Dov Kadmon, MD, presented “Locally Advanced Prostate Cancer” during the 24th Annual Innovations in Urologic Practice on September 13, 2019 in Santa Fe, New Mexico.

How to cite: Kadmon, Dov. “Locally Advanced Prostate Cancer” September 13, 2019. Accessed Nov 2024. https://dev.grandroundsinurology.com/locally-advanced-prostate-cancer/

Locally Advanced Prostate Cancer – Summary:

Dov Kadmon, MD, defines locally advanced prostate cancer and the basic principles of managing this group of patients on the basis of multiple urologic and oncologic societies’ guidelines. He discusses the current standard of care, as well as ongoing research into the addition of systemic therapies for these patients.

Abstract:

Prostate cancer is expected to be newly diagnosed in over 174,000 patients in the United States in 2019. The majority (up to 90%) of these cases are expected to be localized at presentation. Nevertheless, 10-15% of these patients will present with locally advanced/high-risk disease. It is important to keep in mind that while 50% of patients ultimately succumbing to prostate cancer present with metastatic disease, the locally advanced group is responsible for the majority of remaining prostate cancer deaths. It is in this group that an effective treatment strategy will have the most impact.

The strict definition of “locally advanced” is cT3-cT4 disease. A more liberal definition includes localized but high-risk disease (PSA more than 20ng/mL, Gleason 8-10, cT2c).

A review of the guidelines the European Association of Urology (EAU), the National Comprehensive Cancer Network (NCCN), and the American Urological Association (AUA)/American Society for Radiation Oncology (ASTRO) demonstrates a basic principle for managing this group of patients: Combination therapy is favored over single modality treatment. 

There is a general consensus that if radiation therapy is given as primary treatment, it should always be given jointly with androgen deprivation therapy (ADT). This is now considered the standard of care and is based on numerous high-quality publications starting with Bolla’s landmark paper 17 years ago (see Bolla M et al, 2002).

There is also a consensus that ADT, by itself, represents insufficient therapy for the majority of patients (unless they have a limited life expectancy). 

There is an additional consensus that surgery (radical prostatectomy) has an important role in these patients and is recommended by all three guidelines. Furthermore, an extended pelvic lymphadenectomy is recommended as an integral part of the operation.

Finally, from the guidelines, a recent recommendation from the AUA/ASTRO strongly endorses combining ADT with salvage radiation therapy post radical prostatectomy.

There are many retrospective studies supporting the combination of radical prostatectomy and radiation therapy in locally advanced disease. The premise in these studies is that each one of these modalities is utilized as “salvage therapy” in case the first treatment failed to achieve local tumor control. In terms of selecting the sequence, surgery is becoming the initial treatment of choice (see Zelefsky MJ et al, 2010).

Unfortunately, studies have failed to show any long-term benefit for adjuvant/neoadjuvant ADT in combination with surgery, namely, radical prostatectomy. The same can be said for Taxol-based chemotherapy so far.

Efforts to combine the “next generation” hormone therapy (enzalutamide, abiraterone) with surgery or radiation therapy are ongoing and may bear fruit in the future. Incorporation of novel biomarkers to aid in the selection of patients for the different modalities is also ongoing.

About the 24th Annual Innovations in Urologic Practice

Innovations in Urologic Practice (Innovations) is an annual, multi-day, CME-accredited conference devoted to innovative diagnostic and treatment strategies for and controversies related to some of the most common urologic problems in the current era. The topics covered include oncological management of the bladder, kidney, and prostate. The conference also emphasizes general urology topics in pelvic reconstruction and trauma, men’s health, and infections in the urology patient. Dr. Kadmon presented this lecture during the 24th Innovations in 2019. Please visit this page in order to register for future Innovations meetings.