Real-World Monitoring Strategies and Predictors guiding the Transition from Active Surveillance to Treatment in ISUP 1 Prostate Cancer

Real-World Monitoring Strategies and Predictors guiding the Transition from Active Surveillance to Treatment in ISUP 1 Prostate Cancer | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Real-World Monitoring Strategies and Predictors guiding the Transition from Active Surveillance to Treatment in ISUP 1 Prostate Cancer Giulia Giannini, Amer Mousa, Eberhard Steiner, Nastasiia Artamonova, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6495543/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose Active surveillance (AS) is the standard approach for managing ISUP 1 prostate cancer (PCa), aiming to ensure oncological safety while minimizing overtreatment. However, AS protocols vary significantly. This study assessed a structured AS protocol incorporating PSA kinetics, multiparametric MRI (mpMRI), and targeted biopsies to identify predictors of treatment transition. Methods We retrospectively reviewed 89 patients with ISUP 1 PCa managed with AS between 2010 and 2024. Inclusion criteria were PSA < 10 ng/mL and ≤ 2 positive biopsy cores with ≤ 50% tumor involvement per core. Patients underwent regular PSA testing, mpMRI, and risk-adapted biopsies. Outcomes included treatment conversion, progression predictors, and the role of mpMRI. Results Median follow-up was 52.8 months. PSA was monitored at a median interval of 4.8 months, and mpMRI was performed every 15.7 months (median). At diagnosis, 68.5% underwent mpMRI, with PIRADS 4 as the most frequent finding. During AS, 66.3% underwent at least one re-biopsy, most commonly triggered by PSA progression (73%). Treatment was initiated in 37.1% after a median of 37.9 months due to PSA progression (54.5%), mpMRI changes (21.2%), combined PSA/mpMRI findings (6.1%), histological upgrading (9.1%), or patient preference (3%). Treatments included radical prostatectomy, EBRT or LDR brachytherapy. Among these patients, no PSA persistence was observed; biochemical recurrence occurred in 6.1%, metastases in 4.0%, and overall mortality in 4.5%, with no PCa-specific deaths. Conclusion A structured, risk-adapted AS protocol using PSA kinetics and mpMRI enabled personalized management and timely detection of progression. These findings support the standardization of AS protocols, which should be validated in larger cohorts. Active surveillance ISUP 1 monitoring prostate cancer real world setting predictors for active therapy Introduction Prostate cancer (PCa) is the most frequently diagnosed solid malignancy in men, with highly heterogeneous clinical behavior[ 1 ]. Active surveillance (AS) is the standard approach for managing low-risk PCa, balancing the risks of overtreatment with the need for timely intervention [ 2 ]. Long-term data from large AS cohorts, such as ProtecT and PRIAS, have demonstrated that AS offers prostate cancer-specific survival rates comparable to radical treatments, reinforcing its role as a safe alternative for well-selected patients [ 3 , 4 ]. Despite widespread adoption, AS protocols vary significantly in monitoring strategies and progression criteria. Some studies, such as PRIAS follow fixed biopsy schedules, while others favor a risk-adapted approach incorporating PSA kinetics, multiparametric MRI (mpMRI), and targeted biopsies [ 4 , 5 ]. mpMRI has improved patient selection and progression detection, but standardized MRI-based protocols are lacking [ 5 ]. A further challenge is the absence of standardized criteria for progression. While PSA kinetics are commonly used to guide AS decisions, its reliability has been questioned due to its natural variability, which may not accurately reflect oncological progression [ 6 ] additionally, some patients discontinue AS despite no objective disease worsening, often due to anxiety or uncertainty [ 6 , 7 ]. In this context, incorporating biomarkers such as genomic classifiers (e.g., Prolaris, Decipher) may further enhance risk stratification and optimize treatment decisions. This study aimed to evaluate outcomes in patients managed with a flexible AS protocol incorporating PSA monitoring, mpMRI, and targeted biopsies, specifically addressing: 1) predictors of transition to active treatment; 2) the role of mpMRI in AS management; and 3) oncological outcomes, including upgrading, biochemical recurrence (BCR), and metastases. Patients and Methods We retrospectively reviewed 89 patients diagnosed with International Society of Pathology 1 (ISUP 1) PCa who underwent AS between 2010 and 2024, following approval from the local ethical committee (vote number:1296/2923). Inclusion criteria were: (1) histologically confirmed ISUP 1 PCa, (2) PSA < 10 ng/mL, (3) ≤ 2 positive biopsy cores with ≤ 50% tumor involvement per core, and (4) regular monitoring with PSA, mpMRI, and re-biopsies. Clinical data were extracted from electronic records and included demographics, PSA values, mpMRI findings, and biopsy results. PSA and mpMRI were performed at regular intervals. Biopsies were conducted according to clinical protocols and initiated in cases of PSA progression (PSA > 10 ng/mL, continuous rise over time, or PSA-DT < 12 months) or mpMRI changes. Transition to active treatment was based on histological upgrading, PSA progression, mpMRI progression, or patient choice. Statistical Analysis Continuous variables were described using median and interquartile range. Categorical variables were compared using the chi-square test, while continuous variables were assessed with the Student’s t-test or Mann–Whitney U test. Statistical significance was set at p < 0.05. Analyses were performed using Python (pandas, scipy, statsmodels). Results A total of 89 patients were included in the AS regime, with a median follow-up of 52.8 months (range: 7.23–169.3 months). Median age at diagnosis was 67.8 years (range: 52–86), BMI was 27.2 kg/m² (range: 14.7–37.6) and prostate volume was 52.5 mL (range: 39.6–67.5 mL). Prior to diagnosis, 14.6% had a tumor negative biopsy ( Table 1 ). Table 1 Baseline Patient characteristics and mpMRI findings at baseline. PCa: Prostate Cancer, BMI: Body Mass Index, PSA: Prostate-specific antigen, mpMRI: multiparametric magnetic resonance imaging, PI-RADS: Prostate Imaging Reporting and Data System Variable % Absolute Value Number of patients 89 Follow-up duration (months) (Range) 52.8 (7.23–169.3) Diagnosis via biopsy 94.4% (n = 84) Incidental PCa 5.6% (n = 5) Smokers Yes 7.49% (n = 7) No 74.86% (n = 67) Unknown 17.2% (n = 15) Age (years) 67.8 (52–86) Prostate volume (ml) 52.5 (39.6–67.5) BMI (kg/m²) 27.2 (14.7–37.6) BMI Categories BMI < 18.5 1.1% (n = 1) BMI 18.5–24.9 40.4% (n = 36) BMI 25–29.9 35.9% (n = 32) BMI 30–34.9 8.9% (n = 8) BMI 35–39.9 4.4% (n = 4) BMI ≥ 40 0% (n = 0) PSA at diagnosis 5.51 ng/ml (range: 3.1–8.5) Previous Negative biopsy 14.6% (n = 13) mpMRI before biopsy 68.5% (n = 61) No mpMRI before biopsy 30.3% (n = 27) Unknown mpMRI status 1.1% (n = 1) PIRADS Classification (n = 61) PIRADS 2 1.6% (n = 1) PIRADS 3 9.9% (n = 6) PIRADS 4 80.3% (n = 49) PIRADS 5 8.2% (n = 5) Lesion Localization (n = 66) Apex Lateral Left 18% (n = 12) Apex Lateral Right 14% (n = 9) Base Lateral Left 7.5% (n = 5) Base Lateral Right 14% (n = 9) Peripheral Zone Medial 7.5% (n = 5) Peripheral Zone Right 3% (n = 2) Peripheral Zone Left 17% (n = 11) Transition Zone Right 6% (n = 4) Transition Zone Left 6% (n = 4) Base Anterior Zone 6% (n = 4) Central Zone 1% (n = 1) Lesion Distribution n = 58 Patients with a single lesion 89.7% (n = 52) Patients with multiple lesions 10.3% (n = 6) mpMRI was performed before biopsy in 61 patients (68.5%). Among these, 67.2% (n = 41) were diagnosed in 2018 or later, when mpMRI became recommended. Notably, 32.8% (n = 20) underwent mpMRI despite being diagnosed before 2018. Among patients without mpMRI (30.3%, n = 27), only 14.8% (n = 4) were diagnosed after 2018, suggesting that most of these cases predate routine mpMRI use. mpMRI status was unknown in one patient (1.1%) ( Table 1 ) . Among the 58 patients with mpMRI-detectable lesions, 66 lesions were identified. PIRADS scores were: PIRADS 2 in 1.6%, PIRADS 3 in 9.9%, PIRADS 4 in 80.3%, and PIRADS 5 in 8.2%. Most lesions were located in the apex, peripheral, and transition zones; the full distribution is reported in Table 1 . Notably, 89.7% had a single lesion, while 10.3% presented with multifocal disease. PSA was monitored at a median interval of 4.8 months (range: 3–12 months). 45% of patients had PSA measurements every 3 to 4 months, while 55% had intervals of six months or longer. mpMRI scans were conducted at a median interval of 15.7 months (range: 4–61 months), and repeat biopsies occurred on median every 22.9 months (range: 5.9–96.9 months). PSA progression occurred in 52.8% of patients (n = 47), based on predefined hierarchical criteria: (1) PSA > 10 ng/mL, (2) PSA doubling time (PSA-DT) < 12 months, or (3) a suspicious PSA trend defined as three consecutively rising values with PSA 10 ng/mL, 4.5% both PSA > 10 and PSA-DT < 12 months, 7.9% had PSA-DT 24 months, and in 25.8% PSA-DT could not be calculated due to insufficient or irregular measurements. The median time to PSA progression was 27.3 months (range: 0.7–130.6 months). Re-biopsies were performed in 66.3% of patients (n = 59). Indications included PSA progression alone in 23 patients (39.0%), combined PSA progression and mpMRI changes in 24 (40.6%), and mpMRI progression without PSA changes in 9 (15.2%). One patient (1.7%) was re-biopsied due to missing baseline mpMRI, and in two cases (3.3%) no clear clinical or radiological indication was identified. Biopsies were not scheduled at fixed intervals but were performed based on clinical judgment, with a median interval of 22.9 months (range: 5.8–95.5 months) ( Table 2 ) . Table 2 Clinical parameter during Active Surveillance. PSA: Prostate-specific antigen, mpMRI: multiparametric magnetic resonance imaging, PSA-DT: PSA-Doubling Time. Variable Value PSA Monitoring in months, mean (range) 4.8 (3–12) PSA Interval 3–4 months 45% (n = 40) PSA Interval ≥ 6 months 55% (n = 49) mpMRI monitoring in months, mean (range) 15.7 (4–61) PSA progression 52.8% (n = 47) PSA > 10 ng/mL 24.7% (n = 22) PSA > 10 ng/ml and PSA-DT < 12 months 4.5% (n = 4) PSA-DT 24 months 10.1% (n = 9) PSA-DT not calculable 23.6% (n = 21) Rebiopsy during AS 66% (n = 59) Re-biopsy due to PSA increase without changes on mpMRI 39% (n = 23) PSA > 10 ng/ml 61% (n = 14) PSA > 10 ng/ml and PSA-DT < 12 months 4.3% (n = 1) PSA-DT 10 ng/ml and new lesion 33.3% (n = 8) PSA > 10 ng/ml and PSA-DT < 12 months and new lesion in mpMRI 12.5% (n = 3) PSA-DT < 12 months and new lesion in mpMRI 16.6% (n = 4) Increasing PSA and new lesion in mpMRI 37.5% (n = 9) Re-biopsy due to new lesion on mpMRI without PSA progression 15.2% (n = 9) Absence of baseline mpMRI at diagnosis 1.7% (n = 1) Re-biopsy without a clearly identifiable clinical or radiological indication 3.3% (n = 2) * Suspicious PSA trend : defined as three consecutively rising PSA values, all < 10 ng/mL, in the absence of a calculable PSA doubling time (PSA-DT), often due to ≥ 6-month intervals between measurements. This definition aligns with previous active surveillance literature (e.g., Klotz et al., JCO 2015; Tosoian et al., JCO 2016). Overall, 33 patients (37.1%) transitioned to active therapy after a median duration of 37.9 months (range 10-116.9). PSA progression alone was the indication in 18 patients (54.5%), mpMRI changes without PSA abnormalities in 7 (21.2%), and combined PSA/mMRI progression in 2 (6.1%). Histological upgrading prompted treatment in 3 cases (9.1%). The remaining 3 patients (9.1%) lacked a clear clinical or radiological indication; one case reflected patient preference. Urinary obstructive symptoms were more frequent in treated patients (28.6%) compared to those remaining in AS (14.3%, p = 0.02) ( Table 3 ) . Table 3 Reasons for transition to active treatment and Treatment outcomes and follow-up. PSA: Prostate-specific antigen, mpMRI: mpMRI: multiparametric magnetic resonance imaging, AS: active surveillance, TNM: TNM Classification of Malignant Tumors PSA: Prostate-specific antigen BCR: Biochemical Recurrence Variable Value Patients transitioning to active therapy 33 (37.1%) Median time in AS in months (Range) 37.9 (10–116.9) Transition due mpMRI changes alone 21.2% (n = 7) Transition due to PSA increase 54.5% (n = 18) Transition due to PSA increase and mpMRI changes 6.1% (n = 2) Transition due histological upgrading on re-biopsy 9.1% (n = 3) Patient preference 3% (n = 1) Obstructive symptoms (therapy vs. AS) 28.6% vs. 14.3% (p = 0.02) Patients undergoing active therapy 37.1% (n = 33) Type of therapy Radical prostatectomy 69.7% (n = 23) LDR Brachytherapy 9.1% (n = 3) EBRT 21.2% (n = 7) TNM stage after surgery pT2 91.3% (n = 21) pT2a 38% (n = 8) pT2b 9.5% (n = 2) pT2c 52.5% (n = 11) pT3b 4.3% (n = 1) unknown 4.3% (n = 1) PSA persistence after therapy 0% (n = 0) BCR 6.1% (n = 2) Median follow-up after therapy (months) (range) 22.1 (range 0.1-102.1) Metastatic disease 4% (n = 1) Overall mortality 5.6% (n = 5) Prostate cancer-related deaths 0% Among treated patients, 23 patients (69.7%) underwent radical prostatectomy (RP), 3 patients (9.1%) received an LDR-brachytherapy, and 7 patients (21.2%) underwent external beam radiation therapy (EBRT). Pathology showed pT2 in 91.3% (38% pT2a, 9.5% pT2b, 52.5% pT2c), and pT3b in 4.3%; one case was unknown. No patients experienced PSA persistence post-treatment, and two patients developed a BCR. After a median post-treatment follow-up of 22.1 months (range: 0.1–102.1), 4.0% developed metastases and overall mortality was 5.6%, with no PCa-specific deaths ( Table 3 ) . Discussion AS is increasingly recognized as a safe and effective treatment strategy for managing ISUP 1 PCa, particularly in low-risk patients [ 3 ]. Long-term data from PRIAS, ProtecT, and Tosoian et al. confirm its oncological safety, with survival outcomes comparable to radical treatments [ 4 , 8 , 9 ]. The ProtecT trial, in particular, found no significant difference in prostate cancer-specific mortality among AS, RP, and EBRT after 15 years of follow-up [ 8 ]. Despite its adoption, AS protocols remain heterogeneous, especially regarding PSA testing frequency, imaging, and biopsy strategies. PRIAS mandates biopsies at fixed intervals [ 4 ] other programs promote risk-adapted monitoring, integrating PSA kinetics and mpMRI findings [ 10 ]. This variability highlights the need for a balanced approach that minimizes overtreatment while ensuring oncological safety. Our study contributes to this evolving landscape showing that a flexible AS protocol with risk-based re-biopsy can reduce unnecessary interventions while preserving safety. Although monitoring was tailored to each patient, we applied a structured framework to minimize biopsies without compromising oncological control. PSA was measured every 4.8 months, mpMRI every 15.7 months, and biopsies were performed selectively (median 2–3 per patient). In contrast, PRIAS mandates biopsies at 1, 4, 7, and 10 years, regardless of clinical findings [ 4 ]. Ciccone et al. report a higher biopsy rate during AS (median: 6 biopsies), with upgrading, PSA fluctuations, and patient anxiety as main triggers for treatment [ 11 ]. Their definition of PSA fluctuations, as variations without clear trends, is broader and less defined than our criterion, which required three consecutively rising PSA values despite PSA < 10 ng/mL and non-calculable PSA-DT [ 11 ]. Taneja et al. noted the limitations of PSA alone in detecting progression and the lack of standardized criteria across protocols[ 6 ]. This highlights the importance of incorporating multiple monitoring parameters to minimize unnecessary biopsies and enhance the accuracy of disease progression assessments [ 6 ]. In this context, molecular classifiers (e.g., Prolaris, Decipher) and urinary biomarkers (e.g., SelectMDx, PCA3) are gaining interest as tools to enhance risk stratification [ 12 – 14 ]. Although not yet routinely used, they may support decision-making, especially in borderline cases or when imaging findings are inconclusive. Walker et al. highlighted the marked variability in AS protocols across institutions, particularly regarding biopsy schedules [ 15 ]. Some centers, such as Johns Hopkins (JHU) and PASS, perform annual biopsies, while PRIAS follows a rigid schedule, and the EAU guidelines recommend biopsies only in cases of clinical progression [ 15 ]. This heterogeneity supports the adoption of personalized surveillance strategies, such as our approach combining mpMRI and PSA-DT. Chau Hung Lee et al. highlighted the central role of mpMRI in AS, showing that up to 40% of patients initially eligible based on clinical criteria were reclassified due to imaging findings (ISUP ≥ 2) [ 5 ]. This underscores the value of mpMRI in avoiding underestimation of disease. They also described the PRECISE scoring system, which classifies radiological stability or progression from 1 to 5, prompting biopsy in cases scored 4–5. [ 5 ]. In contrast, our study did not formally apply the PRECISE system, but we used a combined approach integrating PSA-DT, mpMRI findings, and targeted biopsies to monitor disease status. In our study, re-biopsies were performed based on predefined progression indicators, including continuously rising PSA, PSA-DT 10 ng/mL, new mpMRI lesions, or significant lesion growth. Padhani et al. (2021) analyzed the role of mpMRI in guiding biopsy decisions during AS and observed that if MRI findings alone were used, approximately two-thirds of patients could avoid biopsy based on negative or stable imaging. However, this strategy would miss histological upgrading in nearly one-third of progressing cases. Conversely, among patients with mpMRI progression, upgrading was histologically confirmed in only about half, implying a substantial risk of unnecessary biopsies. These findings suggest that while mpMRI can reduce biopsy frequency, it cannot fully replace systematic histological assessment in AS [ 10 ]. The transition to active therapy is a critical endpoint. In our study, 37.1% of patients transitioned to active therapy after a median of 37.9 months This rate is comparable to Klotz et al. (36% at 10 years, 45% at 15 years) and Tosoian et al. (50% at 10 years, 57% at 15 years) [ 9 , 16 ], but higher than PRIAS (21.1%) and lower than Ciccone et al. (47% at 48 months) [ 4 , 11 ]. Davidson Sypre et al. found no significant increase in anxiety or depression among AS patients compared to those treated with RP or RT [ 7 ]. However, in our cohort, 3 patients (9.1%) transitioned to active therapy without documented clinical or radiological progression, and in one case, treatment was explicitly driven by patient preference. This suggests that individual perception of risk may influence decision-making. Similarly, Taneja et al. reported that up to 20% of patients discontinue AS due to psychological reasons or misperceived oncological risk [ 6 ]. n our study, urinary obstructive symptoms were also more common among treated patients, aligning with previous findings linking LUTS to AS discontinuation [ 8 , 15 ]. At final pathology, 91.3% had pT2 and 4.3% had pT3 disease, with no R1 or pN + cases. These outcomes are consistent with PRIAS, but contrast with ProtecT, where 50.5% had Gleason Grade ≥ 2 and 28.5% had pT3/pT4 tumors [ 4 , 8 ]. BCR occured in 6.1% (n = 2), metastases developed in 4.0%, and overall mortality was 5.6%, with no prostate cancer-specific deaths. [ 4 , 8 ]. This study has some limitations. First, the median follow-up of 52.8 months offers robust mid-term data, though shorter than in PRIAS (10 years) and ProtecT (15 years) [ 4 , 8 ]. However, our follow-up is comparable to that of Ciccone et al. (48 months) [ 11 ]. Second, we did not directly assess psychological aspects, but the transition to therapy in a few patients without oncological progression suggests that anxiety or uncertainty may have influenced decisions. Third, molecular biomarkers such as Prolaris or Decipher were not included in risk stratification. While PSA, mpMRI, and biopsies remain standard, genomic classifiers may improve patient selection and reduce overtreatment. Importantly, we are currently conducting a study evaluating the impact of Prolaris on AS decision-making, which may help refine future AS protocols. Fourth, while we employed mpMRI and targeted biopsies to monitor disease progression, we did not formally apply the PRECISE scoring system, which standardizes mpMRI assessment in AS. Instead, progression assessment relied on PSA-DT, imaging, and histological findings. Future research may clarify whether PRECISE adds value to monitoring. Finally, being a single-center study may limit generalizability, though our results align with multicenter AS data. Conclusion AS is a safe and effective strategy for ISUP 1 PCa, with outcomes comparable to long-term AS cohorts. In our study, 37.1% of patients transitioned to active treatment, primarily due to PSA progression (54.5%) or mpMRI changes (21.2%). Only a minority were treated without confirmed progression. These findings underscore the importance of combining mpMRI with PSA kinetics and targeted biopsies in AS protocols. The lack of standardized progression criteria remains a challenge. A risk-adapted approach based on PSA dynamics, imaging, and selective re-biopsy may support clinical decision-making. Future studies should evaluate long-term outcomes and the role of biomarkers to refine risk stratification. Declarations Conflicts of Interest: The authors declare that they have no conflicts of interest. Ethics Approval: This study was approved by the local ethical committee (vote number: 1296/2923). Author Contribution G.G. and I.H. conceived and designed the study. All authors (G.G., A.M., E.S., N.A., M.K., I.H.) contributed to data acquisition. G.G., I.H., and A.M. performed data analysis and interpretation. G.G., I.H., M.K., and N.A. wrote the main manuscript text. G.G., I.H., E.S., and A.M. conducted statistical analyses. E.S. provided administrative, technical, and material support. I.H. supervised the study. All authors critically reviewed, revised, and approved the final manuscript. Data Availability The data that support the findings of this study are available from the corresponding author upon reasonable request. References EAU-EANM-ESTRO-ESUR-ISUP-SIOG-Guidelines-on-Prostate-Cancer-2024_2024-04-09-132035_ypmy_2024-04-16-122605_lqpk n.d. Kinsella N, Helleman J, Bruinsma S, Carlsson S, Cahill D, Brown C, et al. Active surveillance for prostate cancer: a systematic review of contemporary worldwide practices. Transl Androl Urol 2018;7:83–97. https://doi.org/10.21037/tau.2017.12.24. Willemse PPM, Davis NF, Grivas N, Zattoni F, Lardas M, Briers E, et al. Systematic Review of Active Surveillance for Clinically Localised Prostate Cancer to Develop Recommendations Regarding Inclusion of Intermediate-risk Disease, Biopsy Characteristics at Inclusion and Monitoring, and Surveillance Repeat Biopsy Strategy. Eur Urol 2022;81:337–46. https://doi.org/10.1016/j.eururo.2021.12.007. Bul M, Zhu X, Valdagni R, Pickles T, Kakehi Y, Rannikko A, et al. Active surveillance for low-risk prostate cancer worldwide: The PRIAS study. Eur Urol 2013;63:597–603. https://doi.org/10.1016/j.eururo.2012.11.005. Lee H, Byun S-S, Lee SE, Hong SK. Impact of poor glycemic control upon clinical outcomes after radical prostatectomy in localized prostate cancer. Sci Rep 2021;11:12002. https://doi.org/10.1038/s41598-021-91310-3. Taneja SS. Re: Five-year nationwide follow-up study of active surveillance for prostate cancer. Journal of Urology 2015;193:1981–3. https://doi.org/10.1016/j.juro.2015.03.043. Sypre D, Pignot G, Touzani R, Marino P, Walz J, Rybikowski S, et al. Impact of active surveillance for prostate cancer on the risk of depression and anxiety. Sci Rep 2022;12. https://doi.org/10.1038/s41598-022-17224-w. Alberti A, Nicoletti R, Castellani D, Yuan Y, Maggi M, Dibilio E, et al. Patient-reported Outcome Measures and Experience Measures After Active Surveillance Versus Radiation Therapy Versus Radical Prostatectomy for Prostate Cancer: A Systematic Review of Prospective Comparative Studies. Eur Urol Oncol 2024. https://doi.org/10.1016/j.euo.2024.05.008. Tosoian JJ, Loeb S, Epstein JI, Turkbey B, Choyke PL, Schaeffer EM. Active Surveillance of Prostate Cancer: Use, Outcomes, Imaging, and Diagnostic Tools. American Society of Clinical Oncology Educational Book 2016;36:e235–45. https://doi.org/10.14694/edbk_159244. Padhani AR, Rouvière O, Schoots IG. Magnetic Resonance Imaging for Tailoring the Need to Biopsy During Follow-up for Men on Active Surveillance for Prostate Cancer. Eur Urol 2021;80:564–6. https://doi.org/10.1016/j.eururo.2021.05.024. Ciccone G, De Luca S, Oderda M, Munoz F, Krengli M, Allis S, et al. Patient and Context Factors in the Adoption of Active Surveillance for Low-Risk Prostate Cancer. JAMA Netw Open 2023:E2338039. https://doi.org/10.1001/jamanetworkopen.2023.38039. Wei JT. Urinary biomarkers for prostate cancer. Curr Opin Urol 2015;25:77–82. https://doi.org/10.1097/MOU.0000000000000133. Deluce JE, Cardenas L, Lalani A-K, Maleki Vareki S, Fernandes R. Emerging Biomarker-Guided Therapies in Prostate Cancer. Curr Oncol 2022;29:5054–76. https://doi.org/10.3390/curroncol29070400. Shore N, Concepcion R, Saltzstein D, Lucia MS, van Breda A, Welbourn W, et al. Clinical utility of a biopsy-based cell cycle gene expression assay in localized prostate cancer. Curr Med Res Opin 2014;30:547–53. https://doi.org/10.1185/03007995.2013.873398. Walker CH, Marchetti KA, Singhal U, Morgan TM. Active surveillance for prostate cancer: selection criteria, guidelines, and outcomes. World J Urol 2022;40:35–42. https://doi.org/10.1007/s00345-021-03622-8. Klotz L, Vesprini D, Sethukavalan P, Jethava V, Zhang L, Jain S, et al. Long-Term Follow-Up of a Large Active Surveillance Cohort of Patients With Prostate Cancer. Journal of Clinical Oncology 2015;33:272–7. https://doi.org/10.1200/JCO.2014.55.1192. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6495543","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":452565758,"identity":"d726ef7a-96c8-4a0b-a7f6-3b3b298d6408","order_by":0,"name":"Giulia Giannini","email":"","orcid":"","institution":"Tirol Kliniken","correspondingAuthor":false,"prefix":"","firstName":"Giulia","middleName":"","lastName":"Giannini","suffix":""},{"id":452565759,"identity":"cae24f1f-08a1-4b7b-be57-1a09faf4443c","order_by":1,"name":"Amer Mousa","email":"","orcid":"","institution":"Medical University Innsbruck","correspondingAuthor":false,"prefix":"","firstName":"Amer","middleName":"","lastName":"Mousa","suffix":""},{"id":452565760,"identity":"837448f8-276d-4d41-b61a-7190859933b7","order_by":2,"name":"Eberhard Steiner","email":"","orcid":"","institution":"Tirol Kliniken","correspondingAuthor":false,"prefix":"","firstName":"Eberhard","middleName":"","lastName":"Steiner","suffix":""},{"id":452565761,"identity":"5c1d33d7-1078-4e74-993a-80b67bda044c","order_by":3,"name":"Nastasiia Artamonova","email":"","orcid":"","institution":"Medical University Innsbruck","correspondingAuthor":false,"prefix":"","firstName":"Nastasiia","middleName":"","lastName":"Artamonova","suffix":""},{"id":452565762,"identity":"68a39987-8582-466f-9033-2a58a824ee8d","order_by":4,"name":"Mona Kafka","email":"","orcid":"","institution":"Medical University Innsbruck","correspondingAuthor":false,"prefix":"","firstName":"Mona","middleName":"","lastName":"Kafka","suffix":""},{"id":452565764,"identity":"9a9763da-dfdf-4477-a04f-f13d23cef563","order_by":5,"name":"Isabel Heidegger","email":"data:image/png;base64,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","orcid":"","institution":"Medical University Innsbruck","correspondingAuthor":true,"prefix":"","firstName":"Isabel","middleName":"","lastName":"Heidegger","suffix":""}],"badges":[],"createdAt":"2025-04-21 11:23:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6495543/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6495543/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":84371710,"identity":"9b2f7219-9a18-402d-8948-f36fffdb0a2d","added_by":"auto","created_at":"2025-06-11 07:32:13","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1110121,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6495543/v1/2c3afe90-ecd5-48d5-a7f0-45663ba0e5e9.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Real-World Monitoring Strategies and Predictors guiding the Transition from Active Surveillance to Treatment in ISUP 1 Prostate Cancer","fulltext":[{"header":"Introduction","content":"\u003cp\u003eProstate cancer (PCa) is the most frequently diagnosed solid malignancy in men, with highly heterogeneous clinical behavior[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Active surveillance (AS) is the standard approach for managing low-risk PCa, balancing the risks of overtreatment with the need for timely intervention [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Long-term data from large AS cohorts, such as ProtecT and PRIAS, have demonstrated that AS offers prostate cancer-specific survival rates comparable to radical treatments, reinforcing its role as a safe alternative for well-selected patients [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDespite widespread adoption, AS protocols vary significantly in monitoring strategies and progression criteria. Some studies, such as PRIAS follow fixed biopsy schedules, while others favor a risk-adapted approach incorporating PSA kinetics, multiparametric MRI (mpMRI), and targeted biopsies [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. mpMRI has improved patient selection and progression detection, but standardized MRI-based protocols are lacking [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eA further challenge is the absence of standardized criteria for progression. While PSA kinetics are commonly used to guide AS decisions, its reliability has been questioned due to its natural variability, which may not accurately reflect oncological progression [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] additionally, some patients discontinue AS despite no objective disease worsening, often due to anxiety or uncertainty [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. In this context, incorporating biomarkers such as genomic classifiers (e.g., Prolaris, Decipher) may further enhance risk stratification and optimize treatment decisions.\u003c/p\u003e \u003cp\u003eThis study aimed to evaluate outcomes in patients managed with a flexible AS protocol incorporating PSA monitoring, mpMRI, and targeted biopsies, specifically addressing: 1) predictors of transition to active treatment; 2) the role of mpMRI in AS management; and 3) oncological outcomes, including upgrading, biochemical recurrence (BCR), and metastases.\u003c/p\u003e"},{"header":"Patients and Methods","content":"\u003cp\u003e We retrospectively reviewed 89 patients diagnosed with International Society of Pathology 1 (ISUP 1) PCa who underwent AS between 2010 and 2024, following approval from the local ethical committee (vote number:1296/2923). Inclusion criteria were: (1) histologically confirmed ISUP 1 PCa, (2) PSA\u0026thinsp;\u0026lt;\u0026thinsp;10 ng/mL, (3)\u0026thinsp;\u0026le;\u0026thinsp;2 positive biopsy cores with \u0026le;\u0026thinsp;50% tumor involvement per core, and (4) regular monitoring with PSA, mpMRI, and re-biopsies. Clinical data were extracted from electronic records and included demographics, PSA values, mpMRI findings, and biopsy results. PSA and mpMRI were performed at regular intervals. Biopsies were conducted according to clinical protocols and initiated in cases of PSA progression (PSA\u0026thinsp;\u0026gt;\u0026thinsp;10 ng/mL, continuous rise over time, or PSA-DT\u0026thinsp;\u0026lt;\u0026thinsp;12 months) or mpMRI changes. Transition to active treatment was based on histological upgrading, PSA progression, mpMRI progression, or patient choice.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eContinuous variables were described using median and interquartile range. Categorical variables were compared using the chi-square test, while continuous variables were assessed with the Student\u0026rsquo;s t-test or Mann\u0026ndash;Whitney U test. Statistical significance was set at p\u0026thinsp;\u0026lt;\u0026thinsp;0.05. Analyses were performed using Python (pandas, scipy, statsmodels).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 89 patients were included in the AS regime, with a median follow-up of 52.8 months (range: 7.23\u0026ndash;169.3 months). Median age at diagnosis was 67.8 years (range: 52\u0026ndash;86), BMI was 27.2 kg/m\u0026sup2; (range: 14.7\u0026ndash;37.6) and prostate volume was 52.5 mL (range: 39.6\u0026ndash;67.5 mL). Prior to diagnosis, 14.6% had a tumor negative biopsy \u003cb\u003e(\u003c/b\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u003cb\u003e).\u003c/b\u003e\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003e\u003cb\u003eBaseline Patient characteristics and mpMRI findings at baseline.\u003c/b\u003e PCa: Prostate Cancer, BMI: Body Mass Index, PSA: Prostate-specific antigen, mpMRI: multiparametric magnetic resonance imaging, PI-RADS: Prostate Imaging Reporting and Data System\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e%\u003c/p\u003e \u003cp\u003eAbsolute Value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNumber of patients\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e89\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFollow-up duration (months)\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e(Range)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e52.8\u003c/p\u003e \u003cp\u003e(7.23\u0026ndash;169.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDiagnosis via biopsy\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e94.4%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;84)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eIncidental PCa\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.6%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSmokers\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.49%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e74.86%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;67)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17.2%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;15)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge (years)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e67.8 (52\u0026ndash;86)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eProstate volume (ml)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e52.5 (39.6\u0026ndash;67.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBMI (kg/m\u0026sup2;)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27.2 (14.7\u0026ndash;37.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBMI Categories\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI\u0026thinsp;\u0026lt;\u0026thinsp;18.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.1%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI 18.5\u0026ndash;24.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40.4%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;36)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI 25\u0026ndash;29.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35.9%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;32)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI 30\u0026ndash;34.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.9%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI 35\u0026ndash;39.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.4%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI\u0026thinsp;\u0026ge;\u0026thinsp;40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePSA at diagnosis\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.51 ng/ml (range: 3.1\u0026ndash;8.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePrevious Negative biopsy\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14.6%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;13)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003empMRI before biopsy\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e68.5%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;61)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNo mpMRI before biopsy\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30.3%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;27)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eUnknown mpMRI status\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.1%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePIRADS Classification (n\u0026thinsp;=\u0026thinsp;61)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePIRADS 2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.6%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePIRADS 3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9.9%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePIRADS 4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e80.3%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;49)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePIRADS 5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.2%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLesion Localization\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;66)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eApex Lateral Left\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;12)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eApex Lateral Right\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBase Lateral Left\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.5%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBase Lateral Right\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePeripheral Zone Medial\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.5%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePeripheral Zone Right\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePeripheral Zone Left\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;11)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTransition Zone Right\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTransition Zone Left\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBase Anterior Zone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCentral Zone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLesion Distribution\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;58\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatients with a single lesion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e89.7%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;52)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatients with multiple lesions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10.3%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003empMRI was performed before biopsy in 61 patients (68.5%). Among these, 67.2% (n\u0026thinsp;=\u0026thinsp;41) were diagnosed in 2018 or later, when mpMRI became recommended. Notably, 32.8% (n\u0026thinsp;=\u0026thinsp;20) underwent mpMRI despite being diagnosed before 2018. Among patients without mpMRI (30.3%, n\u0026thinsp;=\u0026thinsp;27), only 14.8% (n\u0026thinsp;=\u0026thinsp;4) were diagnosed after 2018, suggesting that most of these cases predate routine mpMRI use. mpMRI status was unknown in one patient (1.1%) \u003cb\u003e(\u003c/b\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e.\u003c/p\u003e \u003cp\u003eAmong the 58 patients with mpMRI-detectable lesions, 66 lesions were identified. PIRADS scores were: PIRADS 2 in 1.6%, PIRADS 3 in 9.9%, PIRADS 4 in 80.3%, and PIRADS 5 in 8.2%. Most lesions were located in the apex, peripheral, and transition zones; the full distribution is reported in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Notably, 89.7% had a single lesion, while 10.3% presented with multifocal disease.\u003c/p\u003e \u003cp\u003ePSA was monitored at a median interval of 4.8 months (range: 3\u0026ndash;12 months). 45% of patients had PSA measurements every 3 to 4 months, while 55% had intervals of six months or longer. mpMRI scans were conducted at a median interval of 15.7 months (range: 4\u0026ndash;61 months), and repeat biopsies occurred on median every 22.9 months (range: 5.9\u0026ndash;96.9 months).\u003c/p\u003e \u003cp\u003ePSA progression occurred in 52.8% of patients (n\u0026thinsp;=\u0026thinsp;47), based on predefined hierarchical criteria: (1) PSA\u0026thinsp;\u0026gt;\u0026thinsp;10 ng/mL, (2) PSA doubling time (PSA-DT)\u0026thinsp;\u0026lt;\u0026thinsp;12 months, or (3) a suspicious PSA trend defined as three consecutively rising values with PSA\u0026thinsp;\u0026lt;\u0026thinsp;10 ng/mL and non-calculable PSA-DT. Specifically, 24.7% had PSA\u0026thinsp;\u0026gt;\u0026thinsp;10 ng/mL, 4.5% both PSA\u0026thinsp;\u0026gt;\u0026thinsp;10 and PSA-DT\u0026thinsp;\u0026lt;\u0026thinsp;12 months, 7.9% had PSA-DT\u0026thinsp;\u0026lt;\u0026thinsp;12 months without elevated PSA, and 15.7% met only the trend criterion. Additionally, 22.5% had a PSA-DT between 12 and 24 months, 10.1% \u0026gt;24 months, and in 25.8% PSA-DT could not be calculated due to insufficient or irregular measurements.\u003c/p\u003e \u003cp\u003eThe median time to PSA progression was 27.3 months (range: 0.7\u0026ndash;130.6 months). Re-biopsies were performed in 66.3% of patients (n\u0026thinsp;=\u0026thinsp;59). Indications included PSA progression alone in 23 patients (39.0%), combined PSA progression and mpMRI changes in 24 (40.6%), and mpMRI progression without PSA changes in 9 (15.2%). One patient (1.7%) was re-biopsied due to missing baseline mpMRI, and in two cases (3.3%) no clear clinical or radiological indication was identified. Biopsies were not scheduled at fixed intervals but were performed based on clinical judgment, with a median interval of 22.9 months (range: 5.8\u0026ndash;95.5 months) \u003cb\u003e(\u003c/b\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003e\u003cb\u003eClinical parameter during Active Surveillance.\u003c/b\u003e PSA: Prostate-specific antigen, mpMRI: multiparametric magnetic resonance imaging, PSA-DT: PSA-Doubling Time.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eValue\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePSA Monitoring in months, mean\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e(range)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.8\u003c/p\u003e \u003cp\u003e(3\u0026ndash;12)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePSA Interval 3\u0026ndash;4 months\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e45%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;40)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePSA Interval\u0026thinsp;\u0026ge;\u0026thinsp;6 months\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e55%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;49)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003empMRI monitoring in months, mean\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e(range)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15.7\u003c/p\u003e \u003cp\u003e(4\u0026ndash;61)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePSA progression\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e52.8%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;47)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePSA\u0026thinsp;\u0026gt;\u0026thinsp;10 ng/mL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24.7%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;22)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePSA\u0026thinsp;\u0026gt;\u0026thinsp;10 ng/ml and PSA-DT\u0026thinsp;\u0026lt;\u0026thinsp;12 months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.5%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePSA-DT\u0026thinsp;\u0026lt;\u0026thinsp;12 months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.9%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSuspicious PSA trend*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15.7%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;14)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNo PSA progression\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e47.2%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;42)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePSA-DT 12\u0026ndash;24 months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13.5%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;12)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePSA-DT\u0026thinsp;\u0026gt;\u0026thinsp;24 months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10.1%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePSA-DT not calculable\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23.6%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;21)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRebiopsy during AS\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e66%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;59)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eRe-biopsy due to PSA increase without changes on mpMRI\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;23)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePSA\u0026thinsp;\u0026gt;\u0026thinsp;10 ng/ml\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e61%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;14)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePSA\u0026thinsp;\u0026gt;\u0026thinsp;10 ng/ml and PSA-DT\u0026thinsp;\u0026lt;\u0026thinsp;12 months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.3%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePSA-DT\u0026thinsp;\u0026lt;\u0026thinsp;12 months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePSA with suspicious trend only\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eRe-biopsy due to combined PSA and mpMRI changes\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40.6%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;24)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePSA\u0026thinsp;\u0026gt;\u0026thinsp;10 ng/ml and new lesion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33.3%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePSA\u0026thinsp;\u0026gt;\u0026thinsp;10 ng/ml and PSA-DT\u0026thinsp;\u0026lt;\u0026thinsp;12 months and new lesion in mpMRI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12.5%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePSA-DT\u0026thinsp;\u0026lt;\u0026thinsp;12 months and new lesion in mpMRI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16.6%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIncreasing PSA and new lesion in mpMRI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e37.5%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eRe-biopsy due to new lesion on mpMRI without PSA progression\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15.2%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eAbsence of baseline mpMRI at diagnosis\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.7%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eRe-biopsy without a clearly identifiable clinical or radiological indication\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.3%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003e*\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eSuspicious PSA trend\u003c/span\u003e: defined as three consecutively rising PSA values, all \u0026lt;\u0026thinsp;10 ng/mL, in the absence of a calculable PSA doubling time (PSA-DT), often due to \u0026ge;\u0026thinsp;6-month intervals between measurements. This definition aligns with previous active surveillance literature (e.g., Klotz et al., JCO 2015; Tosoian et al., JCO 2016).\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eOverall, 33 patients (37.1%) transitioned to active therapy after a median duration of 37.9 months (range 10-116.9). PSA progression alone was the indication in 18 patients (54.5%), mpMRI changes without PSA abnormalities in 7 (21.2%), and combined PSA/mMRI progression in 2 (6.1%). Histological upgrading prompted treatment in 3 cases (9.1%). The remaining 3 patients (9.1%) lacked a clear clinical or radiological indication; one case reflected patient preference. Urinary obstructive symptoms were more frequent in treated patients (28.6%) compared to those remaining in AS (14.3%, p\u0026thinsp;=\u0026thinsp;0.02) \u003cb\u003e(\u003c/b\u003eTable\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003e\u003cb\u003eReasons for transition to active treatment and Treatment outcomes and follow-up.\u003c/b\u003e PSA: Prostate-specific antigen, mpMRI: mpMRI: multiparametric magnetic resonance imaging, AS: active surveillance, TNM: TNM Classification of Malignant Tumors PSA: Prostate-specific antigen BCR: Biochemical Recurrence\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eValue\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePatients transitioning to active therapy\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33 (37.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMedian time in AS in months\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e(Range)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e37.9\u003c/p\u003e \u003cp\u003e(10\u0026ndash;116.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTransition due mpMRI changes alone\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21.2%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTransition due to PSA increase\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e54.5%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;18)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTransition due to PSA increase and mpMRI changes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.1%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTransition due histological upgrading on re-biopsy\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9.1%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePatient preference\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eObstructive symptoms (therapy vs. AS)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28.6% vs. 14.3%\u003c/p\u003e \u003cp\u003e(p\u0026thinsp;=\u0026thinsp;0.02)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePatients undergoing active therapy\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e37.1%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;33)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eType of therapy\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRadical prostatectomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e69.7%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;23)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLDR Brachytherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9.1%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEBRT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21.2%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTNM stage after surgery\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003epT2\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e91.3%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;21)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003epT2a\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003epT2b\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9.5%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003epT2c\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e52.5%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;11)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003epT3b\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.3%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eunknown\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.3%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePSA persistence after therapy\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBCR\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.1%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMedian follow-up after therapy (months)\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e(range)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22.1\u003c/p\u003e \u003cp\u003e(range 0.1-102.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMetastatic disease\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eOverall mortality\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.6%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eProstate cancer-related deaths\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAmong treated patients, 23 patients (69.7%) underwent radical prostatectomy (RP), 3 patients (9.1%) received an LDR-brachytherapy, and 7 patients (21.2%) underwent external beam radiation therapy (EBRT). Pathology showed pT2 in 91.3% (38% pT2a, 9.5% pT2b, 52.5% pT2c), and pT3b in 4.3%; one case was unknown. No patients experienced PSA persistence post-treatment, and two patients developed a BCR. After a median post-treatment follow-up of 22.1 months (range: 0.1\u0026ndash;102.1), 4.0% developed metastases and overall mortality was 5.6%, with no PCa-specific deaths \u003cb\u003e(\u003c/b\u003eTable\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eAS is increasingly recognized as a safe and effective treatment strategy for managing ISUP 1 PCa, particularly in low-risk patients [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Long-term data from PRIAS, ProtecT, and Tosoian et al. confirm its oncological safety, with survival outcomes comparable to radical treatments [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. The ProtecT trial, in particular, found no significant difference in prostate cancer-specific mortality among AS, RP, and EBRT after 15 years of follow-up [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDespite its adoption, AS protocols remain heterogeneous, especially regarding PSA testing frequency, imaging, and biopsy strategies. PRIAS mandates biopsies at fixed intervals [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] other programs promote risk-adapted monitoring, integrating PSA kinetics and mpMRI findings [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. This variability highlights the need for a balanced approach that minimizes overtreatment while ensuring oncological safety. Our study contributes to this evolving landscape showing that a flexible AS protocol with risk-based re-biopsy can reduce unnecessary interventions while preserving safety.\u003c/p\u003e \u003cp\u003eAlthough monitoring was tailored to each patient, we applied a structured framework to minimize biopsies without compromising oncological control. PSA was measured every 4.8 months, mpMRI every 15.7 months, and biopsies were performed selectively (median 2\u0026ndash;3 per patient). In contrast, PRIAS mandates biopsies at 1, 4, 7, and 10 years, regardless of clinical findings [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Ciccone et al. report a higher biopsy rate during AS (median: 6 biopsies), with upgrading, PSA fluctuations, and patient anxiety as main triggers for treatment [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Their definition of PSA fluctuations, as variations without clear trends, is broader and less defined than our criterion, which required three consecutively rising PSA values despite PSA\u0026thinsp;\u0026lt;\u0026thinsp;10 ng/mL and non-calculable PSA-DT [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eTaneja et al. noted the limitations of PSA alone in detecting progression and the lack of standardized criteria across protocols[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. This highlights the importance of incorporating multiple monitoring parameters to minimize unnecessary biopsies and enhance the accuracy of disease progression assessments [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. In this context, molecular classifiers (e.g., Prolaris, Decipher) and urinary biomarkers (e.g., SelectMDx, PCA3) are gaining interest as tools to enhance risk stratification [\u003cspan additionalcitationids=\"CR13\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Although not yet routinely used, they may support decision-making, especially in borderline cases or when imaging findings are inconclusive. Walker et al. highlighted the marked variability in AS protocols across institutions, particularly regarding biopsy schedules [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Some centers, such as Johns Hopkins (JHU) and PASS, perform annual biopsies, while PRIAS follows a rigid schedule, and the EAU guidelines recommend biopsies only in cases of clinical progression [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. This heterogeneity supports the adoption of personalized surveillance strategies, such as our approach combining mpMRI and PSA-DT.\u003c/p\u003e \u003cp\u003eChau Hung Lee et al. highlighted the central role of mpMRI in AS, showing that up to 40% of patients initially eligible based on clinical criteria were reclassified due to imaging findings (ISUP\u0026thinsp;\u0026ge;\u0026thinsp;2) [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. This underscores the value of mpMRI in avoiding underestimation of disease. They also described the PRECISE scoring system, which classifies radiological stability or progression from 1 to 5, prompting biopsy in cases scored 4\u0026ndash;5. [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. In contrast, our study did not formally apply the PRECISE system, but we used a combined approach integrating PSA-DT, mpMRI findings, and targeted biopsies to monitor disease status.\u003c/p\u003e \u003cp\u003eIn our study, re-biopsies were performed based on predefined progression indicators, including continuously rising PSA, PSA-DT\u0026thinsp;\u0026lt;\u0026thinsp;12 months, PSA\u0026thinsp;\u0026gt;\u0026thinsp;10 ng/mL, new mpMRI lesions, or significant lesion growth.\u003c/p\u003e \u003cp\u003ePadhani et al. (2021) analyzed the role of mpMRI in guiding biopsy decisions during AS and observed that if MRI findings alone were used, approximately two-thirds of patients could avoid biopsy based on negative or stable imaging. However, this strategy would miss histological upgrading in nearly one-third of progressing cases. Conversely, among patients with mpMRI progression, upgrading was histologically confirmed in only about half, implying a substantial risk of unnecessary biopsies. These findings suggest that while mpMRI can reduce biopsy frequency, it cannot fully replace systematic histological assessment in AS [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe transition to active therapy is a critical endpoint. In our study, 37.1% of patients transitioned to active therapy after a median of 37.9 months This rate is comparable to Klotz et al. (36% at 10 years, 45% at 15 years) and Tosoian et al. (50% at 10 years, 57% at 15 years) [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e], but higher than PRIAS (21.1%) and lower than Ciccone et al. (47% at 48 months) [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDavidson Sypre et al. found no significant increase in anxiety or depression among AS patients compared to those treated with RP or RT [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. However, in our cohort, 3 patients (9.1%) transitioned to active therapy without documented clinical or radiological progression, and in one case, treatment was explicitly driven by patient preference. This suggests that individual perception of risk may influence decision-making. Similarly, Taneja et al. reported that up to 20% of patients discontinue AS due to psychological reasons or misperceived oncological risk [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. n our study, urinary obstructive symptoms were also more common among treated patients, aligning with previous findings linking LUTS to AS discontinuation [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAt final pathology, 91.3% had pT2 and 4.3% had pT3 disease, with no R1 or pN\u0026thinsp;+\u0026thinsp;cases. These outcomes are consistent with PRIAS, but contrast with ProtecT, where 50.5% had Gleason Grade\u0026thinsp;\u0026ge;\u0026thinsp;2 and 28.5% had pT3/pT4 tumors [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. BCR occured in 6.1% (n\u0026thinsp;=\u0026thinsp;2), metastases developed in 4.0%, and overall mortality was 5.6%, with no prostate cancer-specific deaths. [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThis study has some limitations. First, the median follow-up of 52.8 months offers robust mid-term data, though shorter than in PRIAS (10 years) and ProtecT (15 years) [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. However, our follow-up is comparable to that of Ciccone et al. (48 months) [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Second, we did not directly assess psychological aspects, but the transition to therapy in a few patients without oncological progression suggests that anxiety or uncertainty may have influenced decisions. Third, molecular biomarkers such as Prolaris or Decipher were not included in risk stratification. While PSA, mpMRI, and biopsies remain standard, genomic classifiers may improve patient selection and reduce overtreatment. Importantly, we are currently conducting a study evaluating the impact of Prolaris on AS decision-making, which may help refine future AS protocols. Fourth, while we employed mpMRI and targeted biopsies to monitor disease progression, we did not formally apply the PRECISE scoring system, which standardizes mpMRI assessment in AS. Instead, progression assessment relied on PSA-DT, imaging, and histological findings. Future research may clarify whether PRECISE adds value to monitoring. Finally, being a single-center study may limit generalizability, though our results align with multicenter AS data.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eAS is a safe and effective strategy for ISUP 1 PCa, with outcomes comparable to long-term AS cohorts. In our study, 37.1% of patients transitioned to active treatment, primarily due to PSA progression (54.5%) or mpMRI changes (21.2%). Only a minority were treated without confirmed progression. These findings underscore the importance of combining mpMRI with PSA kinetics and targeted biopsies in AS protocols. The lack of standardized progression criteria remains a challenge. A risk-adapted approach based on PSA dynamics, imaging, and selective re-biopsy may support clinical decision-making. Future studies should evaluate long-term outcomes and the role of biomarkers to refine risk stratification.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003cstrong\u003eConflicts of Interest:\u003c/strong\u003e \u003cp\u003e \u003cb\u003eThe\u003c/b\u003e authors declare that they have no conflicts of interest.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eEthics Approval:\u003c/strong\u003e \u003cp\u003e This study was approved by the local ethical committee (vote number: 1296/2923).\u003c/p\u003e \u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eG.G. and I.H. conceived and designed the study. All authors (G.G., A.M., E.S., N.A., M.K., I.H.) contributed to data acquisition. G.G., I.H., and A.M. performed data analysis and interpretation. G.G., I.H., M.K., and N.A. wrote the main manuscript text. G.G., I.H., E.S., and A.M. conducted statistical analyses. E.S. provided administrative, technical, and material support. I.H. supervised the study. All authors critically reviewed, revised, and approved the final manuscript.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe data that support the findings of this study are available from the corresponding author upon reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eEAU-EANM-ESTRO-ESUR-ISUP-SIOG-Guidelines-on-Prostate-Cancer-2024_2024-04-09-132035_ypmy_2024-04-16-122605_lqpk n.d.\u003c/li\u003e\n\u003cli\u003eKinsella N, Helleman J, Bruinsma S, Carlsson S, Cahill D, Brown C, et al. Active surveillance for prostate cancer: a systematic review of contemporary worldwide practices. Transl Androl Urol 2018;7:83\u0026ndash;97. https://doi.org/10.21037/tau.2017.12.24.\u003c/li\u003e\n\u003cli\u003eWillemse PPM, Davis NF, Grivas N, Zattoni F, Lardas M, Briers E, et al. Systematic Review of Active Surveillance for Clinically Localised Prostate Cancer to Develop Recommendations Regarding Inclusion of Intermediate-risk Disease, Biopsy Characteristics at Inclusion and Monitoring, and Surveillance Repeat Biopsy Strategy. Eur Urol 2022;81:337\u0026ndash;46. https://doi.org/10.1016/j.eururo.2021.12.007.\u003c/li\u003e\n\u003cli\u003eBul M, Zhu X, Valdagni R, Pickles T, Kakehi Y, Rannikko A, et al. Active surveillance for low-risk prostate cancer worldwide: The PRIAS study. Eur Urol 2013;63:597\u0026ndash;603. https://doi.org/10.1016/j.eururo.2012.11.005.\u003c/li\u003e\n\u003cli\u003eLee H, Byun S-S, Lee SE, Hong SK. Impact of poor glycemic control upon clinical outcomes after radical prostatectomy in localized prostate cancer. Sci Rep 2021;11:12002. https://doi.org/10.1038/s41598-021-91310-3.\u003c/li\u003e\n\u003cli\u003eTaneja SS. Re: Five-year nationwide follow-up study of active surveillance for prostate cancer. Journal of Urology 2015;193:1981\u0026ndash;3. https://doi.org/10.1016/j.juro.2015.03.043.\u003c/li\u003e\n\u003cli\u003eSypre D, Pignot G, Touzani R, Marino P, Walz J, Rybikowski S, et al. Impact of active surveillance for prostate cancer on the risk of depression and anxiety. Sci Rep 2022;12. https://doi.org/10.1038/s41598-022-17224-w.\u003c/li\u003e\n\u003cli\u003eAlberti A, Nicoletti R, Castellani D, Yuan Y, Maggi M, Dibilio E, et al. Patient-reported Outcome Measures and Experience Measures After Active Surveillance Versus Radiation Therapy Versus Radical Prostatectomy for Prostate Cancer: A Systematic Review of Prospective Comparative Studies. Eur Urol Oncol 2024. https://doi.org/10.1016/j.euo.2024.05.008.\u003c/li\u003e\n\u003cli\u003eTosoian JJ, Loeb S, Epstein JI, Turkbey B, Choyke PL, Schaeffer EM. Active Surveillance of Prostate Cancer: Use, Outcomes, Imaging, and Diagnostic Tools. American Society of Clinical Oncology Educational Book 2016;36:e235\u0026ndash;45. https://doi.org/10.14694/edbk_159244.\u003c/li\u003e\n\u003cli\u003ePadhani AR, Rouvi\u0026egrave;re O, Schoots IG. Magnetic Resonance Imaging for Tailoring the Need to Biopsy During Follow-up for Men on Active Surveillance for Prostate Cancer. Eur Urol 2021;80:564\u0026ndash;6. https://doi.org/10.1016/j.eururo.2021.05.024.\u003c/li\u003e\n\u003cli\u003eCiccone G, De Luca S, Oderda M, Munoz F, Krengli M, Allis S, et al. Patient and Context Factors in the Adoption of Active Surveillance for Low-Risk Prostate Cancer. JAMA Netw Open 2023:E2338039. https://doi.org/10.1001/jamanetworkopen.2023.38039.\u003c/li\u003e\n\u003cli\u003eWei JT. Urinary biomarkers for prostate cancer. Curr Opin Urol 2015;25:77\u0026ndash;82. https://doi.org/10.1097/MOU.0000000000000133.\u003c/li\u003e\n\u003cli\u003eDeluce JE, Cardenas L, Lalani A-K, Maleki Vareki S, Fernandes R. Emerging Biomarker-Guided Therapies in Prostate Cancer. Curr Oncol 2022;29:5054\u0026ndash;76. https://doi.org/10.3390/curroncol29070400.\u003c/li\u003e\n\u003cli\u003eShore N, Concepcion R, Saltzstein D, Lucia MS, van Breda A, Welbourn W, et al. Clinical utility of a biopsy-based cell cycle gene expression assay in localized prostate cancer. Curr Med Res Opin 2014;30:547\u0026ndash;53. https://doi.org/10.1185/03007995.2013.873398.\u003c/li\u003e\n\u003cli\u003eWalker CH, Marchetti KA, Singhal U, Morgan TM. Active surveillance for prostate cancer: selection criteria, guidelines, and outcomes. World J Urol 2022;40:35\u0026ndash;42. https://doi.org/10.1007/s00345-021-03622-8.\u003c/li\u003e\n\u003cli\u003eKlotz L, Vesprini D, Sethukavalan P, Jethava V, Zhang L, Jain S, et al. Long-Term Follow-Up of a Large Active Surveillance Cohort of Patients With Prostate Cancer. Journal of Clinical Oncology 2015;33:272\u0026ndash;7. https://doi.org/10.1200/JCO.2014.55.1192.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Active surveillance, ISUP 1, monitoring, prostate cancer, real world setting, predictors for active therapy","lastPublishedDoi":"10.21203/rs.3.rs-6495543/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6495543/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eActive surveillance (AS) is the standard approach for managing ISUP 1 prostate cancer (PCa), aiming to ensure oncological safety while minimizing overtreatment. However, AS protocols vary significantly. This study assessed a structured AS protocol incorporating PSA kinetics, multiparametric MRI (mpMRI), and targeted biopsies to identify predictors of treatment transition.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003e We retrospectively reviewed 89 patients with ISUP 1 PCa managed with AS between 2010 and 2024. Inclusion criteria were PSA\u0026thinsp;\u0026lt;\u0026thinsp;10 ng/mL and \u0026le;\u0026thinsp;2 positive biopsy cores with \u0026le;\u0026thinsp;50% tumor involvement per core. Patients underwent regular PSA testing, mpMRI, and risk-adapted biopsies. Outcomes included treatment conversion, progression predictors, and the role of mpMRI.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eMedian follow-up was 52.8 months. PSA was monitored at a median interval of 4.8 months, and mpMRI was performed every 15.7 months (median). At diagnosis, 68.5% underwent mpMRI, with PIRADS 4 as the most frequent finding. During AS, 66.3% underwent at least one re-biopsy, most commonly triggered by PSA progression (73%). Treatment was initiated in 37.1% after a median of 37.9 months due to PSA progression (54.5%), mpMRI changes (21.2%), combined PSA/mpMRI findings (6.1%), histological upgrading (9.1%), or patient preference (3%). Treatments included radical prostatectomy, EBRT or LDR brachytherapy. Among these patients, no PSA persistence was observed; biochemical recurrence occurred in 6.1%, metastases in 4.0%, and overall mortality in 4.5%, with no PCa-specific deaths.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eA structured, risk-adapted AS protocol using PSA kinetics and mpMRI enabled personalized management and timely detection of progression. These findings support the standardization of AS protocols, which should be validated in larger cohorts.\u003c/p\u003e","manuscriptTitle":"Real-World Monitoring Strategies and Predictors guiding the Transition from Active Surveillance to Treatment in ISUP 1 Prostate Cancer","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-06 15:32:37","doi":"10.21203/rs.3.rs-6495543/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"5a7ee6c7-e5ff-43d3-a1c2-c703e9de0851","owner":[],"postedDate":"May 6th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-06-11T07:24:06+00:00","versionOfRecord":[],"versionCreatedAt":"2025-05-06 15:32:37","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6495543","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6495543","identity":"rs-6495543","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}