Prostate Artery Embolization in the Setting of Prostate Cancer: Review and Opinion

Abstract

Prostate Artery Embolization (PAE) is a novel minimally invasive angiographic technique that has been used effectively to treat men with lower urinary tract symptoms (LUTS) from benign prostatic hyperplasia (BPH). However, applications of PAE for men with prostate cancer have been minimally studied. This review serves as an update on the status of PAE in men with prostate cancer, as well as a discussion of emerging indications.

Plain Language Summary

Prosate artery embolization (PAE) is done by interventional radiologists to help men who have urinary symptoms from an enlarged prostate. This article discusses how PAE is used to help men who have prostate cancer as they consider different treatments and side effects of these treatments

Introduction

In 2021 the Center for Disease Control and Prevention (CDC) reported that over 236,000 new prostate cancers were diagnosed ¹ and accepted definitive treatments included surgery or radiation. ² Life expectancy, baseline urinary and sexual function, and expected degree of urinary and sexual function decline after treatment inform the shared decision making between the treating physician and the patient for the selection of the appropriate modality of treatment. Urinary functional decline after definitive radiotherapy (RT) has been reported in less than 10% of men. ³ However, some studies have shown that Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or greater genitourinary (GU) toxicity may be as high as 33% ⁴ with toxicity driven by dose delivered to the urethra, bladder and prostate. Furthermore, studies have shown that men with enlarged prostates may have an increased risk of acute GU symptoms post RT ⁵ and that there is an increased risk of long term GU toxicity and urinary functional decline in those who have baseline moderate to severe lower urinary tract symptoms (LUTS) as defined by International Prostate Symptom Score (IPSS) or American Urologic Association (AUA) scoring.

Prostate artery embolization (PAE), first reported in 1999, is an angiographic procedure performed by interventional radiologists focused on restricting prostatic blood flow at the level of the capillaries for the purposes of inducing ischemic necrosis in the peri-urethral transition zone (TZ) ⁶ (Figure 1: pre/post PAE with TZ necrosis). The cellular death results in relief of prostatic pressure from hypertrophic prostate nodules in the peri-urethral TZ leading to improvement of LUTS. After the initial case reports were published, several protocol studies were performed to validate the safety and efficacy of PAE in men with benign prostatic hyperplasia (BPH).^7,8 These studies showed that PAE resulted in >90% of men experiencing significant LUTS improvement (ie, LUTS improvement from the severe category to the mild category on IPSS or AUA questionnaire) at 12 weeks after PAE ⁷ and an average of 25%–30% reduction in prostate volume at the same time frame. ⁸ In 2017, the FDA approved the embolic material for the indication of “symptomatic BPH” ⁹ and in 2023, the American Urologic Association (AUA) added PAE to the guidelines as an evidence-based option for men with medically refractory LUTS and “large” prostates. ¹⁰

Figure 1.

Comparison of pre- and post-PAE images demonstrating peri-urethral necrosis (“black hole” phenomenon). (A): Pre-embolization, axial post-contrast T1 fat-saturated (FS) large field of view (FOV) MR images demonstrate homogenous enhancement throughout the prostatic parenchyma, notably within the peri-urethral transition zone (TZ) (white arrow). Baseline prostate volume in this patient was 180 cc. (B): 12 weeks post-embolization, axial post-contrast T1-FS large FOV MR images demonstrate peri-urethral necrosis with “black-hole” appearance that represents devascularized prostatic parenchyma. 12-week post PAE volume in this patient was 66 cc, representing 63% prostate volume reduction.

While much has been published on the utility of PAE in men with LUTS from BPH without a concurrent diagnosis of prostate cancer, little has been published on the indications and role of PAE in men with prostate cancer. Therefore, the goal of this review is to (1) report the literature to date with respect to the utilization of PAE in men with prostate cancer and (2) discuss the emerging indications for PAE in these men.

PAE in Men with Prostate Cancer: Clinical Outcomes

Very few studies have been published regarding clinical outcomes after PAE in men who have prostate cancer. A 2019 study by Malling et al ¹¹ reported on the clinical efficacy of palliative PAE in men who had severe LUTS and retention from locally advanced prostate cancer. The study demonstrated moderate clinical improvement after PAE: 1/6 men experienced resolution of urinary retention. However, the remaining 5 men had a 12-point IPSS reduction. Chen et al ¹² studied the outcome of PAE in 9 men with refractory prostatic hematuria from locally advanced prostate cancer and reported that hematuria improved in the short term in 6/9 (67%) patients, however 2 of these men had recurrent hematuria within 60 days. Our group also published our experience evaluating clinical efficacy of PAE in men with medically refractory post-radiation prostatitis/chronic GU toxicity. ¹³ This study demonstrated that approximately 90% of men had clinical improvement in LUTS, similar to findings reported above from studies that evaluated PAE in the BPH population. While the data is limited, these results suggest a promising alternative for these men.

These studies demonstrate that the PAE is safe in the setting of locally advanced prostate cancer. However, clinical efficacy is (ie, the ability for PAE to improve LUTS and/or resolve hematuria) is modest and therefore patient expectations should be adjusted accordingly.

PAE in Men with Prostate Cancer: Oncologic Outcomes

A handful of studies have been published with respect to oncologic outcomes after PAE in men with prostate cancer. Although sample size was small, an excellent prospective study by Mordasini et al. ¹⁴ evaluated the oncologic efficacy of PAE in 12 men who had PAE prior to prostatectomy. The objective of the study was to assess the percentage of cellular necrosis in the index lesion after PAE and after prostatectomy and showed that only 2/12 index lesions demonstrated complete necrosis, while 5/12 demonstrated partial necrosis; also of note, secondary cancer foci were found in all patients. Another study from Frandon et al ¹⁵ evaluated the feasibility of PAE as a local therapy treatment option for controlling disease in men on active surveillance: only 4/10 treated men demonstrated negative biopsies at 6 months; however, no pathologic upgrades were found during the study period. We ¹⁶ published our experience in 21 patients evaluating the oncologic safety and clinical efficacy of PAE prior to definitive RT in men with prostate cancer. The data demonstrated significant LUTS improvement and prostate volume reduction without imaging or biochemical upgrading after the PAE prior to RT and no local or biochemical recurrence during the follow up period (average follow up of 7 months). Additionally, the data demonstrated no ≥ CTCAE grade 3 GU toxicity and 1 grade 3 GI (rectal) toxicity that healed without issue.

Several conclusions can be drawn from the limited data published to date: (1) PAE is safe in men with prostate cancer, (2) locally advanced tumor with clinical symptoms such as retention and hemorrhage can present challenging scenarios and PAE, while safe, may have moderate expectation of success, (3) LUTS improvement in men with concurrent but non-obstructive prostate cancer is similar in degree to that seen in men without prostate cancer, (4) data does not support PAE as a primary treatment modality for prostate cancer, (5) PAE results in excellent LUTS improvement and volume reduction prior to definitive RT and may allow men to be treated with hypofractionated protocols or even brachytherapy monotherapy, (6) PAE may result in reduced GI and GU toxicity after RT and (7) PAE may be an excellent option for men with post-radiation prostatitis.

Emerging Indications for PAE

Several indications exist for the utilization of PAE in men with prostate cancer (Figure 2). Overall, the indications can be split into those for men who have prostate cancer but have not had definitive therapy vs. those for men who have already been treated with definitive RT for the prostate cancer. In the former setting, depending on the indication, urinary clinical improvement and volume reduction represent important outcomes that separately and synergistically combine to improve clinical outcomes for men who undergo radiotherapy. In the latter setting, clinical improvement is the sole goal for PAE therapy.

Figure 2.

Flowchart of clinical indications for PAE Indications for PAE in the setting of prostate cancer are classified by relation to timing of definitive therapy. Prior to definitive therapy, neoadjuvant PAE for LUTS improvement or volume reduction represent particularly impactful indications. After definitive therapy, men with medically recalcitrant CP/CPPS can benefit greatly from PAE. Of note, no role has been identified for PAE prior to prostatectomy in men with prostate cancer.

Men with Prostate Cancer Prior to Definitive Radiotherapy

Active Surveillance

Men with low-risk prostate cancer treated with active surveillance can be treated similarly to men with BPH. In this scenario, and in accordance with AUA guidelines, if men have baseline moderate-severe LUTS and a large volume gland (ie, greater than 60 gm), PAE is an excellent option, particularly in medically refractory cases. The goals of PAE are to improve LUTS and urinary quality of life (QoL); specifically, LUTS improvement results in improved patient tolerability of surveillance protocol biopsies. It is important to note that after PAE, the MR characteristics of the prostate may change, particularly in the TZ. Because prostate MRIs are a critical component of active surveillance protocols for very low, low and some favorable intermediate risk prostate cancers, interpretations by fellowship trained abdominal radiologists with significant prostate MRI experience should be obtained when possible.

Definitive Surgical Therapy

Currently there is no role for PAE prior to prostatectomy. Data shows that baseline prostate volume may be correlated with increased blood loss during prostatectomy ¹⁷ however no other clinical outcomes have been shown to be impacted by baseline prostate volume. In addition, no data exists that demonstrates that baseline urinary function is correlated with post-prostatectomy clinical outcomes. Therefore, if a patient is opting for surgical prostatectomy as the definitive management of his prostate cancer, in order to minimize the number of procedures and cost, PAE should not be offered.

Prior to Focal Therapy

Currently no data exists to support the role of PAE prior to focal therapy for men with focal prostate cancer. However, an improvement in baseline urinary function prior to focal therapy might theoretically result in improved urinary functional outcomes and/or reduced likelihood of urinary function decline after focal therapy. In addition, in the setting of significant prostate volume reduction, the possibility exists that the technical aspects such as duration of the focal therapy procedure and/or time to place trans-rectal or trans-perineal probes can be improved. More data will be necessary to fully support PAE for this indication however the goals of the PAE are to reduce volume prior to focal therapy as well as to optimize urinary function prior to therapy.

Neoadjuvant PAE Prior to Definitive RT

As discussed earlier, ⁴ studies have shown that 5 years after definitive radiotherapy, up to 33% of men have been found to have grade 2 or above CTCAE GU toxicity, driven predominantly by dose to the urethra, bladder and prostate. Additionally, studies have demonstrated that men with large prostates and more severe baseline LUTS are at an increased risk of experiencing acute GU symptoms after RT. ⁵ As such, the primary goals of PAE in the neoadjuvant setting are to (1) improve LUTS and optimize urinary health prior to definitive RT and (2) reduce the volume of the gland. Both of these impacts can lead to less urinary function decline and reduced GI toxicity after RT.^18,19 It is important to recognize that men whose LUTS are primarily due to locally advanced disease may experience less significant and less durable clinical benefit from PAE and therefore expectations should be tempered in such scenarios. Men with BPH as the primary cause of LUTS with concurrent non-obstructive prostate cancer represent the most ideal patient population for PAE prior to XRT.

Several studies have demonstrated that during the interval between PAE and initiation of RT, there has been no evidence of tumor progression. Furthermore, early data shows that rates of local and biochemical recurrence are no higher than expected for men with high and very high-risk disease,^13,18 supporting the safety of PAE prior to RT. While PAE has demonstrated excellent efficacy, it is worth noting that up to 10% of men, even those with large prostates and BPH as the predominant cause of LUTS, may not experience clinical improvement, highlighting the need for better understanding of non-responder cases.^7,8 In this clinical context there, the goals of PAE are (1) LUTS improvement and optimization prior to XRT so that men can tolerate XRT with less GU toxicity and/or urinary functional decline in the post-XRT period and (2) volume reduction to allow for reduced GU/GI toxicity while also hopefully allowing an opportunity for a reduction in the number of fractions or even conversion to brachytherapy as the primary modality (see Figure 3).

Figure 3.

Example patient undergoing neoadjuvant PAE prior to XRT. 66 yo man with GGG2 prostate cancer and baseline AUA, QoL, PV of 16, 4 and 101 cc, respectively on dual medical therapy (A). 12 weeks post PAE patient’s AUA was 2 and he has been weaned off urinary medications, (B) PV 65 cc (40% reduction) patient began standard fractionation external beam radiotherapy with 7800 cGy in 39 fractions. Left transition zone is almost entirely necrosed (yellow arrow). At 1.5 years post XRT, patient has AUA 12 and QoL of 1 and remains off of urinary medications.

Men with Prostate Cancer After Definitive Radiotherapy

Post-radiation Prostatitis/Chronic Pelvic Pain Syndrome

While the National Institutes of Health classifies chronic prostatitis according to acuity and the presence of active infection, ²⁰ Type III represents the most common type and is referred to as Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS). ²¹ Pathophysiology is thought to include an inciting agent such as recurrent infection or radiation that causes prostatic damage and pelvic floor pain. For men who have CP/CPPS after radiation, treatment can be challenging and is focused on the clearance of any infection, pain control, and alleviating LUTS. ²² Clinical success of medications is variable with up to 50% of men suffering from refractory symptoms. ²² As such, the authors have previously reported on the success of PAE in men with radiation induced CP/CPPS with clinical success seen in almost 90% of patients. ¹³ While more data is necessary to confirm the efficacy of PAE in this setting, these early positive outcomes suggest that in men who have medically refractory radiation-induced CP/CPPS, PAE can be utilized with excellent safety profile and at least moderate expectation for clinical improvement. The goals of PAE in this setting are to (1) alleviate CP/CPPS symptoms to a level that allows for tolerable quality of life and (2) augment urinary medications for better efficacy in these men.

Summary

PAE is a novel therapy that has been shown to be clinically successful for men with benign BPH with resultant LUTS. In cancer patients, however, data is limited without randomized or prospective studies and suggests that men who have advanced prostate cancer with clinical symptoms (ie, LUTS or hemorrhage) will have variable levels of improvement after PAE. Therefore, management of clinical symptoms including LUTS and hemorrhage from advanced prostate cancer using PAE can be attempted safely, but should not routinely be expected to durably alleviate symptoms.

In men who have non-locally advanced prostate cancer and LUTS from BPH, several emerging indications exist and can be thought of in the setting of prior to and after definitive therapy (Figure 2). Prior to therapy, PAE may be used in the neoadjuvant setting with focal therapy or radiotherapy. PAE may also be used to alleviate LUTS in men on active surveillance. Conversely, in men who are undergoing surgical prostatectomy, PAE has no demonstrable role. After radiotherapy, PAE may be used effectively for the management of medically recalcitrant radiation induced CP/CPPS. While data in all these indications is promising, prospective studies are needed to more clearly identify men who would benefit the most from PAE.