Optimal management of prostate cancer with lethal biology - state-of-the-art local therapy

Abstract

Defining prostate cancer with lethal biology based upon clinical criteria is challenging. Locally advanced/High-Grade prostate cancer can be downstaged or even downgraded with cure in up to 60% of patients with primary therapy.12345 However, what is known is that high-grade prostate cancers have a greater potential for recurrence and progression to metastatic disease, which can ultimately result in a patient's death. Patients with clinical features of “high-risk” prostate cancer (cT2c, PSA >20, ≥ Gl 8 on biopsy) are more likely to harbor more aggressive pathologic findings. The optimal management of high-risk prostate cancer is not known as there are not prospective studies comparing surgery to radiation therapy (RT). Retrospective and population-based studies are subject to many biases and attempts to compare surgery and radiation have demonstrated mixed results. Some show equivalent survival outcomes6 while others showing an advantage of surgery over RT.7891011 Local therapy for high-risk disease does appear to be beneficial. Improved outcomes realized with local therapy have been clearly demonstrated by several prospective studies evaluating androgen deprivation therapy (ADT) alone versus ADT plus RT. The combination of local with systemic treatment showed improved disease-specific and overall survival outcomes.121314 Unfortunately, primary ADT for N0M0 prostate cancer is still inappropriately applied in general practice.11 While the surgical literature is largely retrospective, it too demonstrates that surgery in the setting of high-risk prostate cancer is effective in providing durable disease-specific and overall survivals.2315

Molecular mechanisms underlying resistance to androgen deprivation therapy in prostate cancer

“…Ultimately, the decision between surgery and radiation for initial therapy lies with the patient and the expertise of his urologic oncology team [ 34 ]. Lastly, ADT can also be used in this population as a monotherapy, termed primary ADT (Table 1 ); however, the multimodal approaches described above are favored for high-risk patients without distant metastases [ 24 , 26 , 29 , 36 ].…”