Advanced Locally Invasive Prostate Cancer with High-Risk Features

Introduction to High-Risk Prostate Cancer

The European Association of Urology recommends that a 3.8 cm lesion with multiple zones of the prostate involved indicates a substantial tumor burden 1, 2, 3, 4.
The American Urological Association states that a PI-RADS 5 lesion has a >95% probability of clinically significant cancer requiring treatment 1, 2, 5.

The National Comprehensive Cancer Network (NCCN) classifies patients with T3a or higher stage disease as high-risk, regardless of PSA or Gleason score 6.
High-risk patients with seminal vesicle involvement have a 27-58% risk of disease progression depending on additional risk factors 6.

The NCCN recommends definitive radiation therapy combined with long-term androgen deprivation therapy (24-36 months) for high-risk prostate cancer 6, 7.
The European Society for Radiotherapy and Oncology suggests high-dose external beam radiation (78-80+ Gy) using image-guided techniques targeting the prostate, proximal 2.0-2.5 cm of seminal vesicles, and potentially pelvic lymph nodes 6, 7.

The NCCN recommends urologic oncology consultation within 1-2 weeks to discuss treatment options and staging completion 6.
The American College of Radiology suggests a complete staging workup for high-risk disease, including CT chest/abdomen/pelvis, bone scan, and consideration of PSMA PET/CT if available 6, 8, 5.

The Mayo Clinic states that without treatment, high-risk prostate cancer represents life-threatening disease with a high probability of progression to metastatic cancer 9.
The NCCN reports that with appropriate multimodal therapy, long-term disease control is achievable in the majority of patients who complete the full treatment course 6.

Extraprostatic invasion of the neurovascular bundle indicates locally advanced prostate cancer that confers a significantly worse prognosis, with approximately 70-75% of patients developing biochemical recurrence within 3-4 years despite surgical resection, and represents high-risk disease requiring multimodal treatment rather than surgery alone 10
Extraprostatic extension is an independent prognostic factor that predicts worse outcomes, similar in impact to seminal vesicle involvement and positive surgical margins 10

Positive surgical margins increase the rate of recurrence by 2- to 4-fold and are independently predictive of prognosis 10

Renal ultrasound and CT scan should be performed for patients with stage T3 cancer 11, 12
Pelvic lymphadenectomy should be performed if surgical treatment is pursued, as lymph node involvement is common and virtually all men with nodal disease experience progression 10
Bone scan is indicated given the locally advanced nature of disease 11, 12