Impacts on functional and oncological outcomes of Robotic-assisted Radical Prostatectomy 10 years after the US Preventive Service Taskforce recommendations against PSA screening
Marcio Covas Moschovas, Abdel Jaber, Shady Saikali, Marco Sandri, Seetharam Bhat, Travis Rogers, Ahmed Gamal, David Loy, Evan Patel, Sumeet Reddy, Maria Chiara Sighinolfi, Bernardo Rocco, Tadzia Harvey, Vincenzo Ficarra, Vipul Patel
AdventHealth Global Robotics Institute, USA; University of Central Florida (UCF), USA; Data Methods and Statistics, University of Brescia, Italy; ASST Santi Paolo e Carlo - La Statale University, Italy; Università degli Studi di Messina, Italy
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Vol. 50 (1): 65-79, January - February, 2024 doi: 10.1590/S1677-5538.IBJU.2023.0530
Published as Ahead of Print: December 01, 2023
ABSTRACT
Objective: In the following years after the United States Preventive Service Task Force (USP-STF) recommendation against prostate cancer screening with PSA in 2012, several authors worldwide described an increase in higher grades and aggressive prostate tumors. In this scenario, we aim to evaluate the potential impacts of USPSTF recommendations on the functional and oncological outcomes in patients undergoing robotic-assisted radical pros-tatectomy (RARP) in a referral center.
Material and Methods: We included 11396 patients who underwent RARP between 2008 and 2021. Each patient had at least a 12-month follow-up. The cohort was divided into two groups based on an inflection point in the outcomes at the end of 2012 and the beginning of 2013. The inflection point period was detected by Bayesian regression with multiple change points and regression with unknown breakpoints. We reported continuous variables as median and interquartile range (IQR) and categorical variables as absolute and relative percent frequencies.
Results: Group 1 had 4760 patients, and Group 2 had 6636 patients, with a median follow-up of 109 and 38 months, respectively. In the final pathology, Group 2 had 9.5% increase in tumor volume, 24% increase on Gleason ≥ 4+3 (ISUP 3) , and 18% increase on ≥ pT3. This translated to a 6% increase in positive surgical margins and 24% reduction in full nerve sparing in response to the worsening pathology. There was a significant decline in post-operative outcomes in Group 2, including a 12-month continence reduction of 9%, reduction in potency by 27%, and reduction of trifecta by 22%.
Conclusions: The increasing number of high-risk patients has led to worse functional and oncologic outcomes. The initial rapid rise in PSM was leveled by the move towards more partial nerve sparing. Among some historical changes in prostate cancer diagnosis and management in the period of our study, the USPSTF recommendation coincided with worse outcomes of prostate cancer treatment in a population who could benefit from PSA screening at the appropriate time.
INTRODUCTION
In May 2012, the United States Preventive Ser-vice Task Force (USPSTF) suggestions against PSA screening drastically reduced the number of patients undergoing PSA test and prostate biopsies. As conse-quence, several authors have also reported the impacts of these recommendations on prostate cancer treat-ment (1). Desai and colleagues described a population-based cohort study including 836,282 patients with PCa collected from 2004 to 2018 showing an increase in the incidence of metastatic PCa coinciding temporally with the USPSTF recommendations against PSA screening (2). Similarly, previous studies performed in other cen-ters also detected the same trends highlighting the sig-nificant impairment also in the pathology characteristics of treated cancers while comparing outcomes of RARP before and after 2012 (3-5). Obviously, stage migration due to USPSTF suggestions against PSA screening could impact on the characteristics of the treated can-cers and could influence treatment related outcomes.
With the evidence described above, consider-ing other historical changes in prostate cancer diagno-sis and management through the years, our objective is to analyze the functional and oncologic trends in pros-tate cancer outcomes ten years after the USPSTF rec-ommendations against PSA screening in patients un-dergoing robotic-assisted radical prostatectomy (RARP) in a high-volume referral center.
DISCUSSION
Our study clearly showed that USPSTF rec-ommendations against PSA screening impacted negatively on pathological characteristics of pa-tients who underwent RARP after 2012. As conse-quence, functional outcomes showed a significant impairment mainly due to the reduction of the nerve-sparing procedures. Notably, we identified a deflec-tion point with changes in the results at the end of 2012 and 2013 illustrated by a trend change analysis (logit scale) coinciding with the USPSTF recom-mendations against PSA screening in 2012. After this period, we experienced a historical reduction in PSA use on prostate cancer screening by primary doctors and urologists, which was reflected in a significantly increased rate of Gleason 7 or higher, pT3, pT4, and positive surgical margins (PSM). In our experience, we modified our surgical technique to minimize positive surgical margins to address the higher demand for high-risk and invasive tumors while maintaining oncological principles. Conse-quently, we have seen a reduction in functional out-comes, especially potency recovery, due to a wider dissection needed by these tumors.
When comparing both periods, we detected an 9.5% increase in the median tumor volume re-ported by the pathology. Therefore, due to the larger tumor burden, we had a significant reduction (24%) in patients undergoing full nerve-sparing with in-creasing rates of partial nerve-sparing. In this sce-nario, with more aggressive cancers seen daily in our practice, we described almost 30% reduction in potency outcomes in this group of patients. Simi-larly, the higher grade and stages at diagnosis were also described in several studies and by Desai and colleagues in a chronological trend analysis after evaluating the Surveillance, Epidemiology, and End Results (SEER) database with more than 830,000 pa-tients (2, 23, 24). Even though we have modified our technique to approach more aggressive tumors, our positive surgical margins (PSM) increased by 6% in patients with pT3 and pT4 stages, while in pT2 con-tinued stable. In this period, the 12-month continence rates were also reduced (by 9%).
Despite the higher demand for aggressive and invasive tumors in our practice, we could main-tain our biochemical recurrence percentages con-stant through the years. We believe that the modi-fications of our technique to approach these tumors were crucial to maintaining optimal outcomes (12). In our series, we reported BCR in patients with at least five years of follow-up, and curve ends in 2018 to avoid misleading impressions of reduced rates of BCR after this period, which is related to the short-term follow-up and not due to oncological outcomes.
Another factor we believe that may influence the increasing rates of high-grade tumors in the last years is the increasing use of active surveillance (AS) performed in the community with non-standard protocols and follow-up. We recently described our experience comparing patients who underwent RARP at the time of the diagnosis with patients re-ferred to operate in our center after undergoing ac-tive surveillance in the community (25). Comparing two groups of 181 patients, matched with a propen-sity score analysis, we found 16% higher positive surgical margins rates (38% vs. 22%, p=0.001) and a significant increase in biochemical recurrence after surveillance and delayed RARP (HR 4.0; 95%CI 1.4-12; p=0.013). In this study, our main consideration is that we are receiving numerous patients undergoing AS in non-academic centers with non-standard pro-tocols of precise AS indication, follow-up, and treat-ment plans. Furthermore, we also should consider that in 2013 the group of Johns Hopkins Hospital de-scribed a modification in the pathological report and classifications, which consists of five Grade Groups based on the Gleason score (26). In this scenario, the new classification improved the detection rates of clinically significant cancers, and it is challeng-ing to describe the potential impacts of these modi-fications in the increasing rates of high-risk prostate cancer in our center.
Being a referral center for prostate cancer considered another confounding factor of increasing rates of aggressive tumors during the period of our study should also be considered. With the growing robotic surgery experience and dissemination, most surgeons in the community have been operating low-grade tumors while referring high-risk and chal-lenging cases to these referral centers. In addition, it is important to mention that, for the same reason, there has been a shift through the years in high-risk prostate cancer treatment and management with decreasing rates of radiation therapy and increas-ing surgical indications by experienced surgeons (27, 28). Radical prostatectomy benefits in high-risk pros-tate cancer are still debatable, but several retrospec-tive studies have described potential benefits. Recent Randomized Controlled Trials are currently recruiting patients to address these possible questions (29, 30).
The main reason for the USPSTF recom-mendations against PSA regards the higher rates of overdiagnosis and overtreatment described in some studies, which could potentially benefit patients with low-grade diseases (31, 32). According to their statement (Grade D recommendation), the harms of screening prostate cancer outweigh the benefits. In this scenario, their proposal was quickly incorporat-ed into the urologic clinical practice, and the impacts can be seen in our center and numerous studies per-formed after that period. The benefits of early pros-tate cancer detection have been established in the literature for the last 30 years, and PSA screening is a crucial part of this armamentarium. Studies report-ing outcomes of prostate cancer screening showed significant reductions in metastasis and mortality before 2012, while studies like ours reported subopti-mal oncological outcomes after this period (5, 31-35).
Furthermore, the pillars of these recommen-dations were the studies performed by Gohagan et al. and Draisma et al., reporting survival rates and pos-sible overtreatment in patients screened for prostate cancer (36-38). However, in a recent reevaluation of these patients, de Vos II and colleagues reported the long-term results (21 years later) of PSA screening showing that after 10 to 12 years, the impacts of these recommendations are evident and patients with 55 to 69 years old from the non-screening group had worse outcomes with higher rates of metastasis and prostate cancer-specific mortality (39).
In the past years, the expansion of focal ther-apy (FT) also contributed to the increasing rates of high-risk prostate cancer. Some authors described that approximately one-third of these patients un-dergoing FT would present recurrence and usually have more aggressive tumors (40). However, in our study, we did not include patients undergoing Sal-vage prostatectomy due to several confounding fac-tors associated with FT, such as type of energy used, FT indication protocol, gland extension (Focal, Hemi, or Whole gland), follow-up routine, and salvage inter-vention triggers in cases of recurrence (41). Finally, we also should consider the expansion of fusion bi-opsy as a crucial factor in increasing the detection rates of clinically significant and aggressive cancers. However, this technique has been performed in the last 15 years in a few centers and, despite the im-proved detection rates, most biopsies in the commu-nity are still performed with transrectal ultrasound (TRUS) without fusion (40, 42).
Finally, with the growing body of evidence showing increasing rates of prostate metastasis and aggressive tumors due to lack or reduced applica-tions of prostate cancer screening with PSA (2), we believe that our study is crucial to alert urologists and healthcare community to keep using digital rec-tal exam (DRE) and PSA as the standard option of prostate cancer screening, especially in countries re-lying on public health with restricted access to MRI exams and genetic tests.
Despite its strengths, our study is not devoid of limitations, mainly due to the retrospective de-sign and all its inherent risks of bias. We reported a single-center experience with cases done by high-volume surgeons, and despite the comparison group and a trend analysis coinciding with the USPSTF recommendations, surgical outcomes are multifac-torial, and it is challenging to establish an exclusive causal factor for these outcomes’ modifications. We also should consider numerous historical changes in prostate cancer diagnosis and management that could influence the increasing rates of aggressive cancers. In addition, the USPSTF reviewed their rec-ommendation and slightly modified it from category D to category C, adding a “sharing decision” in their statement, which also is challenging to measure the impacts on patient care since that year (43). How-ever, to the best of our knowledge, this is one of the largest cohorts reported by a single center compar-ing outcomes of patients who underwent RARP ten years after the USPSTF recommendations. Therefore, with the data presented in our study and previous ar-ticles in the literature, we believe that PSA screening has crucial impacts on functional and oncological re-sults, and urologists and primary care doctors should maintain the screening with PSA and DRE in order to optimize outcomes in patients with prostate cancer.
CONCLUSION
In the past years, we have witnessed a sig-nificant change in the types of patients we treat and the outcomes we are able to deliver. We are seeing younger patients with higher-grade diseases, and the increasing number of high-risk patients has led to worse functional and oncologic outcomes. The initial rapid rise in PSM was leveled by the move towards more partial nerve sparing. Among some historical changes in prostate cancer diagnosis and manage-ment in the period of our study, as described in re-cent populational studies, the USPSTF recommen-dation coincided with worse outcomes of prostate cancer treatment in a population who could benefit from PSA screening at the appropriate time.
the above is an excerpt, please see the full paper for all the details: (click here to download full article)