5.2 Radical Prostatectomy & Radiation Therapy

5.2 Radical Prostatectomy & Radiation Therapy

Definitive local therapy with curative intent forms the cornerstone of management for patients with localized and locally advanced prostate cancer who have a life expectancy greater than 10 years. The two primary therapeutic modalities—Radical Prostatectomy (RP) and External Beam Radiation Therapy (EBRT)—are established options in appropriately selected disease. Direct randomized evidence is limited, particularly for high-risk/locally advanced cancer, so equal survival across all risk categories is not established. Clinical decision-making considers tumor risk stratification, baseline lower urinary tract symptoms, baseline erectile function, patient comorbidity profiles, and patient preferences regarding treatment-related adverse effects.

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1. Radical Prostatectomy: Surgical Approaches & Anatomy

Radical prostatectomy entails the en-bloc excision of the entire prostate gland, both seminal vesicles, and ampullae of the vasa deferentia, followed by construction of a watertight vesicourethral anastomosis. The operation can be performed via open retropubic, pure laparoscopic, or robot-assisted radical prostatectomy (RARP). RARP is widely used and offers superior visualization via 3D magnification, reduced intraoperative blood loss, lower transfusion rates, and shorter hospital stays, though long-term oncological and functional outcomes are comparable when performed by high-volume surgeons.

Critical Anatomical Steps of RARP

1. Development of the Retzius Space & Endopelvic Fascia: Medial umbilical ligaments and urachus are divided to mobilize the peritoneum and bladder. In the conventional anterior approach, the endopelvic fascia is opened lateral to the prostate and levator fibres are swept away, with the dissection adapted to the intended nerve-sparing plane.
2. Dorsal Venous Complex (DVC / Santorini's Plexus) Control: The puboprostatic ligaments are identified and preserved or selectively incised. The Santorini venous plexus overlying the prostate apex is suture-ligated or divided cold with selective bipolar coagulation to avoid thermal injury to the underlying apical rhabdosphincter and cavernous nerves.
3. Bladder Neck Dissection: The anterior bladder neck is identified by palpating the inflated catheter balloon. Bladder neck preservation or minimal incision is favored in organ-confined disease to enhance early urinary continence recovery. The posterior bladder neck is transected to expose the anterior surfaces of the ampullae and seminal vesicles.
4. Seminal Vesicle Mobilization & Denonvilliers' Fascia: The vasa are clipped and divided, enabling anterior traction on the seminal vesicles. The seminal vesicles are mobilized cleanly while avoiding aggressive thermal cautery at their tips, where the pelvic plexus and inferior hypogastric nerves pass in close proximity. Denonvilliers' fascia is incised sharply to enter the retroprostatic prerectal avascular plane, safely separating the prostate from the anterior rectal wall.
5. Lateral Pedicle Division & Neurovascular Bundle (NVB) Sparing: The lateral prostatic pedicles are controlled with vascular clips rather than electrosurgical energy to prevent heat dispersion to the cavernous nerves. Dissection planes along the prostate capsule dictate functional preservation:
   • Intrafascial: Dissection directly on the true prostatic capsule, preserving all layers of the periprostatic fascia and maximum neural tissue. Indicated for low-risk, non-palpable tumors far from the capsule.
   • Interfascial: Dissection between the prostatic fascia and the lateral pelvic/levator fascia, preserving the posterolateral NVB. Select the plane according to side-specific extracapsular-extension risk rather than risk-group label alone.
   • Extrafascial (Wide Resection): Dissection outside the periprostatic fascia sacrifices the adjacent NVB where a wider oncological margin is needed, particularly with suspected EPE on that side. Capsular contact alone does not mandate bundle sacrifice; use MRI, examination and biopsy findings together.
6. Apical Dissection & Urethral Transection: Dissection at the apex requires extreme precision. The cavernous nerves lie close to the posterolateral apical urethra. Maximizing functional urethral length and preserving the external striated rhabdosphincter are critical to early postoperative urinary continence.
7. Vesicourethral Anastomosis: A continuous anastomosis may use a double-armed running suture (Van Velthoven technique) or a barbed-suture adaptation. Posterior musculofascial reconstruction (Rocco stitch) can support the anastomosis.

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2. Extended Pelvic Lymph Node Dissection (ePLND)

Pelvic lymph node dissection provides definitive pathological staging (pN0 vs pN1) and informs postoperative adjuvant or salvage strategies.

Indications & Nomogram Thresholds

• Omission in Low-Risk Disease: In low-risk prostate cancer, the incidence of lymph node metastases is <1%; PLND can be safely omitted.
• Risk Nomograms: In intermediate- and high-risk disease, validated nomograms—primarily the Briganti nomograms (2012, 2017, 2019) or the Memorial Sloan Kettering Cancer Center (MSKCC) nomogram—are employed.
• Decision Threshold: Apply a validated model to the population and biopsy method for which it was developed. Historical thresholds include 5%, while 7% was evaluated for Briganti2019; these are model-specific trade-offs, not a universal mandatory interval. Discuss occult-node detection against lymphocele/other morbidity and uncertain therapeutic benefit. If PLND is performed, use an extended template.

Anatomical Template of ePLND

Limited obturator sampling has lower nodal yield and staging sensitivity than an extended template. ePLND improves staging; a consistent survival benefit from PLND itself has not been established. The standard template includes:

• External Iliac Packet: Nodes overlying the external iliac artery and vein. Protect the vessels and adjacent genitofemoral nerve.
• Obturator Packet: Nodes cranial and caudal to the obturator nerve within the obturator fossa; preserve the nerve and recognize adjacent vessels.
• Internal Iliac (Hypogastric) Packet: Nodes medial and lateral to the internal iliac artery, an important prostatic drainage region.
• Super-extended PLND expands the template to include the common iliac nodes up to the aortic bifurcation and presacral nodes, though it carries higher rates of lymphocele formation and nerve injury.

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3. External Beam Radiation Therapy (EBRT)

Modern radiotherapy leverages advanced technologies—such as Intensity-Modulated Radiation Therapy (IMRT), Volumetric Modulated Arc Therapy (VMAT), and Image-Guided Radiation Therapy (IGRT)—to deliver dose-escalated radiation to the prostate while shielding adjacent radiosensitive organs at risk (rectum, bladder, femoral heads, penile bulb).

Dose Escalation & Fractionation Schedules

• Conventional Fractionation: Multiple prospective randomized trials (e.g., GETUG 06, MRC RT01) confirmed that dose escalation to 74–80 Gy (at 1.8–2.0 Gy per fraction) significantly improves biochemical recurrence-free survival compared to conventional doses of 64–70 Gy.
• Moderate Hypofractionation: Delivers slightly higher fraction sizes over a shorter total timeframe (e.g., 60 Gy in 20 fractions of 3.0 Gy, or 70 Gy in 28 fractions of 2.5 Gy over approximately six weeks). The CHHiP and PROFIT trials demonstrated non-inferior oncological control and equivalent late toxicity compared to 74–78 Gy conventional fractionation, making moderate hypofractionation the prevailing standard across many European healthcare systems.
• Ultra-Hypofractionation / SBRT: Established schedules include 36.25 Gy in five fractions (PACE-B; 40 Gy to the prostate target) and 42.7 Gy in seven fractions (HYPO-RT-PC). These are distinct trial regimens. EAU permits ultra-hypofractionation for selected favourable intermediate-risk disease with good urinary function and appropriate image guidance; PACE-B excluded Gleason4+3 and used no ADT.

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4. Androgen Deprivation Therapy (ADT) Combined with EBRT

ADT improves outcomes with EBRT in appropriate risk groups through local radiosensitization and systemic suppression of occult disease. Its indication and duration depend on risk, radiation regimen, comorbidity and patient preference.

Risk-Adapted ADT Regimens

• Intermediate Risk: Conventional or moderately hypofractionated EBRT is generally combined with 4–6 months ADT. Selected favourable intermediate-risk patients may omit ADT after discussion; EAU does not require ADT with its selected GG2 ultra-hypofractionation pathway. EORTC22991 improved event-free and disease-free survival with six months of concomitant/adjuvant suppression, but its long-term intermediate-risk analysis did not show statistically significant overall-survival improvement.
• High Risk / Locally Advanced: Current EAU recommends 2–3 years ADT with high-risk EBRT, with at least two years for locally advanced disease. EORTC22961 found six months inferior to three years. The five-year DART01/05 results supported longer treatment particularly for high-risk patients, but does not establish one universal optimum of 24–30 months.
• Systemic Intensification: Offer two years of abiraterone with glucocorticoid alongside RT and long-term ADT for conventionally staged cN0M0 with ≥2 factors: cT3–4, Gleason≥8, PSA≥40 ng/mL, and for cN1M0. This is the STAMPEDE-supported EAU recommendation, distinct from treating every high-risk patient identically.
• Pelvic Nodal Irradiation: For cN0 disease, elective whole-pelvis irradiation is individualized; high risk or a Roach estimate alone does not mandate it. The Roach estimate is $[2/3 \times \text{PSA}] + [(\text{Gleason}-6) \times 10]$ percent. In selected trials, pelvic treatment around 46–50 Gy improved disease-control endpoints but increased toxicity; a universal benefit is unproven. cN1M0 treatment includes prostate and pelvis RT with long-term ADT and abiraterone.

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5. Prostate Brachytherapy

Brachytherapy achieves intense localized radiation delivery with rapid dose fall-off, sparing adjacent normal tissues.

• Low-Dose Rate (LDR): Permanent ultrasound-guided transperineal seeds, usually iodine-125 (half-life approximately 60 days) or palladium-103 (17 days). Monotherapy is reserved for appropriately selected favourable disease; EAU specifically recommends it for NCCN-favourable intermediate risk with good urinary function. Assess symptoms and flow (commonly IPSS <12, Qmax >15 mL/s), gland geometry and pubic-arch access. Volume above 50–60 mL is a technical consideration rather than an absolute exclusion. Prior TURP is not an automatic contraindication: adequate residual tissue, healing and careful urethral dosimetry are essential; EAU advises at least three months after TURP.
• High-Dose Rate (HDR) Boost: Temporary catheters deliver iridium-192 radiation, then the source is removed. One- or multiple-fraction boost schedules are combined with EBRT, commonly ≥45 Gy, plus risk-appropriate ADT. LDR boosts are another option. Both can improve biochemical control in unfavourable intermediate/high-risk disease, with additional urinary toxicity requiring counselling.

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6. Treatment Selection Algorithm by Risk Category

EAU2026 grouping below uses PSA/Grade Group with DRE-based clinical stage. Some brachytherapy recommendations explicitly use NCCN favourable/unfavourable categories; these are not interchangeable with EAU definitions.