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.
Patients with regional lymph node involvement may also benefit from definitive local treatment as a retrospective study of 2967 patients with pelvic node positive prostate cancer had a survival advantage associated with local therapy of radical prostatectomy or radiation therapy, and ADT compared with ADT alone with an overall survival with five years of 78.8% versus 49.2%, respectively.
The addition of an androgen biosynthesis inhibitor abiratone is also considered in patients with regional nodal involvement: there is improved six year metastasis free survival of 82% in patients receiving abiratone and ADT versus 69% in patients receiving ADT alone, with both groups receiving local RT.
In elevation of PSA level of greater than 0.2 ng per mL is considered recurrent prostate cancer: a higher PSA threshold of nadir +2 ng per mL is used to define recurrence after radiation because normal prostate tissue may remain after RT.
Biochemical recurrence, defined as an elevated PSA as the sole indicate of recurrent disease, may occur in 20 to 40% of patients who undergo definitive therapy.
Salvage radiation to the surgical bed may be used for individuals who have undergone radical prostatectomy and experiencing biochemical recurrence.
For individuals with biopsy proven recurrent localized prostate cancer, who initially received radiation, salvage options of radical prostatectomy, cryotherapy, high intensity ultrasound may be considered.
In patients with high risk biochemical recurrence enzalutamide plus leuprolide improves metastasis free survival compared with leuprolide alone.
With PSMA PET imaging approximately 68% of patients who previously have been considered, as having a biochemical recurrence are found to have metastatic disease.