ESOU18: Reappraisal of Neoadjuvant Therapy for High and Very High-risk Prostate Cancer - Yes

Amsterdam, The Netherlands ( It is known that 20-35% of prostate cancer (PC) patients present with high risk disease, and 15-40% have lymph node involvement. Furthermore, 40-65% of patients experience biochemical recurrence (BCR) within 5 years of local treatment. Lastly, prostate cancer specific mortality (CSM) is almost 20% at 15 years.

Current European Association (EAU), National Comprehensive Cancer Network (NCCN), and American Urologic Association (AUA) guidelines do not recommend hormonal therapy before radical prostatectomy (RP), even for high risk disease. Additionally, for high risk disease the EAU guidelines recommend RP, if the tumor volume is low. There is a growing interest in performing surgery for high risk locally advanced and oligometastatic PC. Moreover, the EAU guidelines recommend surgery for high risk disease with high tumor volume, as part of a multimodal treatment strategy.

According to Dr. Volpe, neoadjuvant therapy in high risk locally advanced PC is appropriate due to several reasons:

  1. Provides earlier systemic therapy for micro-metastatic disease
  2. Can achieve cytoreduction, enabling the resection to be slightly easier
  3. Enables us to assess the effect of treatment agents on the final surgical specimen
  4. Has the potential to assess in vivo surrogate biomarkers of treatment response
Factors not supporting the administration of neoadjuvant therapy include:

  1. Causes delay in surgery
  2. Represent an overtreatment in a proportion of patients
  3. Leads to treatment related complications
Several randomized trials exploring neoadjuvant hormonal therapy prior to RP in high risk patients failed to demonstrate an improvement in survival outcomes, although it did demonstrate a reduction of positive surgical margins and increased organ confined disease rate. In contrast, according to the EAU guidelines, combining hormonal therapy for 2-3 years with radiotherapy
(RT) for high risk localized PC patients is recommended. Furthermore, in patients with lymph node involvement, it is prudent to offer pelvic external radiation in combination with long term hormonal therapy. Hormonal therapy decreases prostate volume, leading to a lower RT dose that is required to treat the tumor, and reduces the volume of healthy tissue exposed to RT. Additionally, hormonal therapy increases the oxygenation of PC cells, thereby making the PC cells more sensitive to RT. Hormonal therapy induces apoptosis of cancer cells, producing micro-metastasis. Lastly, hormonal therapy induces apoptosis of PC cells and potentially eliminates cell clones which could be resistant to RT.

Chemotherapy (CHEM) is effective in advanced metastatic PC. There are several multi-phase trials demonstrating the safety of neoadjuvant CHEM before RP. However, there is lack of evidence demonstrating improved clinical outcomes.

There are currently 50 ongoing phase 1 and 2 trials assessing neoadjuvant targeted therapies and immunotherapy. The potential targets under investigation in these trials include the VEGF receptor, the epidermal growth factor receptor (EGFR), the platelet derived growth factor receptor (PDGFR), clusterin, and various immunotherapeutic targets.

In summary, neoadjuvant hormonal therapy before RP does not impact survival outcomes. Hormonal therapy combined with RT is recommended in high risk disease. Neoadjuvant CHEM before RP is safe and feasible in phase 2 trials and might be associated with a better prognosis. Results of phase 3 trials are awaited to clarify the role of CHEM in this setting. Proper patient selection remains the key factor.

Speaker: Alessandro Volpe, MD University of Eastern Piedmont Hospital, Maggiore Della Carita Hospital, Novara, Italy

Written By: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre @GoldbergHanan at The 15th Meeting of the EAU Section of Oncological Urology ESOU18 - January 26-28, 2018 - Amsterdam, The Netherlands