Large study challenges long-held views on Gleason 10 PCa

“Journal Article of the Month” is a new Urology Times section in which Badar M. Mian, MD (left), offers perspective on noteworthy research in the peer-reviewed literature.  Dr. Mian is associate professor of surgery in the division of urology at Albany Medical College, Albany, NY.

Over the last 10 years, low-risk prostate cancer has garnered significant attention and the focus has been on identifying strategies to avoid overtreatment. The opposite end of the prostate cancer spectrum has received less attention. A recent report by Sandler et al aims to provide some insights into  the treatment-related outcomes in our highest risk prostate cancer patients (ie, biopsy Gleason score 10) (Int J Radiat Oncol Biol Phys 2018; 101:883-8). The authors point out that over 50% of these patients can remain free of systemic disease for 5 years after treatment with a combination of modalities.

Also by Dr. Mian: mpMRI Bx protocol may reduce repeat biopsies, but at what cost?

Biopsy Gleason score 10 is uncommon and in the more recent Gleason grouping system, both Gleason scores 9 and 10 are combined into group 5. The authors combined data from 12 different centers to identify 112 patients with biopsy Gleason score 10 over the last 13 years. These patients had been treated with either radical prostatectomy (RP), external beam radiation therapy (EBRT), or external beam radiation therapy plus brachytherapy boost (EBRT-BT). In addition, androgen deprivation therapy for nearly 2 years was used in 98% of patients undergoing EBRT and in 79% undergoing EBRT-BT. In the RP group, 35% had received neoadjuvant systemic therapy and 34% received postoperative EBRT.

Due to the lack of uniformity in defining biochemical recurrence, the authors focused on the clinical outcomes following prostate cancer treatment such as overall survival (OS), prostate cancer-specific survival (PCSS), and distant metastasis-free survival (DMFS).

After a median follow-up of 4.9 years, no differences were noted among various treatment groups in terms of OS or PCSS. The 5-year OS rates in the RP, EBRT, and EBRT-BT groups were 80%, 73%, and 83%, respectively, while the 5-year PCSS rates were 87%, 75%, and 94%, respectively. The EBRT-BT group appeared to have some statistical advantage over EBRT in terms of DMFS (87% vs. 62%), but there was no difference when compared to the RP group (64%).

Next: Nearly 2/3 can remain free of metastatic disease

Nearly two-thirds can remain free of metastatic disease

These data highlight the fact that regardless of the treatment combination, nearly two-thirds of these high-risk patients can remain free of metastatic disease. This is in contradistinction to the long-held and often presented view that patients with Gleason score 10 prostate cancer may already have metastases and that primary treatment may not be necessary.

Read: Negative Bx during AS linked with lower risk of reclassification

It is important to point out that the patients in this report were likely detected through a screening process and thus may have somewhat lower volume of disease compared to the historical controls, as evident from the fact that median PSA level was less than 10 ng/mL and 67% of patients had clinical stage T1 or T2. The authors correctly point out some of the weaknesses of the study, which are often unavoidable when retrospectively pulling data from different centers, such as heterogeneity and lack of central pathology review. Other information, such as quality of life following various combinations of treatment, would have been quite informative.

While these results cannot be extrapolated to men with very high PSA level or advanced clinical stage, the study provides appropriate benchmark data for our contemporary patients with high-risk clinically localized prostate cancer. Unlike the historical approach to Gleason score 10 prostate cancer management, it appears that aggressive, multimodality combination therapy can result in significantly long metastasis-free (and treatment-free) intervals.