Sacral Radiculoplexopathy Caused by Direct Perineural Spread of Carcinoma Prostate Diagnosed in Ga-68 PSMA PET/CT

Introduction

Carcinoma prostate is the second-most common malignancy in men, accounting for about 14.1% of all new cancer cases in the world and 6.3% of all diagnosed cancer cases in South Central Asia. Carcinoma prostate accounts for 6.8% of cancer mortality globally and 3.1% of cancer mortality in South Central Asia among men.[1] The incidence of prostate carcinoma is higher in countries of high-socioeconomic status when compared to countries of lower socioeconomic status. For localized disease, the 5-year survival rate is almost 100%. However, it regresses to 28% in the case of metastatic disease.[2] The common sites of metastatic involvement include lymph nodes and bones. Visceral spread is also not uncommon. However, direct spread of tumor along the adjacent nerves is an uncommon yet rarely reported phenomenon. We present one such unusual case of carcinoma prostate, which presented with recurrence in the surgical bed, involving the adjacent sacral nerve roots and extending into the neural foramina, causing sacral plexopathy, and identified by gallium-68 prostate-specific membrane antigen positron emission tomography/computed tomography (Ga-68 PSMA PET/CT).

Case Report

A 69-year-old male who presented with increased frequency of micturition in 2017 was found to have elevated serum prostate-specific antigen (PSA) of 40 ng/mL. On further evaluation, multiparametric magnetic resonance imaging (MRI) showed a PIRADS 5 nodule in the left lobe of the prostate, extending from base to apex. Transrectal ultrasound-guided biopsy of the prostate revealed adenocarcinoma with Gleason score 4 + 4, following which the patient underwent robotic-assisted radical prostatectomy with bilateral extensive pelvic lymph node dissection. Histopathology revealed multifocal lesions in bilateral lobes with involvement of margin and bilateral seminal vesicles and no evidence of perineural invasion (PNI) or nodal involvement. Postoperative Gleason score was 4 + 5. The patient was started on antiandrogen therapy with bicalutamide and triptorelin, followed by radiotherapy to the local site (64.8 Gy in 36 fractions) and was on regular follow-up. Ga-68 PSMA PET/CT was performed in July 2019 and October 2021 in view of increasing serum PSA on subsequent follow-ups (from 0.41 ng/ml to 0.88 ng/ml with a doubling time of 3 months), which showed no evidence of disease recurrence. He was started on abiraterone, followed by doralutamide. His serum PSA in 2023 raised further to 3.9 ng/ml with a doubling time of 5 months. The patient developed low-grade lower back pain associated with paraesthesia in the posterior aspect of the thigh – Score 3 according to 0–10 Numeric Pain Rating Scale. Ga-68 PSMA PET/CT done in December 2023 revealed Ga-68 PSMA avid nodular enhancing lesions in the prostate bed, along the left lateral aspect of mesorectal fascia with involvement of left lower sacral nerve roots (S3 to S4) suggestive of local recurrence [Figure 1]. In the corresponding MRI, these lesions were T2-hyperintense with significantly restricted diffusion, and S3 and S4 nerve roots appeared thickened and hypointense in the T2-sequence [Figure 2]. The patient underwent external beam radiotherapy for the local recurrence of the tumor, and serum PSA value on 12-week follow-up declined to 2.3 ng/ml and the patient improved symptomatically on clinical assessment – Score 1 according to 0–10 Numeric Pain Rating Scale.

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Figure 1 Gallium-68 prostate-specific membrane antigen positron emission tomography/computed tomography (Ga-68 PSMA PET/CT) images demonstrating direct perineural spread of recurrent carcinoma prostate. Serial axial sections of Ga-68 PSMA PET/CT fusion images demonstrate Ga-68 PSMA avid lesion in prostate bed (A1; red arrow) suggestive of local recurrence which extends into left S2–S4 sacral nerve roots (A2; green arrow) upto sacral foramina (A3; blue arrow). Corresponding PET only images are illustrated as (B1-B3). Sagittal section images (C1 And C2) illustrate Ga-68 PSMA avid local recurrence of carcinoma prostate (red arrow) extending into left sacral nerve roots till sacral foramina (blue arrow). (D) Illustrates maximum intensity projection image showing contiguous involvement of sacral nerve roots (green arrow) till sacral foramina (blue arrow) from site of local recurrence (red arrow), Red, blue and green arrows represent specific areas of disease involvement as follows: red - prostate bed, green - sacral nerve roots, blue - sacral foramina

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Figure 2 Magnetic resonance imaging (MRI) images demonstrating direct perineural spread of recurrent carcinoma prostate. MRI images demonstrate T2-hyperintense lesion in prostate bed (red arrow) with thickened and hypointense left S3 and S4 nerve roots (green arrow), reaching up to sacral foramina (blue arrow) (a). Corresponding diffusion weighted imaging sequence (b) Significantly restricted diffusion in prostate bed (red arrow), left S3 and S4 nerve roots (green arrow), reaching upto sacral foramina (blue arrow), Red, blue and green arrows represent specific areas of disease involvement as follows: red - prostate bed, green - sacral nerve roots, blue - sacral foramina

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Discussion

The most common routes of prostate cancer spread are locally to seminal vesicles, through lymphatics to pelvic or abdominal lymph nodes and hematogenously to bone.[3] Visceral spread to the lung, liver, and adrenal gland can occur but is uncommon. PNI within tumor is commonly noted in head and neck malignancies, pancreatic, gall bladder, colorectal, and prostate cancer. In carcinoma prostate, 7%–43% of biopsy specimens have shown PNI, whereas 77%–93% of prostatectomy specimens have shown PNI. PNI is considered an independent unfavorable prognostic factor for carcinoma prostate.[4] However, direct perineural spread to adjacent nerve roots is very rare in prostate cancer and only few cases have been reported till now, involving adjacent lumbosacral plexus.[5] The sensory afferent nerve fibers from the prostate reach S2–S4 nerve roots through the hypogastric nerve, pelvic plexus, and pelvic nerves. Although the precise process of direct perineural spread to sacral nerve roots remains unknown, one plausible theory is that, a tumor from prostate can enter the lumbosacral plexus through these nerve fibers, through endoneurium. Hematogenous or lymphatic spread to nerve roots from the primary or recurrent prostate lesions is unlikely due to the blood-neuron barrier present in the perineurium and the absence of lymphatic supply to the endoneurium.

Clinical presentation of the perineural spread of carcinoma prostate could be sensory, motor or autonomic symptoms of specific nerve roots involved, such as weakness, paraesthesia, erectile dysfunction, and bowel and bladder abnormalities. Patients presenting with such complaints can mimic intervertebral disc prolapse, radiation neuritis, or cord compression due to vertebral metastases. MRI and Ga-68 PSMA PET/CT can differentiate intervertebral disc prolapse and cord compression from the rest. Possible MRI findings in cases of perineural spread are thickening and T2-hyperintensity of involved nerve roots. Ga-68 PSMA PET/CT can detect the perineural spread easily due to higher lesion-to-background contrast. On review of the literature, we found 11 such cases of carcinoma prostate with lumbosacral plexopathy been reported.[678910] All 11 cases were evaluated with MRI, whereas three cases were further evaluated using PET/CT, as done in this case. Ten out of 11 cases had motor and sensory deficits, 3 out of 11 cases had bowel or bladder irregularities, whereas this case presented with isolated sensory deficits [Table 1]. A few of the cases mentioned above also underwent F18-Fluorodeoxyglucose and C11-Choline PET/CT, whereas this is the first case to be evaluated using Ga-68 PSMA PET/CT, which proved the ability to identify perineural spread in carcinoma prostate. Prompt identification of this uncommon condition with common clinical symptoms is mandatory as it modifies the management and prognosis of the patient.

Conclusion

Among carcinoma prostate patients who present with complaints of lower back aches, sensory-motor deficits or autonomic dysfunction, the direct perineural spread of lumbosacral plexus should be suspected in addition to other common causes, and imaging features suggesting direct perineural spread should be carefully evaluated. Ga-68 PSMA PET/CT is a useful imaging tool in identifying such atypical presentation of carcinoma prostate.