistochemical stains. He was treated with androgen deprivation therapy and referred for consideration of systemic therapy. Isolated pleural involvement is considered a rare and adverse prognostic factor, occurring in approximately 2.3% to 5% of cases.^9,10