Evidence of anorectal involvement by prostate cancer on GA-68-PSMA-11 PET/CT portends inguinal nodal metastasis

Abstract

Biochemical recurrence was detected in a 68-year-old diagnosed with prostate adenocarcinoma 6 years previously (Gleason 4+4=8, grade group 4, T1bN0M0) status post radiation therapy and 2 years of androgen-deprivation therapy. The patient underwent transurethral resection of the prostate (TURP) for urinary retention with histology demonstrating recurrent prostate adenocarcinoma (Gleason 4+5=9, grade group 5). PSA was 22.95 ng/mL. ⁶⁸Ga-PSMA-11 PET/CT subsequently detected an isolated inguinal lymph node metastasis, hypothesized to have occurred via rectotumoral fistulation in the setting of prior pelvic radiation. This case highlights PSMA-targeted PET radiotracers as an essential tool in staging recurrent/metastatic prostate cancer, facilitating identification of atypical sites of metastatic disease.

Introduction

Lymph node metastases are present in 27-57% of clinically localized regional prostate cancer [[1], [2], [3]]. Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) has developed into an essential clinical tool in characterizing newly diagnosed and recurrent/metastatic disease. Specifically in the recurrence setting, PSMA-targeted PET radiotracers have demonstrated a high detection efficiency with high lesion-level positive predictive values [[4], [5]] – although numerous interpretive pitfalls have been described [6]. Prostate cancer metastases commonly involve obturator, presacral, lateral sacral, iliac, and paraaortic nodes [1,7]. While atypical routes of spread, such as inguinal lymph nodes [8,9], have previously been reported, isolated inguinal lymph node metastases on PSMA PET/CT are a rare finding, and uptake within such nodes would generally be considered unlikely to represent a site of prostate cancer [6]. When present, radiologists should attempt to identify underlying mechanisms that would explain inguinal nodal involvement, such as the presence of local invasion facilitating less common pathways for spread. We report a case of anorectal involvement portending isolated inguinal lymph node metastasis in a 68-year-old man with prostate cancer. Inguinal lymph node uptake on ⁶⁸Ga-PSMA-11 PET/CT was suggestive of isolated metastatic disease in the setting of a rising PSA and unusual imaging findings, which was subsequently confirmed intraoperatively and histologically.

Case report

The patient was a 68-year-old man diagnosed with prostate adenocarcinoma 6 years previously (Gleason 4+4=8, grade group 4, T1bN0M0) status post radiation therapy with 2 years of androgen-deprivation therapy (ADT) with leuprolide. One year following completion of radiation therapy and ADT, the patient’s PSA remained undetectable. However, 2 years following ADT, his PSA slightly increased to 0.15, which trended upwards over the subsequent 6 months to 2.13. PSA continued to trend upwards to 5.65 over the following year. The clinical picture raised concern for biochemical recurrence, now at 3 years post-therapy. Two months later, the patient underwent transurethral resection of the prostate (TURP) for urinary retention, and histology demonstrated recurrent prostate adenocarcinoma (Gleason 4+5=9, grade group 5). PSA had continued to trend upwards and was most recently 22.95 ng/mL at the time of the TURP procedure.

One month following TURP, the patient obtained a PSMA-targeted ⁶⁸Ga-PSMA-11 PET/CT at an outside hospital. While details regarding scanner model and uptake time are unavailable to our facility, the study was performed following the administration of 5 mCi of 68Ga-PSMA. Low-dose CT images were performed without contrast, and delayed imaging of the pelvis was not performed. The outside report described heterogenous uptake in an enlarged prostate and radiotracer uptake in a mildly enlarged right inguinal lymph node, measuring 1.6 cm in short axis.

Approximately 2 weeks later, the patient presented to our institution with urinary symptoms, chills, and sweats, and CT imaging at the time was suggestive of prostatitis with possible abscess. Repeat TURP that day demonstrated necrotic tissue as sequelae of recent TURP. While no evidence of abscess was identified intraoperatively, histology demonstrated scattered neutrophils and clusters of bacteria, compatible with prostatitis.

Following this hospitalization, the patient established care with our institution for management of his prostate cancer, and the previous outside facility’s PET/CT images were submitted for interpretation. Upon internal review, there were postprocedural changes following TURP, including the surgical resection margin along the inferior bladder and prostatic urethra, with fiducial markers and heterogenous prostatic uptake tracking along the bilateral peripheral zones and left anterior transitional zone to the prostatic apex where the greatest uptake was present (Fig. 1A, maximum lean-body-mass-corrected standardized uptake value, SUV_max, 6.5). A 1.6-cm right inguinal lymph node demonstrated uptake (SUV_max 8.8) without additional radiotracer-avid disease outside of the prostate (Fig. 1B,G). While the inguinal lymph node uptake would be unlikely to be metastatic disease in most patients, a second-opinion interpretation of the scan more definitively raised concern for metastasis based on additional CT findings. Those findings included intraprostatic and urinary bladder gas with partial obliteration of the rectoprostatic fat. Radiotracer uptake was present in a soft tissue attenuation, likely fistulous, tract extending from the posterior prostate to the rectum with SUV_max 5.3 (Fig. 1C). Prior imaging was unavailable for comparison to determine the chronicity of these findings. Subsequent ultrasound-guided core biopsy of the right inguinal node (Fig. 1D) demonstrated metastatic prostate adenocarcinoma (Fig. 1E,F).

Fig. 1.

Anorectal involvement by prostate cancer portends isolated inguinal nodal metastasis. (A) PET/CT demonstrating postprocedural changes with fiducial markers and heterogenous prostatic uptake. Abnormal radiotracer uptake is identified in an isolated 1.6-cm right inguinal lymph node (red circle, SUV_max 8.8) without additional radiotracer-avid metastatic disease. Heterogenous uptake was noted throughout the prostate (blue arrow, SUV_max 6.5). (B) Non-contrast CT demonstrating partial obliteration of the rectoprostatic fat (yellow arrow). (C) PET/CT demonstrating radiotracer uptake present in a soft tissue attenuation, likely fistulous, tract from the posterior prostate to the rectum with SUV_max 5.3 (green box). (D) Static image of the ultrasound-guided core biopsy of the right inguinal node (red arrowhead). (E) Hematoxylin and eosin stain with 40x magnification illustrating malignant cells with prominent nucleoli arranged in a cribriform architecture, consistent with pattern 4 prostate adenocarcinoma. (F) NKX3.1 stain showing that tumor cells were strongly positive for NKX3.1 expression, a specific marker of prostate epithelial origin. (G) Maximum intensity projection (MIP) PET image with physiologic uptake in the lacrimal and salivary glands, liver, spleen, kidneys, bladder, and bowel. Heterogenous uptake is demonstrated throughout the prostate (blue arrowhead) with isolated abnormal uptake in a right inguinal lymph node (red arrow).

Due to a history of erectile dysfunction, hot flashes, cognitive difficulties, and loss of muscle mass on prior ADT, the patient wished to minimize ADT moving forwards. He was initially managed with GnRH modulators with future consideration of androgen receptor pathway inhibitors. Stereotactic radiation therapy was deferred given prior definitive course of radiation with an overlapping field. The patient continued to salvage cystoprostatectomy with pelvic lymphadenectomy and ileal conduit urinary diversion with histology Gleason 5+5=10, grade group 5 prostate cancer involving the bladder dome (rpT2N0M1). Notably, intraoperatively the prostatic apex appeared tethered posteriorly to the rectum, confirming the imaging findings of a rectoprostatic fistula. All 11 resected regional pelvic lymph nodes were negative for metastatic disease.

Discussion

PMSA is a transmembrane glycoprotein expressed in prostatic ducts and is upregulated in prostate cancer cells. Therefore, that protein can act as a radiotracer target for identifying sites of prostate cancer involvement. While, traditionally, a combination of bone scan with CT and/or MRI has been utilized for staging and re-staging prostate cancer, PMSA PET/CT has developed into the most important imaging studies for evaluating for the presence of metastatic disease given a decidedly superior sensitivity to other modalities [10,11]. It is often utilized when biochemical recurrence is detected via rising PSA levels in order to define the extent of disease [4,5].

As demonstrated by this case, PSMA PET/CT is essential for detecting metastatic disease, particularly when there are atypical patterns of spread, and predicting risk of progression and mortality in patients with prostate cancer [1,7]. When interpreting PSMA PET/CT, physiologic uptake may be present in normal prostate tissue, salivary and lacrimal glands, small intestines, liver, spleen, and sympathetic ganglia. However, uptake in atypical locations should raise concern for malignancy [9]. Recurrent prostate cancer most often involves the prostate/prostate bed, as well as obturator, presacral, lateral sacral, iliac, and paraaortic nodes [8,9].

While inguinal lymph node metastases have been reported [6,[8], [9]], isolated inguinal lymph node metastases on PSMA PET/CT are rare. In fact, while a previously reported case of a single inguinal nodal metastasis identified on contrast enhanced CT exists, osseous metastases were present in addition to obliteration of the fat pad intervening between the prostate, bladder, and seminal vesicles, thus suggesting more systemic involvement [12]. Woo et al. found that 48.1% of patients with prostate cancer may have inguinal lymph node involvement. However, only 2.5% of patients in their 79-patient cohort had isolated inguinal lymph node metastases with cases either demonstrating rectoprostatic fistula formation or diffuse metastatic disease [3]. Therefore, when atypical sites of disease are identified, additional distant metastases or aberrant lymphatic drainage pathways as sequelae of surgery or radiation should be sought.

The presence of enlarged inguinal lymph nodes in the setting of prostate cancer provide a unique challenge to the radiologist in that the finding is nonspecific, but should be carefully scrutinized given the risk of involvement. Our case is unique in that a single site of metastatic disease outside of the pelvis was identified on PSMA-PET/CT with a probable atypical drainage pathway enabled by the radiotracer-avid tethering of the prostatic apex to the rectum. While the differential diagnosis may include a reactive lymph node, metastasis of a synchronous/metachronous primary, or sarcoidosis, isolated metastatic prostate cancer was favored given the avidity and obliteration of the rectoprostatic fat.

It is hypothesized that the probable mechanism for this patient was rectotumoral fistula formation with drainage to the inguinal lymph node. We suggest that a fistula may have developed as post-radiation or post-surgical sequela, establishing an atypical drainage pathway for tumor. While uncommon, atypical lymphatic drainage pathways should be considered when interpreting PMSA PET/CT, particularly with direct evidence of anorectal involvement, confirmed by the tethering of the prostatic apex to the rectum. Indeed, perhaps the most important lesson from this case is that findings concerning for radiotracer-avid, direct invasion of the anal canal or distal rectum should raise the level of suspicion of any abnormal inguinal uptake, particularly in the setting of biochemical recurrence, detected via a rising PSA.

The high detection efficiency and positive predictive value of typical sites of prostate cancer [4,5] must be weighed against the known pitfalls of PSMA-targeted PET/CT interpretation [6], and ultimately tissue sampling was crucial in confirming the proposed metastasis. Challenges with PMSA PET/CT vary, but include limitations of PET spatial resolution and potential uptake in a wide range of benign and malignant, non-prostatic tumors, Paget's disease, sarcoidosis, cerebral infarctions, and bone fractures [6]. Additionally, disease near the prostate gland may be obscured by the excreted radiotracer in the adjacent urinary bladder, and the timing of imaging following radiotracer administration may influence measured SUV findings. This means that for equivocal findings, delayed imaging may be helpful as radiotracer accumulates intracellularly in cancer cells [6].

Despite these challenges, PMSA PET/CT has earned a role as a key instrument in staging and re-staging prostate cancer. While an isolated, mildly enlarged lymph node could raise concern for metastasis, without other suggestive findings it is nonspecific with the differential diagnosis including a reactive lymph node versus a metastasis from a synchronous primary, particularly given the atypical location. However, the high specificity of ⁶⁸GA-PSMA-11 PET/CT coupled with the recognition of key CT findings enabled a timely diagnosis in this case, thus expediting patient care. Therefore, familiarity with PMSA PET/CT interpretation is of vital importance as the role for PMSA PET/CT continues to expand in the future.

Conclusion

PSMA-targeted PET/CT is an essential tool in identifying and characterizing metastatic prostate cancer, influencing prognosis and therapeutic management. This case underscores the importance of this imaging modality in identifying atypical routes of metastasis, particularly given the high detection efficiency and positive predictive value of PSMA PET/CT.

Patient consent

Written informed consent was obtained from the patient for the publication of this case report and accompanying images.