Locally advanced prostate cancer is defined as disease extending beyond the prostatic capsule (clinical stage T3-T4), or with regional lymph node involvement (cN+), but without distant metastases (M0).
Diagnostic workup for locally advanced disease includes imaging to exclude distant metastases: bone scan, CT or MRI of abdomen/pelvis. and laboratory assessment of PSA.
Modern imaging modalities with PSMA PET are increasingly used for more accurate staging, though conventional imaging remains standard.
Primary treatment modalities center on local control and systemic therapy.
The standard of care for most patients is external beam radiotherapy (EBRT) combined with long-term androgen deprivation therapy (ADT), typically for 2–3 years.
EBRT is delivered to the prostate and seminal vesicles, with or without pelvic lymph nodes, using advanced techniques of intensity-modulated radiotherapy to minimize toxicity.
Dose escalation and the addition of a brachytherapy boost may improve biochemical control in select high-risk cases, though with increased grade 3 toxicity.
Radical prostatectomy with extended pelvic lymph node dissection is an option for select, fit patients, often as part of a multimodal strategy.
Surgery may be followed by adjuvant or salvage radiotherapy and/or ADT, depending on pathological findings (e.g., positive margins, extracapsular extension, nodal involvement).
Disease-specific survival after prostatectomy is similar for pT2 and pT3-4 tumors when multimodal therapy is applied.
ADT is used in neoadjuvant, concurrent, and adjuvant settings with radiotherapy, with long-term ADT (2–3 years) providing superior outcomes compared to short-term.
In patients with regional lymph node involvement or very high-risk features, androgen receptor pathway inhibitors (ARPIs) (e.g., abiraterone) may be added to ADT, especially in those meeting criteria such as PSA ≥40 ng/mL, T3/T4 stage, or Gleason grade 4/5.
Meta-analyses demonstrate improved metastasis-free survival with this approach.
Data support triplet therapy (ADT + ARPI + docetaxel) in select subgroups, though long-term toxicity must be considered.
Combining local (surgery or radiotherapy) and systemic therapies is associated with improved survival and disease control.
EBRT is associated with bowel toxicity, while prostatectomy more commonly results in urinary and sexual dysfunction.
Locally advanced prostate cancer is treated with a multimodal approach, most commonly EBRT plus long-term ADT, with consideration of surgery, brachytherapy boost, and systemic intensification (ARPIs, docetaxel) in select patients, tailored to disease risk and patient factors.