(UroToday.com) Dr. Peter Carrol began his talk stating one general thing that can still improve, and this was the reduction of disparities in care affected by ethnicity, gender, insurance and education, geographic distance, and disparities specific to the LGBTQ community. Urology can help in this matter by allowing itself to be a more diverse and welcoming specialty.
Next, Dr. Carrol moved on to discuss 4 things that he had learned in his distinguishable career about prostate cancer.
1. Prostate Cancer is a Spectrum of Disease.
It is important to build an infrastructure early in your center. Some examples of what this can include is a tissue bank, research registries and granular databases, and invest in the improvement of outcomes (patterns of care, health-related quality of life, and resource utilization).
Dr. Carrol then elaborated on the CAPRA score formulated at his institution. This is the Cancer of the Prostate Risk Assessment (UCSF-CAPRA) score. CAPRA is a straightforward 0 to 10 score. It is easy to calculate, with accuracy comparable to the best nomograms. A CAPRA score is valid across multiple treatment strategies, and it predicts an individual's likelihood of metastasis, cancer-specific mortality, and overall mortality.
The score is calculated using points assigned to:
- Age at diagnosis
- PSA at diagnosis
- Gleason score of the biopsy
- Clinical stage
- Percent of biopsy cores involved with Cancer
The Cancer-specific and overall survival using the CAPRA score are shown in Figures 1 and 2.
Figure 1 – CAPRA – Cancer-specific survival:
Figure 2- CAPRA – Overall survival:
Dr. Carrol's team tried to see if the addition of biomarkers such as Oncotype GPS can improve the CAPRA score's ability to predict pathology (figure 3). Most biomarkers used to date are prognostic. In the future, there will be significant progress in the development of biomarkers which are predictive (predicting response to treatment).
Figure 3 – Oncotype GPS and CAPRA score – predicting pathology:
Dr. Carrol emphasized the importance of basic science research and how critical it is to continue to develop this growing field of research, which is the basis for all other research.
It is also important to measure your outcomes as a surgeon and a physician. Every surgeon needs to learn from his outcomes and be able to counsel patients and collaborators honestly and transparently.
2. Detect Some, Treat Some
The screening, detection, and treatment paradigms of prostate cancer have changed drastically through the years. While once the paradigm was to detect and treat all cancers, today, the accepted paradigm is to detect and treat only some of the cancers. We need to avoid the detection of low-risk disease, and if the low risk is detected, patients should be offered surveillance and not definitive radical treatment.
There are also significant problems with PSA, the most commonly used biomarker for prostate cancer diagnosis, which includes testing outside of the target population, over-testing, limited specificity (resulting in frequent biopsies), and over-detection and overtreatment. This can be improved using various additional biomarkers, such as 4K score, in an attempt to avoid unnecessary biopsies, or multiparametric MRI, to lower the missed diagnosis rates of significant cancers (Gleason Grade 2 or above) (Figure 4).
Figure 4 -Upfront 4K score testing, followed by multiparametric MRI and biopsy at certain thresholds:
3. Who to Treat
The management strategy of active surveillance is a response to the over-detection and over-treatment of prostate cancer brought about by widespread and repeated PSA screening. Its uptake by the urology community helped pave the way for an upgraded assessment by the USPTF on the early detection of prostate cancer. There is, however, still significant variation in the utilization of active surveillance in the USA (2010-2015), as shown in figure 5.
Figure 5- Active surveillance utilization in the US 2010-2015:
When assessing the risk factors for biopsy reclassification (Gleason grade >=2) on active surveillance, it was shown that high genomic score and PSA density >=0.15 were risk factors for reclassification within 3 years of commencing active surveillance. PSA kinetics was also associated with the longer-term risk of reclassification at 5 and 10 years.
Pattern 4 subtype of the Gleason score has many histopathologic features that are apparent but not typically reported. These include the expansive, poorly formed, and fused subtypes (Figure 6). Cribriform histology and stromal reaction are associated with higher genomic scores and a higher risk of extracapsular extension and recurrence, compared to glomerulation and no stromal reaction. Therefore, even if the amount of Gleason score 4 is low, not every Gleason score 4 is a candidate for active surveillance, especially if it harbors these aggressive subtypes.
Figure 6 – Gleason grade 4 subtypes:
Active surveillance protocol is quite burdensome, and it would be very beneficial if we could make the protocol more "user-friendly," as suggested in figure 7.
Figure 7 – How to make active surveillance protocol less burdensome:
Although we have overtreated low-risk disease, we have also undertreated high-risk prostate cancer. Radical prostatectomy has come a long way, and it significantly changed in the last decades. While once it was reserved for low-risk patients with low-grade disease, with over-treatment being common and the survival benefit being limited, nowadays, it has become most beneficial for high-risk patients, with the usage of other advanced features such as biomarkers, novel imaging and implementing a multimodal approach.
4. Imaging Will be Critical
With a negative predictive value of 85-90%, the introduction of multiparametric MRI has assisted in deciding who to biopsy and has improved our method of biopsying. It is currently used in conjunction with other biomarkers to decide whether to biopsy or not. However, we lack more sensitive imaging modalities, as we are still constricted by the limited sensitivity of standard imaging in those with the high-risk disease at diagnosis. Additionally, at the time of biochemical recurrence, treatment decisions are rarely based on clear evidence of the site of recurrence.
PSMA-PET imaging is a fast-growing novel imaging modality used in advanced prostate cancer patients. It has been shown to have impressive sensitivity and specificity at relatively low PSA values (Figure 8). However, we still lack data on whether it changes outcomes, whether it is cost-effective, who should be imaged and when, and whether theranostics (imaging and treating) is recommended.
Figure 8 – PET PSMA at biochemical recurrence:
Summarizing his talk, Dr. Carrol reiterated that it is important to build infrastructure early on, seek opportunity and not convenience, and be prepared to think and act differently than expected. It is vital to continue and build teams of great people with diversity in mind, in and outside of Urology, as the best investment is, and will always remain, in human capital.
Presented by: Peter Carrol, MD, MPH, Professor, Department of Urology, Ken and Donna Derr-Chevron Distinguished Professorship in Urology, Taube Family Distinguished Professor in Urology Department of Urology, UCSF, San-Francisco, California, USA
Written by: Hanan Goldberg, MD, MSc., Urology Department, SUNY Upstate Medical University, Syracuse, NY, USA, @GoldbergHanan at the Virtual 2020 EAU Annual Meeting #EAU20, July 17-19, 2020.