Rationale for cytoreduction – first, he accepts that cytoreductive prostatectomy is the first step of a multimodal approach, that likely includes systemic therapy and radiation. However, in completing a prostatectomy up front, the biologic rationale is that you can eliminate intraprostatic, castration-resistant potentially lethal prostate cancer cell clones that may be hiding in the primary gland. The ultimate purpose of cytoreduction is to improve progression-free and overall survival – but also to prevent local progression and associated morbidities.
Tzalepi et al. (JCO 2011) demonstrated in 32 patients with cT3aN+ PCa who underwent ADT and docetaxel following by prostatectomy that the prostate continued to harbor tumor cells that had molecular features of potentially lethal prostate cancer. The prostate may be a safe haven despite systemic therapy – and may give rise to clones for future metastases, leading to systemic recurrence.
In a SEER paper by Culp et al. (EU 2014), the authors found that who underwent local therapy (either radiation or surgery) in the setting of primary metastatic prostate cancer had lower cancer-specific mortality over a 7-8 period – favoring radical prostatectomy. However, this is naturally biased by its retrospective nature and unknown patient selection.
Dr. Heidenreich himself, along with colleagues (Heidenreich et al. JUrol 2015), presented his institutional experience with cytoreduction in a highly selected patient population with locally resectable PCa (based on mpMRI), <= 3 hot spots on bone scan, pelvic lymph node metastases allowed, but without retroperitoneal lymph nodes or visceral metastases. Patients were treated with 6 months neoadjuvant ADT, and in the men whose PSA dropped below 0.4 ng/mL, a RP and extended PLND was completed. All patients received adjuvant ADT for 2 years. The patients had 14% positive margin rate and 56% node-positive rate. These 32 patients were compared to 38 controls, and median follow-up was 40-44 months. They found that the men in the intervention arm had a clinically significant improvement in PFS, CRPC-free survival, and cancer-specific survival.
In a more recent study, they combined their data with another institution for a total of 113 patients (Heidenreich et al. EU 2018). With a mean follow-up of 53 months, 75% had low-volume skeletal metastases, while 25% had volume. Only 3% had visceral metastases, and 71% had neoadjuvant ADT. To-date, median overall survival has not yet been reached – approximately 85% survival at 96 months. Mean clinical relapse-free survival is 72.3 months – compared to 33 and 34 months in the CHAARTED and LATITUDE studies.
He briefly discussed the recent STAMPEDE data (Parker et al. Lancet 2018), specifically the recent presentation of the role of radiotherapy in the setting of metastatic prostate cancer. This very important study demonstrated that men with low-volume disease have significant failure-free and overall survival benefit with the treatment of the primary tumor. However, he noted that with radiation, even in the low volume patients, there was 28% symptomatic progression at 3 years – and it was 57% in the high-volume patients. This is where radical prostatectomy may improve on radiotherapy.
He concluded with the following slide that summarizes his opinion on the matter and the data that exists so far:
However, we as a surgical community, need to do a better job of keeping up with surgical clinical trials to demonstrate with high-quality data what we believe to be true. Hopefully, trials that are currently recruiting can help better address this question for us!
Presented by: Axel Heidenreich, Professor of Urology, Chairman, and Director of the Department of Urology, Uro-Oncology, Robot-Assisted, and Specialized Urologic Surgery at the University Hospital in Cologne Germany
Written by: Thenappan Chandrasekar, MD. Clinical Instructor, Thomas Jefferson University, Twitter: @tchandra_uromd, @TjuUrology, at the 16th Meeting of the European Section of Oncological Urology, #ESOU19, January 18-20, 2019, Prague, Czech Republic