e17144 Background: There are varying definitions of high-risk prostate cancer. The most commonly used is the NCCN definition which defines patients as having high- or very-high-risk disease if they have any of clinical T3 or greater disease, Gleason Grade Group 4 or 5, or PSA > 20ng/mL. Recent studies of androgen receptor signaling inhibitors have employed alternative definitions of baseline risk. Herein, we compared patient distributions and oncologic outcomes for patients undergoing radical prostatectomy according to two definitions of high-risk disease. Methods: Using an institutional database of patients undergoing radical prostatectomy, we characterized patients as having high-risk disease either by using NCCN risk groups (any of Gleason grade group [GGG] 4 or 5; or Clinical T3 or T4; or PSA >20 ng/mL) or using the definition employed in the PROTEUS trial (overall GGG ≥3 and at least one of the following: GGG5 in at least one core; or GGG4 in at least 2 cores, each with >80% involvement; or GGG3+ in ≥6 systematic cores; or GGG3+ in ≥3 systematic cores and PSA ≥20 ng/mL). Descriptive statistics were used to compare patient distributions. Area under the receiver operating curve (AUC) were compared between NCCN- and PROTEUS-based definitions of high-risk disease for oncologic outcomes including extra-prostatic extension, positive surgical margins, and PSA >0.1 or >0.2 at 12 months post-operatively. Results: Among 424 patients undergoing radical prostatectomy in the dataset, 358 had complete pathological biopsy data allowing for nuanced pre-operative risk stratification. Of these, 62 (17%) were classified as high-risk per NCCN criteria while 44 (12%) were classified as high-risk per PROTEUS criteria. Among 62 patients classified as high-risk per NCCN criteria, 38 met the PROTEUS criteria and 24 did not. Conversely, among 44 patients classified as high-risk per PROTEUS criteria, 38 met the NCCN high-risk criteria and 6 did not. Using AUC, the two definitions were comparably predictive of extra-prostatic extension (NCCN 0.56, 95% CI 0.52-0.60; PROTEUS 0.56, 95% CI 0.53-0.60; p=0.96), positive surgical margins (NCCN 0.54, 95% CI 0.49-0.58; PROTEUS 0.52, 95% CI 0.49-0.56; p=0.44), PSA >0.1 at 12 months post-operatively (NCCN 0.54, 95% CI 0.46-0.62; PROTEUS 0.59, 95% CI 0.51-0.67; p=0.22), and PSA >0.2 at 12 months post-operatively (NCCN 0.59, 95% CI 0.49-0.69; PROTEUS 0.64, 95% CI 0.54-0.75; P=0.32). Conclusions: This comparative analysis based on highly granular data shows that prostate cancer patients defined as high-risk based on NCCN risk groups, or high-risk criteria employed in the PROTEUS clinical trial, have comparable outcomes. Therefore, identifying patients suitable for treatment intensification with peri-operative systemic therapy is critical in this evolving clinical landscape.

BackgroundAndrogen-deprivation therapy (ADT) remains a cornerstone in treatment for patients with advanced prostate cancer. ADT is associated with several adverse effects, including osteoporosis, metabolic syndrome, and cardiovascular events, leading to guidelines recommending routine testing to monitor for these toxicities. There is a lack of data assessing adherence to these recommendations.MethodsThe authors conducted a retrospective cohort study using administrative data from Ontario, Canada between 2008 and 2021. They identified all older men (aged 65 years and older) who received ADT for prostate cancer using comprehensive provincial health databases. The primary outcomes were the use of testing for lipids, dysglycemia (glucose), bone health serum, and bone density between 6 weeks before and 1 year after the initiation of ADT.ResultsIn total, 29,097 patients were examined, of whom 52.8% were prescribed ADT by urologists, 37.9% were prescribed ADT by radiation oncologists, 2.8% were prescribed ADT by medical oncologists, and 2.4% were prescribed ADT by other physicians. Adherence to guidelines was low: only 21.3% of patients received a bone density scan, 41.2% underwent bone health-related serum tests, 51.3% completed a lipid profile, and 65.9% underwent dysglycemia testing within 1 year of diagnosis. Overall, only 11.9% of patients received all of the recommended investigations. Adherence to testing did not appear to improve over time (2008-2021) or with guideline publication. Patient (age) and physician (specialty) factors had important associations with adherence to testing.ConclusionsMost patients receiving ADT for prostate cancer do not receive recommended testing to monitor for treatment-related toxicity. Further study is required to address barriers to therapeutic monitoring of men on ADT and to reduce treatment-associated adverse events. Androgen-deprivation therapy (ADT) remains a cornerstone in treatment for patients with advanced prostate cancer and is associated with several adverse effects. Population-based assessment revealed that only 11.9% of patients on ADT received all of the recommended testing to screen for adverse effects associated with ADT.

INTRODUCTION:Treatment intensification with androgen receptor signaling inhibitors and/or chemotherapy is guideline recommended for patients with de novo metastatic hormone-sensitive prostate cancer (mHSPC). However, most patients only receive androgen deprivation therapy monotherapy. The aim was to identify physician-, patient-, and tumor-related factors associated with the receipt of treatment intensification. METHODS:A population-based cohort study was conducted in Ontario, Canada, which included men ≥66 years newly diagnosed with de novo mHSPC between January 2014 and December 2022. Hierarchical regression modeling was used to examine the association of physician, patient, and tumor characteristics with the receipt of treatment intensification, defined as the initiation of an androgen receptor signaling inhibitor, docetaxel, or both within six months of diagnosis. Darlington's method was used to assess predictor importance via standardized regression coefficients (SRC). RESULTS:Among 6099 eligible older men newly diagnosed with de novo mHSPC, 1475 (24.2%) received treatment intensification. In multivariable modeling, patients initiated on androgen deprivation therapy by radiation oncologists were less likely to receive treatment intensification (odds ratio [OR]. 0.48; 95% CI, 0.37-0.61; p < .01; SRC: 19.46; p < .01) whereas those by medical oncologists were more likely to receive treatment intensification (OR, 1.64; 95% CI, 1.21-2.22; p < .01; SRC: 9.56; p < .01), each compared to urologists. Older patients were significantly less likely to receive treatment intensification (OR 0.94 per year over age 66; 95% CI, 0.93-0.95; p < .01; SRC: -36.21; p < .01). CONCLUSION:Patient and physician characteristics significantly influence variation in the use of treatment intensification for de novo mHSPC. These findings inform targeted interventions and policies to enhance the delivery of life-prolonging mHSPC care.

96 Background: Intensified treatment beyond androgen deprivation therapy (ADT) has been shown to improve survival in patients with metastatic castrate-sensitive prostate cancer (mCSPC). However, real-world utilization remains inadequate. To assess potential differential access to such life-prolonging treatments, we assessed the association between sociodemographic marginalization and receipt of intensified treatment in patients newly diagnosed with mCSPC within a universal healthcare system. Methods: We performed a population-based cohort study of men aged 66 years or older diagnosed with de novo mCSPC in Ontario, Canada from Jan 2014-Nov 2021. Hierarchical regression models adjusting for patient, tumor, and physician characteristics were used to estimate odds ratios (OR) and 95% confidence intervals (CI) for the association between patient marginalization, measured by the Ontario Marginalization Index (ON-MARG), and receipt of intensified treatment, within 6 months of diagnosis. ON-MARG, a validated measure created using Canadian census data, provides area-level measures of marginalization in four domains: (1) households and dwellings; (2) material resources; (3) age and labour force; and (4) racialized and newcomer populations. Results: Among 6,051 patients, 1,465 (24%) received intensified treatment. Higher levels of composite marginalization were associated with a lower likelihood of receiving intensified treatment (OR 0.91, 95% CI 0.83–0.99, p=0.03). When examining individual domains of marginalization (Table 1), the racialized and newcomer populations domain showed the strongest negative association with the receipt of intensified treatment (OR 0.89, 95% CI 0.81–0.97, p=0.01). Conclusions: Sociodemographic marginalization, particularly among racialized and newcomer populations, is associated with lower rates of intensified treatment in patients with de novo mCSPC, even within a universal healthcare system, further contributing to known disparities in prostate cancer outcomes. Association between ON-MARG domains and treatment intensification among patients with de novo mCSPC in adjusted models.* ON-MARG Domain Effect Estimate (95% CI) Households & Dwellings OR 0.92 (0.85-0.98), p=0.02 Material Resources OR 0.93, (0.86-0.99), p=0.03 Age & Labour Force OR 0.99, (0.94-1.04), p=0.65 Racialized & Newcomer Populations OR 0.89, (0.81-0.97), p=0.01 *Each ON-MARG Domain was modelled in separate multivariable models adjusting for patient characteristics including age at diagnosis, Charlson comorbidity category, and area; tumor characteristics including Gleason score at diagnosis; as well as physician age, sex, years in practice, specialty, and group volume.

69 Background: Treatment intensification using androgen receptor signaling inhibitors (ARSIs) or chemotherapy is guideline-recommended for patients with mCSPC based on improved survival and preserved quality of life. However, numerous studies across jurisdictions have shown relatively limited uptake, with most patients receiving androgen deprivation therapy (ADT) monotherapy. Therefore, we sought to understand patient, physician, and tumor characteristics associated with treatment intensification. Methods: This population-based cohort study in Ontario, Canada included older men (age ≥66 years) diagnosed with de novo mCSPC between Jan 2014 and Nov 2021 for whom the ADT-prescribing physician could be identified (>99.5% of all mCSPC patients). We used hierarchical regression modelling to assess the association (presented as odds ratio, OR) between patient sociodemographic characteristics and comorbidities, tumor characteristics, and physician characteristics with receipt of intensified treatment for mCSPC, defined as receipt of an ARSI, docetaxel, or both within 6mo. We used Darlington’s method to assess the relative importance of these predictors (presented as standardized regression coefficients, SRC). Results: Among 4450 eligible older men newly diagnosed with de novo mCSPC, 18.8% received treatment intensification, with rates increasing from 6.3% in 2014 to 31.9% by 2021. In multivariable modeling, patient age was the most influential variable, with older patients significantly less likely to receive treatment intensification (SRC -43.8, OR 0.91, 95% CI 0.90-0.92). Socioeconomic status (SRC -12.2; OR 0.54, 95% CI 0.33-0.88 for quintile 1 vs 5) and a history of stroke (SRC -11.5, OR 0.28, 95% CI 0.09-0.86), but no other patient factors including comorbidity, were significantly associated with intensification. Patients prescribed ADT for mCSPC by radiation oncologists were less likely to receive intensification (SRC -16.5; OR 0.47, 95% CI 0.23-0.95) compared to other providers without significant differences between patients treated by urologists, medical oncologists, or other physicians. No other physician-level characteristic (age, sex, years in practice, or annual volume of prostate cancer patients) was associated with treatment intensification. More contemporary year of diagnosis was also strongly predictive (mean SRC 31.2) of intensification. We noted significant geographic variation (mean SRC 10.2; p<0.0001), that could not be explained by rurality (p=0.08) and persisted after adjustment for socioeconomic status and patient characteristics. Conclusions: Patient, disease, and physician characteristics contribute to variation in treatment intensification for mCSPC. These data may allow focused intervention to improve guideline-concordant care for patients with mCSPC.

OBJECTIVE:The COVID-19 pandemic resulted in decreased prostate specific antigen (PSA) testing for prostate cancer screening and its impact remains uncharacterized. Our objective was to compare incident PSA testing rates, PSA levels, and prostate cancer treatment rates before and during the pandemic after the state of emergency (SoE) was declared. MATERIALS AND METHODS:This was a population-based, retrospective cohort study among men 50-80 years of age in Ontario, Canada undergoing incident PSA testing from November 23, 2018 to July 9, 2021. Working backwards and forwards from the date of the province-wide SoE (March 17, 2020), 30-day time periods were constructed during which incident PSA testing rates were measured. Our primary outcome was the rate of incident PSA testing. Secondary endpoints included comparison of incident PSA levels and prostate cancer treatment rates. RESULTS:We identified 835,402 men who underwent incident PSA testing. There was a 20% decrease in PSA testing after the SoE (RR = 0.80,95% CI: 0.800.81, P < .001). There was a higher proportion of extreme PSA levels after the SoE with a higher proportion of patients with a PSA >20 ng/mL (rate ratio = 1.63,95% CI: 1.54-1.73, P < .0001) and >100 ng/mL (rate ratio = 1.98,95% CI: 1.77-2.20, P < .0001). This effect was highest for those aged 50-59 years. More patients required active treatment (5,201,59.5% prior to the pandemic vs. 5,072,64.2%, P < .001 after the SoE declaration). CONCLUSIONS:The COVID-19 SoE resulted in patients experiencing a 2-fold increase in the risk of having an extreme PSA level and higher odds of treatment. Future studies are needed to assess the impact on the rates of advanced prostate cancer and cancer-specific mortality.

You have accessJournal of UrologyProstate Cancer: Detection & Screening VI (MP74), Moderated Poster 741 May 2024MP74-09 THE PREVALENCE OF EXTREME SERUM PROSTATE SPECIFIC ANTIGEN LEVELS DURING THE COVID-19 PANDEMIC Amanda E. Hird, Rano Matta, Refik Saskin, Erind Dvorani, Sarah Neu, Sender Herschorn, and Robert K. Nam Amanda E. HirdAmanda E. Hird , Rano MattaRano Matta , Refik SaskinRefik Saskin , Erind DvoraniErind Dvorani , Sarah NeuSarah Neu , Sender HerschornSender Herschorn , and Robert K. NamRobert K. Nam View All Author Informationhttps://doi.org/10.1097/01.JU.0001008632.59099.b9.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The COVID-19 pandemic resulted in decreased prostate specific antigen (PSA) testing for prostate cancer screening and its impact remains uncharacterized. Our objective was to compare incident PSA testing rates, PSA levels, and prostate cancer treatment rates before and during the pandemic after the state of emergency (SoE) was declared. METHODS: This was a population-based, retrospective cohort study among men 50-80 years of age in Ontario, Canada undergoing incident PSA testing from November 23, 2018 until July 9, 2021. The period of the province-wide SoE was declared on March 17, 2020 due to the rise of COVID-19 infection rates. Working backwards and forwards from this date, 30-day time periods were constructed, beginning November 23, 2018 and ending July 9, 2021 during which incident PSA testing rates were measured. Our primary outcome was the rate of incident PSA testing before and after the SoE declaration. Secondary endpoints included comparison of incident PSA levels and prostate cancer treatment rates. RESULTS: We identified 835,402 men who underwent incident PSA testing. There was a 20% decrease in PSA testing during the pandemic (RR=0.80, 95%CI: 0.80-0.81, p<0.001), compared to before. There was a higher proportion of extreme PSA levels after the SoE with a higher proportion of patients with a PSA greater than 20 ng/mL (rate ratio=1.63 95%CI: 1.54-1.73, p<.0001) and greater than 100 ng/mL (rate ratio=1.98, 95%CI: 1.77-2.20, p<.0001), compared to before. This effect was highest for those aged 50-59 years. More patients required active treatment (5,201, 59.5% prior to the pandemic vs. 5,072, 64.2%, p<0.001 after the SoE declaration), including the use of androgen deprivation therapy alone or in combination with radiation. CONCLUSIONS: The COVID-19 SoE resulted in patients experiencing a two-fold increase in the risk of having an extreme PSA level (>100 ng/mL) and higher odds of treatment for advanced disease. This data will provide more information to decision-makers when considering future pandemic planning. Source of Funding: This study was supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health and Long–Term Care (MOHLTC). This study also received funding from the Ajmera Family Chair in Urologic Oncology awarded to RKN © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e1196 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Amanda E. Hird More articles by this author Rano Matta More articles by this author Refik Saskin More articles by this author Erind Dvorani More articles by this author Sarah Neu More articles by this author Sender Herschorn More articles by this author Robert K. Nam More articles by this author Expand All Advertisement PDF downloadLoading ...

This is a summary of existing systematic reviews comparing robotic assisted radical cystectomy (RARC) with open radical cystectomy (ORC). Our aim was to compare operative approaches with respect to perioperative, postoperative, oncologic, and health-related quality of life (QOL) outcomes. We performed a systematic review of MEDLINE, Medline-in-Process and Medline Epubs Ahead of Print, and the Cochrane Library on 22 February 2022. We included reviews of adult patients with bladder cancer undergoing RARC or ORC for muscle invasive or high-risk non-muscle invasive bladder cancer. Nonrandomized studies were excluded to minimize confounding and selection bias. The GRADE approach was used to determine the confidence in estimates. We assessed the quality of identified systematic reviews using AMSTAR 2 checklist. Six well-conducted, systematic reviews and meta-analyses were included. RARC was consistently associated with lower estimated blood loss (EBL) and transfusion rates, and longer operative time. There was inconsistent evidence for the impact of RARC on hospital length of stay (LOS). There was no significant difference in overall complication rate or major complication rate, or oncologic outcomes between groups. Comparison of QOL outcomes between studies was limited by statistical and methodological heterogeneity. RARC is associated with improvement in EBL and transfusion risk. There does not appear to be differences in oncologic outcomes or complications between approaches. Prospective studies are needed to assess the impact of diversion type, technique, and recovery pathways on patient outcomes and to assess the impact of operative approach on cost and patient-reported QOL.

Introduction:Radical cystectomy and trimodal therapy are both accepted options in the management of muscle-invasive bladder cancer. As such, we sought to evaluate the micro-level costs associated with both modalities.Methods:All patients undergoing trimodal therapy or radical cystectomy for primary treatment of urothelial muscle-invasive bladder cancer at a single academic center between 2008 and 2012 were included. Direct costs associated with each phase of a patient's clinical course were collected from the hospital's financial department, and physician costs were calculated based on the provincial fee schedule. Costs of radiation treatments were derived from previously published literature.Results:A total of 137 patients were included. The mean (& PLUSMN;SD) patient age was 69 (& PLUSMN;12) years. Overall, 89 (65%) patients underwent radical cystectomy and 48 (35%) were treated with trimodal therapy. The radical cystectomy group had higher rates of cT3/T4 compared to those in the trimodal therapy group (51% vs 26%, P < .001). The median cost in the treatment phase for radical cystectomy was $30,577 (IQR: $23,908-$38,837) vs $18,979 ($17,271-$23,519) for trimodal therapy (P < .001). There was no significant difference between treatment groups with respect to cost of diagnosis or workup. However, the cost of follow-up care was numerically higher for patients undergoing trimodal therapy compared to radical cystectomy ($3,096/y vs $1,974/y, P = .09).Conclusions:In appropriately selected patients with muscle-invasive bladder cancer trimodal therapy costs are not prohibitive and are lower than in radical cystectomy. With increasing follow-up time after primary treatment, the cost difference between modalities may be mitigated by the need for bladder surveillance and salvage therapy in the trimodal therapy cohort.

Objectives Our objective was to compare prostate cancer detection rates between patients undergoing serum prostate-specific antigen (PSA) vs magnetic resonance imaging (MRI) for prostate cancer screening. Design Phase III open-label randomised controlled trial. Setting Single tertiary cancer centre in Toronto, Canada. Participants Men 50 years of age and older with no history of PSA screening for ≥3 years, a negative digital rectal exam and no prior prostate biopsy. Interventions Patients were recommended to undergo a prostate biopsy if their PSA was ≥2.6 ng/mL (PSA arm) or if they had a PIRADS score of 4 or 5 (MRI arm). Patients underwent an end-of-study PSA in the MRI arm. Primary and secondary outcome measures Adenocarcinoma on prostate biopsy. Prostate biopsy rates and the presence of clinically significant prostate cancer were also compared. Results A total of 525 patients were randomised, with 266 in the PSA arm and 248 in the MRI arm. Due to challenges with accrual and study execution during the COVID-19 pandemic, the study was terminated early. In the PSA arm, 48 patients had an abnormal PSA and 28 (58%) agreed to undergo a prostate biopsy. In the MRI arm, 25 patients had a PIRADS score of 4 or 5 and 24 (96%) agreed to undergo a biopsy. The relative risk for MRI to recommend a prostate biopsy was 0.52 (95% CI 0.33 to 0.82, p=0.005), compared with PSA. The cancer detection rate for patients in the PSA arm was 29% (8 of 28) vs 63% (15 of 24, p=0.019) in the MRI arm, with a higher proportion of clinically significant cancer detected in the MRI arm (73% vs 50%). The relative risk for detecting cancer and clinically significant with MRI compared with PSA was 1.89 (95% CI 0.82 to 4.38, p=0.14) and 2.77 (95% CI 0.89 to 8.59, p=0.07), respectively. Conclusions Prostate MRI as a stand-alone screening test reduced the rate of prostate biopsy. The number of clinically significant cancers detected was higher in the MRI arm, but this did not reach statistical significance. Due to early termination, the study was underpowered. More patients were willing to follow recommendations for prostate biopsy based on MRI results. Trial registration number NCT02799303.

65 Background: The natural history of non-metastatic castrate resistant prostate cancer (nmCRPC) prior to the introduction of novel anti-androgen agents in a real-world setting is largely unknown. Methods: This was a retrospective population-based cohort study of men with nmCRPC in Ontario, Canada. Patients with a diagnosis of prostate cancer, castrate level of testosterone ( < 1.7nmol/L) and a PSA > 2.0nmol/L with a subsequent rise > 25% from the nadir, and without diagnostic or treatment codes for metastasis were included. Annual prevalence of nmCRPC was calculated. Crude time from nmCRPC to metastasis and death are presented as medians with interquartile range (IQR). Predictors of time from nmCRPC to prostate cancer death were compared using univariable and multivariable Fine and Gray subdistributional hazard models to account for the competing risk of non-prostate cancer death. Results: From January 2007 until March 2018, we identified 2045 patients with nmCRPC. Median age was 79 years (IQR: 72-84). A total of 984 patients (48.1%) received upfront hormonal therapy while 584 (25.8%) received initial radiotherapy (RT) and 478 (23.4%) underwent radical prostatectomy. Median time from primary treatment to nmCRPC was 6 years (IQR: 3-10). PSA at the time of meeting nmCRPC criteria was a median of 3.0 ng/L. Patients were followed for a median 31.1 months (IQR: 19.8-47.9). The overall annual prevalence of nmCRPC ranged from 1,519-1,913 patients, representing 7-12% of men with prostate cancer prescribed androgen deprivation therapy each year. Crude median time from nmCRPC to all-cause death was 37.6 months (IQR: 22.1-55.4). Median time from nmCRPC to metastasis and metastasis to all-cause death was 20.0 and 8.3 months, respectively. On regression analysis, older age, ADT use with primary treatment, higher PSA at the time of meeting nmCRPC criteria, and grade group predicted time from nmCRPC to prostate cancer death. Conclusions: This is the largest analysis of the prevalence and natural history of nmCRPC. The current study can be used as a historical cohort to compare how novel imaging modalities and advancements in systemic therapy for patients with nmCRPC impact prevalence estimates and disease trajectory over time.

Introduction: Radical cystectomy (RC) is the historic gold standard treatment for muscle-invasive bladder cancer (MIBC), but trimodal therapy (TMT) has emerged as a valid therapeutic option for selected patients. Given that prospective clinical trials have been difficult to perform in this area, our aim was to compare these two primary treatment strategies using decision analytic methods. Method: A two-dimensional Markov microsimulation model was constructed using TreeAge Pro to compare RC and TMT for patients with newly diagnosed MIBC. A comprehensive literature search was used to populate model probabilities and utilities. Our primary outcome was quality-adjusted life expectancy (QALE). Secondary outcomes included crude life expectancy (LE) and bladder cancer recurrences. The simulated patient for our model was an adult with MIBC (pT2-4 N0 M0) who was a candidate for either RC or TMT. Results: A total of 500 000 patients were simulated. TMT resulted in an estimated mean QALE of 7.48 vs. 7.41 for RC. However, the average LE for patients treated with TMT was lower compared with RC (10.20 vs. 10.74 years). A sensitivity analysis evaluating the impact of age showed that younger patients treated with RC had greater QALE and longer LE than those treated with TMT; inverse findings were observed for elderly patients. Overall, 39.4% of patients treated with TMT experienced a bladder recurrence. Conclusions: RC results in a longer LE compared to TMT (0.54 years), but with a lower QALE (-0.07 years). The preferred treatment strategy varied with patient age.

239 Background: Baseline prostate specific antigen (PSA) is a strong predictor of clinically significant prostate cancer. In a large cohort of patients undergoing opportunistic testing, our objective was to assess the association between first serum PSA in combination with other PSA predictors and risk of prostate cancer. Methods: This was a retrospective, population-based study in Ontario, Canada between 2010-2019. Men 40-75 years of age who underwent incident PSA testing with at least two PSA tests during the study period were included. Among men who underwent PSA testing, the PSA levels of patients who were diagnosed with prostate cancer were compared to patients who were not. Univariable and multivariable logistic regression analysis was used to compare any prostate cancer and clinically significant prostate cancer diagnosis (International Society of Urological Pathology [ISUP] grade group 2-5) between groups. Results: A total of 508,238 patients were included in our cohort (12,444 cases and 495,794 controls). The median follow-up time was 8.2 years (IQR: 7.0-9.1). Patients who were diagnosed with prostate cancer were older (median age 62 [IQR: 56-67] versus 56 years [IQR:50-63], standardized difference [SD]:0.61) and had a higher first PSA than patients who were not (median 4.79 [IQR:3.29-6.96] versus 0.96 ng/mL [IQR:0.58-1.69], SD:1.93). Fewer than 0.1% (248/261,463) of patients with a first PSA less than 1.0 ng/mL were diagnosed with prostate cancer during the study period. Our final multivariable model revealed that a first PSA above 2.0 ng/mL (adjusted odds ratio [OR] 6.64, 95%CI: 6.13-7.20, p < 0.001), a final PSA between 4.0 to 9.9 ng/mL and 10.0 to 20.0 ng/mL (adjusted OR 22.09, 95%CI: 20.58-23.71, p < 0.001 and adjusted OR 47.46, 95%CI: 43.28-52.05, p < 0.001, respectively) and change from first to final PSA per 365 days of 20.0 to 99.9% (adjusted OR 3.40, 95%CI: 3.21-3.60, p < 0.001) and more than 100% (adjusted OR 6.91, 95%CI: 6.29-7.59, p < 0.001) were strongly associated with the diagnosis of prostate cancer. The model performed well when predicting any prostate cancer, clinically significant prostate cancer, and when stratified by age. Conclusions: This study suggests that first PSA in combination with final PSA and rate of change can be used to predict prostate cancer diagnosis. Future studies will be conducted to determine the association with metastatic and lethal prostate cancer.