Importance: Biochemical recurrence (BCR) following radical prostatectomy (RP) is an unreliable predictor of distant metastatic progression or prostate cancer death, consequently resulting in overtreatment. Following BCR, guidelines recommend that patients are treated with radiation therapy. However, little has been published about observation without secondary treatment management recommendations.

Objectives: Establish that a cohort of patients can be managed with observation without secondary intervention, and establish a process to safely manage men with BCR using observation versus therapeutic secondary intervention following RP using kinetics of PSA doubling time (PSAdt).

Methods: In a retrospective cohort analysis of 1865 patients following RP from June 2002 and September 2019 at a tertiary referral center, 407 patients experienced BCR as defined as two PSA levels >0.2ng/ml. 137 were managed with observation compared to 270 treated with secondary intervention. Using PSAdt graphs, patient doubling times (DT) kinetics were (re)calculated with each new date and PSA level and categorized as Increasing or Decreasing. Kaplan-Meier analysis and multivariate logistic regression were used to model PCSM and no need for treatment, respectively.

Results: Table 1 describes the patient Demographics between the Observation and Treatment groups. Significant univariate differences include preoperative PSA, pathologic stage (p-stage), pathological Gleason Grade Group (pGGG), and DT change. The median follow-up was 7.3 years (IQR 3.9-10.7). 10-year Kaplan-Meier analysis demonstrated no PCSM in the observation group compared to 7.1% PCSM in the treated group (p=0.001).In adjusted logistic regression analysis, PSAdt > 12 months and increasing DT were significant predictors for continued observation without treatment (p<0.001), while pGGG was p=0.06. In ROC analysis, the model including these three variables were an excellent predictor of no need for treatment (AUC = 0.84), similar to the model including only PSAdt and pGGG (AUC = 0.82). In adjusted logistic regression analysis in patients with PSAdt < 12 months, PSAdt group 6-12 months and increasing DT were significant predictors of no treatment. Of interest, pGGG was not predictive of treatment.

Conclusions and Relevance: There exists a group of patients (137/407, 33%) who can be observed without secondary treatment following BCR after RP, with 0% PCSM. No patients with PSAdt > 12 months experienced PCSM. PSAdt > 12 months, increasing DT, and a low pGGG (1-2) were excellent predictors of no need for treatment. Further studies of DT kinetics in cohorts of patients with PSAdt < 12 months in subset analysis may help direct more tailored processes for timing and intensity of treatment.

Introduction: Androgen deprivation therapy (ADT) or radiation therapy (RT) with ADT is frequently recommended for biochemical recurrence (BCR) following a radical prostatectomy (RP). Probably the most severe life-threatening complication of ADT is an adverse cardiovascular event (ACE) such as acute myocardial infarction, stroke, etc. Because the literature is conflicted as to whether ADT increase ACEs. This study seeks to assess relationship of ACE in men undergoing ADT following RP.Methods: Retrospective review of prospectively collected data (n = 1895) from patients who underwent robot-assisted radical prostatectomy (RARP) performed by a single surgeon. 308 patients with a biochemical recurrence (BCR) and adequate follow-up data were analyzed for ACE. 189 men in the “treatment group” (TG) were managed with ADT or RT/ADT. The comparator group consisted of 119 men undergoing active observation (AO) with BCR but received no ADT or RT/ADT. Differences between AO and TG were analyzed utilizing student t-test and chi-squared (Table 1). Logistic regression was used to find predictors of ACE. Kaplan-Meier survival curves were generated to find time to ACE event and the percentage of patients that did not have an event. Results: At baseline, time of surgery, there was no significant difference in Charlson comorbidity index (CCI) but there was a trend in favor of AO (4.14 versus 4.38). In follow-up following BCR significant predictors of ACE in univariate analysis were age, CCI, body mass index (BMI), treatment status (AO vs TG), and smoking status (non-smoker vs previous smoker). 15-year Kaplan-Meier (KM) analysis showed a statistically significant increase in ACEs (TG 54.4% and AO 41.8%, p = 0.02). The driving factors for the increase in ACEs was coronary artery disease and arrhythmia. In the TG, there were no differences in ACE between ADT versus RT+ADT (55.4% versus 53.8%, p = 0.68). In adjusted multivariate logistic regression analysis, CCI and BMI were significant predictors for ACE with treatment status trending toward significance. Conclusions: There is an association between treatment for BCR and subsequent cardiovascular morbidity (as measured by ACE). Treatment may not undoubtedly cause ACE but that it may carry a higher risk of ACE. This effect may be attributed to time, or increasing the risk of particular types of ACE, but not to other types of ACE. We also saw the importance of BMI and CCI as a prognosticating tool for ACE, over treatment status.

Objective: To introduce a patient-reported percent erection fullness scale (% fullness) following robot-assisted radical prostatectomy (RARP) as a qualitative adjunct to the International Index of Erectile Function - 5 (IIEF-5) questionnaire and as a 90-day predictor of two-year potency outcomes.

Patients and Methods: Prospective data was collected from 540 men with normal preoperative sexual function (defined as an IIEF-5 score between 22 and 25) who underwent RARP by a single surgeon, of which 299 had complete data at all follow-up time points. In addition to standard assessment tools (IIEF-5 and erections sufficient for intercourse), patients were asked to “indicate the fullness you are able to achieve in erections compared to before surgery?” (0-10...100%). The primary outcome was prediction of potency (defined as ESI) at 24 months, based on 90-day % fullness tertiles (0-24%, 25-74%, and 75-100%).

Results: 299 men with complete follow-up were included in initial analysis. Significant predictors of 24 month potency included age, BMI, pathologic stage, nerve-sparing status, and % fullness tertiles. In multivariable analysis, % fullness demonstrated excellent prediction of 2-year potency recovery (R2=0.89) and internal validation suggests good discrimination (AUC = 0.83). Repeated analysis in the full patient cohort (n=540) yielded similar results.

Conclusions: We introduce % fullness as a qualitative adjunct to the IIEF-5 and as a 90-day predictor of two-year potency recovery post-RP. This initial report is hypothesis-generating such that the use of % fullness enables the identification of men most likely to benefit from early, secondary intervention.

The relationship between testosterone and prostate cancer is both complex and understudied. Impact of testosterone on disease aggressiveness, overall health status, and sexual function are of particular interest in both prostate cancer patients and in aging men. As such, the present study seeks to explore the impact of free testosterone on sexual function in prostate cancer patients (PCa) undergoing radical prostatectomy.

From 2009 to 2019, 783 men with localized PCa were treated with robot-assisted radical prostatectomy (RARP). Total testosterone and sex hormone binding globuin (SHBG) was collected from all patients and free testosterone (cFT) was prospectively calculated. Sensitivity analysis was performed to identify relevant cut-points in age, free testosterone, and sexual function scores. Impact of free testosterone (cFT), age, comorbidity status, and disease characteristics were considered as covariates and linear regression models were generated to predict sexual function.

In sensitivity analysis, men over the age of 60 had significantly lower cFT, higher serum prostate specific antigen (PSA) and prostate weight. Additionally, these men also had a higher proportion with high-risk (GGG 9-10) and high-volume (p-stage T3/T4) disease. After adjusting covariates in linear regression, cFT was an independent predictor of preoperative IIEF-5 scores for men above the age of 60 years (p=0.001, Beta: 0.140, 95% CI: 0.165 – 0.690). In addition, prostate weight was a significant covariate of preoperative IIEF-5 scores for men above 60 years of age (p=0.013, Beta: -0.110, 95% CI: -0.066 – -0.008). cFT appears to be an independent predictor of preoperative sexual function in older men with PCa.

These results highlight the deleterious effects of long-term exposure to low cFT. We emphasize that cFT (over total testosterone) should be systematically checked in all men regardless of age. Furthermore, testosterone replacement therapy should be considered as an early intervention strategy in at-risk patients.

Objective: To analyze the oncological outcomes of “at-risk” men with Prostate cancer (PC) following radical prostatectomy who were managed without versus with adjuvant radiation therapy (ART). Additionally a cost comparison will be conducted between radiotherapy and observation groups.

Patients and Methods: 1500 men who underwent robot-assisted radical prostatectomy (RP) and no adjuvant radiation therapy at UC Irvine constitute the comparator group, (Observation group) of men who had a RP for prostate cancer and managed without ART. Observation patients with no PSA follow-up or who had pre-operative treatment were excluded. All data was prospectively collected and retrospectively analyzed in the observation group. Two comparator groups of men who received ART were selected from two randomized control trials (SWOG 8794 and EORTC 22911) and separately analyzed against the UCI observation group. Outcomes assessed in the analysis include Biochemical recurrence (BCR), metastasis-free survival, prostate cancer specific mortality (PCSM) and Overall survival. Kaplan-Meier analysis was utilized to compare outcomes with previous randomized control trials. Medicare reimbursement rates were used to estimate cost of secondary interventions.

Results: 364 patients were selected by SWOG 8794 inclusion criteria. After adjusting by proportion of Gleason score and pathological stage, the UCI observation cohort had non-inferior outcomes with metastasis-free and overall survival rate than the trial. Also, analysis in 368 men who were qualified by EORTC 22911 inclusion criteria demonstrated the similar non-inferior results in overall survival and cancer-specific survival rate. Cost per patient in the RCTs was $26,343 for ART groups and $7,874 in the RCT control groups after considering primary, secondary complication treatment expenses versus UCI only $3,544 per patient.

Conclusion: Radiation-naïve patients had non-inferior oncological outcomes as compared to men receiving ART. The expense of ART is three to seven times higher than radiation-naïve men. Decision of early radiation treatment should be re-evaluated because of the lack of mortality benefit, side effects of radiotherapy and cost.

Importance: Prostate cancer remains as one of the most common malignancies in men in the United States. A substantial portion of men experience a biochemical recurrence (BCR) following radical prostatectomy (RP). Salvage surgeries, such as pelvic lymph node dissection (sPLND) and pelvic mass resection (sPMR) are utilized as potential interventions in eligible patients with BCR. However, the factors that predict success of salvage surgeries remain largely unknown.

Objectives: This study aims to investigate the utility of Prostate-specific Antigen doubling time (PSADT) kinetics in predicting salvage surgery success, defined as no need for further treatment post-salvage surgery. In patients who failed and required subsequent treatment, we aim to assess the utility of multiple dimensions of PSA kinetics in predicting the time to treatment post-salvage surgery.

Methods: A retrospective analysis of data from 32 patients with BCR post-RP who underwent salvage surgery was conducted. PSADT graphs were constructed for each patient to represent the pre- and post-salvage periods. A smoothing algorithm was applied to the data to refine PSADT calculation and analysis. The primary independent variable was the average PSADT rate of change over the one-year period pre-salvage surgery. The secondary variables included the instantaneous PSADT rate pre-salvage, pre-salvage PSADT, pre-salvage PSA, and post-salvage PSADT rate. The cohort was stratified into two groups: salvage surgery success (N=12) and salvage surgery failure (N=20). Two-tailed independent t-tests, chi-squared analyses, and linear regression analyses were utilized to compare and analyze our data.

Results: There were no statistically significant differences between the salvage surgery success and failure groups (Table 1-2). Additionally, none of the univariate or multivariate linear regression models were able to identify statistically significant predictors of salvage surgery success in our primary analysis. Subset analysis of the failure group also failed to identify any significant predictors of time to post-salvage surgery treatment.

Conclusion and Relevance: The study did not yield significant predictors of salvage surgery success or time to post-salvage surgery treatment, within the context of PSADT kinetics. This speaks to the complexity and challenges associated with using PSA kinetics alone in predicting salvage surgery outcomes. Additionally, this study highlights the need for studies with larger cohorts that integrate advanced analytical tools to create more refined predictive models. Future studies exploring the general applicability of quantified PSADT rates in post-RP treatment decision-making are warranted.