FOCAL THERAPY Anterior Gland Ablation as a Novel Treatment for Magnetic Resonance Imaging–detected Clinically Significant Anterior Prostate Cancer

By: Kae Jack Tay, MBBS, FAMS (Urology), Singapore General Hospital; Denis Seguier, MD, Centre Hospitalier Régional Universitaire de Lille, France; Jonathan Oliver, MD, PhD, Centre Hospitalier Régional Universitaire de Lille, France; Arnauld Villers, MD, PhD, Centre Hospitalier Régional Universitaire de Lille, France | Posted on: 09 Jun 2023

Anterior Prostate Cancer

Energy-based partial gland ablation is an emerging treatment for localized intermediate-risk prostate cancer (PCa) aimed at reducing the morbidity associated with radical whole gland therapy, while providing cancer control.1 These focal therapies are adapted to PCa location, such as the peripheral zone (PZ), transitional zone (TZ), or anterior fibromuscular stroma (AFMS).2

MRI and targeted biopsies have led to better detection and localization of PCa, such as diagnosing anterior PCas (APCs) originating from the TZ.3 APCs account for 19% of new cancers.4,5 It was demonstrated that APCs originate from anterior and medial TZ as well as anterior to urethra in the midline.6 Due to benign prostatic hyperplasia enlargement, APCs then spread anteriorly into the AFMS while the anterior limit of TZ acts as a barrier to APCs extending posteriorly (Figure 1).4

Figure 1. Three types of transitional zone origin cancers. Anterior fibromuscular stroma cancers excluded from transitional zone into anterior fibromuscular stroma with benign prostatic hyperplasia growth. Reprinted with permission from Bouye et al, Prostate. 2009;69(1):105-113.5

Occasionally, an APC nodule can be located mainly within the AFMS and anterior to TZ boundary, without any cancer in the PZ. Focal or partial treatment is appealing in these highly selected cases, representing 3%-5% of new cancers. The aim is to preserve intact the posterolateral aspect of distal (submontanal) urethra, PZ and periprostatic tissues. Doing so, the tumor is ablated with a safety margin of benign tissue posteriorly, delivering superior continence/potency outcomes to radical prostatectomy (RP) while allowing pathological assessment of excised tissue.

Focal Therapy or Ablative Partial Treatments for Anterior PCa

An array of ablative technologies exists that can be applied to the prostate.7 The 2 most studied technologies are cryotherapy and high-intensity focused ultrasound (HIFU). When ablation is carried out focally rather than whole-gland, men are significantly more likely to preserve their sexual function.8 Tay et al reported in a phase 2 clinical trial that when ablation occurred next to a neurovascular bundle, recovery of sexual function was delayed by about 6 months.9 APCs, being situated far away from the cavernosal nerve bundles, thus are ideal for focal therapy as they can be completely ablated without impacting erectile function.

Sze et al demonstrated the feasibility of treating APCs with image-guided focal cryoablation with minimal deterioration in International Prostate Symptom Score and International Index of Erectile Function over 15 months and negative post-procedural biopsies in 17 men.10 Notably, cryoablation is a transperineally directed treatment approach. This allows the active tips of the cryotherapy needles to be placed directly into the anterior prostate without passing through or damaging structures collateral to the posterior prostate/PZ. While there are no published data, these advantages should theoretically apply to other newer transperineally delivered focal therapy modalities such as irreversible electroporation, where an electrical current causes pore formation in the cell membrane and subsequent apoptosis, or laser ablation, where thermal energy is deposited with high precision.

In contrast, the transrectal approach employed with HIFU disadvantages it in the treatment of APCs. First, the ultrasound energy deployed must be of a sufficiently high level in order to traverse the posterior zone and reach an APC. This may increase the risk of thermal damage to the rectum and PZ and to the urethra leading to fibrosis and stricture. Second, prostatic swelling as the treatment is ongoing may result in anteriorly shifting the target zone, inadvertently sparing tissue between the stacked treatment sectors. Huber et al showed that men who underwent anterior focal HIFU were nearly twice as likely to require retreatment compared to those who underwent posterior focal HIFU.11

The differential advantages of transperineal and transrectal approaches have led some to suggest that choosing an approach is best done “à la carte” and individualized to the patient’s tumor location.2 On the horizon, HIFU can now be deployed transurethrally as an in-bore MRI-guided treatment.12 This may improve the ability of HIFU to completely ablate APCs. However, the capital cost of this approach is high, and it is not yet widely available.

Partial Prostatectomy for Anterior PCa

Where the APC is apical, however, the delivery of thermal energy may be undesirable, for fear of compromising the external sphincteric unit and/or the neurovascular bundles.2 In this specific circumstance, en bloc surgical excision of the anterior prostate (ie, TZ, AFMS, anterior part of PZ) was evaluated.

Partial prostatectomy has been described as an alternative to focal ablation therapy for the management of localized low- to intermediate-risk PCa. It consists in robotic assisted anterior partial prostatectomy (APP) for anteriorly located tumors entirely or partially within the AFMS (Figures 2 and 3). Initial report of robotic APP showed good functional results and acceptable oncological results.13,14 Long-term outcomes in an extended series of 28 men (2000-2022) confirmed these results (Villers, unpublished data). The median follow-up was 7 years (IQR 4.2-8). Median PSA pre-APP was 9.6 (6-11). Continence remained uninterrupted in 92% of patients. Erectile function without drug remained uninterrupted in 69%. Median nadir PSA post APP was 0.36 ng/mL (IQR:0.25-0.60). Cancer recurrence, diagnosed due to PSA rise by biopsies at the margins of the primary cancer resected area, was observed in 8 patients and led to salvage completion robotic radical prostatectomy at a median time of 3.25 years (IQR:2.4-6). Freedom from post-APP cancer recurrence was 62.7% (35.0-81.3). No patients had systemic treatment or metastases.

Figure 2. Case 25 (PSA 5.8 ng/mL; prostate volume 96 cc). Isolated anterior 1.1-cc grade group (GG) 2 lesion suspicious at MRI in the anterior fibromuscular stroma on the midline (arrows). A, MRI transverse T2. B, MRI transverse dynamic contrast-enhanced sequence. C, MRI transverse apparent diffusion contrast map. D, MRI T2 parasagittal view. Inclusion criteria comprised an MRI-targeted biopsy-proven predominant anterior prostate cancer (APC) based on MRI findings, ie, at a distance of at least 17 mm (biopsy core length) from rectal surface, with negative posterior 12 systematic biopsy series (see Figure 1) or separate microfoci GG1 <4 mm. Exclusion criteria comprised magnetic resonance–documented APC located within 5 mm of the posterior transitional zone boundary, GG 4 or 5 (GS ≥8), clinically significant cancer outside the APC or in the peripheral zone lateral horns and previous local or systemic therapy. PSA value at baseline was not used as a selection criterion provided the cancer was localized at imaging.

Figure 3. Schematic view of the prostate. Sagittal (A) and transverse (B) at the mid gland. The red dotted line shows the dissection plane of the anterior partial prostatectomy. The average anterior prostate cancer anterior to urethra and in the anterior fibromuscular stroma (AFMS) is depicted in green. The protocol comprises en bloc template excision of the anterior part of the prostate including the AFMS, prostate adenoma (transitional zone [TZ] and median lobe) with the proximal urethra (PU), the anterior part of the distal (submontanal) urethra (DU), the most anterior apical parts of the peripheral zone (PZ), and the anterior bladder neck (BN).

Figure 4. Anterior partial prostatectomy was performed in all cases in 5 steps in the following order: retrograde dissection of peripheral zone (PZ) and transitional zone (TZ) at the apex, opening of the anterior bladder neck (BN), antegrade dissection of TZ lobes at posterior bladder neck, lateral sectioning of PZ, bladder suturing to urethra and PZ. Sagittal section of prostate, bladder, seminal vesicles, urethra, and periprostatic fascia. The average anterior prostate cancer is depicted in green. The red dotted line shows the dissection plane of the anterior partial prostatectomy. Step 1: division of dorsal venous complex (DVC; 1–arrow) and anterior half of the urethra at the apex. Step 2: retrograde division of the apex (2–arrow). Step 3: anterior BN division (3–arrow). Step 4: posterior BN and median lobe enucleation (4–arrow). AFMS indicates anterior fibromuscular stroma; BW, bladder wall; DA, detrusor apron; DU, distal urethra; FC, Foley catheter; ML, TZ median lobe; PS, pubic symphysis; PU, proximal urethra; RUM, rectourethralis muscle; RW, rectum wall; SS, striated sphincter; SV, seminal vesicles; VM, verumontanum; VEF, ventral endopelvic fascia.

In conclusion, partial gland ablation offers a promising alternative to standard treatments for localized intermediate-risk prostate cancer. By selectively targeting cancerous tissue, this approach minimizes side effects while maintaining cancer control. Further research, including larger sample sizes and longer follow-ups, is necessary to establish the inclusion criteria and long-term efficacy and safety of partial gland ablation in personalized prostate cancer management.

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