Prior studies have concentrated exclusively on how different prostate-specific antigen (PSA) levels affect the prognosis of high-grade prostate cancer (PCa), often overlooking the prognosis of low-grade PCa.

The present cohort study included individuals diagnosed with PCa from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2021. The all-cause mortality (ACM) and prostate cancer-specific mortality (PCSM) for each treatment group was calculated stratified by the four PSA levels (≤ 4.0, 4.1-10.0, 10.1-20.0, and > 20.0 ng/mL). Fine and Gray competing-risks analyses were conducted to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). Cox proportional hazards regression analyses using PSA as a continuous variable with restricted cubic splines (RCS) were conducted to allow for potential nonlinear relationships.

This study encompassed 416,825 male patients diagnosed with PCa. Compared to individuals with PSA value between 4.1 and 10.0 ng/mL, a significant association between low levels of PSA (≤ 4.0 ng/mL) and an increased risk of ACM (AHR = 1.15, 95% CI: 1.12-1.19; p < 0.001) and PCSM (AHR = 1.49, 95% CI: 1.38-1.61; p < 0.001) was observed. Additionally, the increased risk of ACM (AHR = 1.35, 95% CI: 1.29-1.40; p < 0.001) and PCSM (AHR = 1.84, 95% CI: 1.67-2.02; p < 0.001) are more pronounced within the first 5 years post-diagnosis. In most subgroups, similar results were observed. The RCS curves further corroborated the correlation between PSA value and the risk of mortality.

Low PSA levels are notably linked to a heightened risk for both ACM and PCSM, irrespective of the grade of PCa being high or low. There is a need to initiate new studies that tackle novel diagnostics and therapeutics.

To investigate the safety and cancer control of a novel bioabsorbable, low-dose rate brachytherapy device, CivaSheet® (CivaTech Oncology Inc., Durham, NC, USA), in combination with radical prostatectomy (RP) with or without adjuvant external beam radiation therapy (EBRT) for the management of prostate cancer (PCa).

This is an initial, single-centre experience, two-dose level, two-stage study conducted on patients with intermediate- and high-risk PCa. The CivaSheet was implanted during RP, followed by adjuvant EBRT in patients with adverse pathological features. Toxicities and peri- and postoperative complications were assessed. Biochemical recurrence (BCR) at the 6-month follow-up after EBRT was also evaluated.

Six patients were enrolled, with a median (range) age of 56 (53-71) years. No intraoperative complications occurred. No dose-limiting toxicities were observed at a maximum tested dose of 75 Gy. BCR occurred in one patient at 6 months, while another patient had residual disease and metastasis at 6 months. All patients reported having postoperative erectile dysfunction and one patient experienced urinary incontinence after EBRT.

This study demonstrated the feasibility and safety of CivaSheet combined with RP and adjuvant EBRT for high-risk PCa. The short-term toxicity profile was well-tolerated, supporting further prospective evaluation with clinical trials.

This study aimed to evaluate the risk classification system using the detailed positive surgical margin (PSM) status to predict biochemical recurrence (BCR) after robot-assisted radical prostatectomy (RARP).

We retrospectively analyzed 427 patients who underwent RARP between January 2016 and March 2020. We investigated risk factors for BCR using univariate and multivariate Cox proportional hazard regression models. The biochemical recurrence-free survival (BRFS) rate was assessed using the Kaplan-Meier method.

The median follow-up period was 43.4 months and 99 patients developed BCR. In the multivariate analysis, maximum PSM length > 5.0 mm and the International Society of Urological Pathology grade group (ISUP GG) at the PSM ≥3 were predictive factors for BCR in patients with a PSM. In the multivariate analysis, these factors were also independent predictive factors in the overall study population, including patients without a PSM. We classified the patients into four groups using these factors and found that the 1-year BRFS rates in the negative surgical margin (NSM) group, low-risk group (PSM and neither factor), intermediate-risk group (either factor), and high-risk group (both factors) were 94.9%, 94.5%, 83.1%, and 52.9%, respectively. The low-risk group showed similar BRFS to the NSM group (p = 0.985), while the high-risk group had significantly worse BRFS than the other groups (p < 0.001).

Maximum PSM length > 5.0 mm and ISUP GG at the PSM ≥3 were independent predictive factors for BCR after RARP. Risk classification for BCR using these factors is considered to be useful and might help urologists decide on additional treatment after RARP.

Prostrate-specific membrane antigen positron emission tomography (PSMA-PET) imaging has led to an increase in identifiable small volume metastatic disease in prostate adenocarcinoma. There is clinical equipoise in how to treat these using radiotherapy regimens. The aim of this study is to determine an adequate dosing regimen for small volume lymphatic metastases in prostate adenocarcinoma.

The authors first estimated the cell count of small volume metastases in prostate adenocarcinoma and then used a Poisson distribution-based estimation of the tumour control probability distribution, the required doses for 95% and 99% probabilities of tumour sterilisation were calculated using the linear quadratic formula.

Lymph node metastases of 3, 5, and 10 mm diameter were estimated to harbour 1.4, 6.5, and 52.3 million clonogens, respectively. When attempting for a 95% tumour control probability, estimated BEDs of 116.5, 127.0, and 141.1Gy were required. This translated to doses of 26.0, 27.3, and 29.0Gy in 5 fraction regimens. When attempting for a 99% tumour control probability, estimated biological effective doses (BEDs) of 127.6, 138.1, and 152.2 Gy were required. This translated to doses of 27.4, 28.6, and 30.2 Gy in 5 fraction regimens.

In prostate cancers with small-volume metastatic disease, doses can be adjusted according to tumour size without likely to compromise tumour control. This would have positive implications on radiotherapy planning and possibly lead to decreased risks of toxicity in scenarios where planning difficulty is encountered. Clinical evaluation of efficacy and safety for these dose regimens is warranted.

Approximately 15% of patients with localized prostate cancer are at high risk for disease recurrence. Many clinical trials have evaluated the impact of neoadjuvant therapy before radical prostatectomy with mixed results (NCT00321698).

This phase I/II clinical trial evaluated the tolerability and preliminary efficacy of neoadjuvant radiation therapy and docetaxel before prostatectomy in 25 men with high-risk prostate cancer. The treatment regimen included 45 Gy radiotherapy in 25 fractions to the prostate and seminal vesicles over 5 weeks, along with weekly dose-escalated docetaxel up to 30 mg/m², followed by prostatectomy and bilateral lymph node dissection. The primary endpoint was the rate of pathologic complete response (pCR). Secondary endpoints included adverse events, symptom and quality of life measures, and prostate-specific antigen metrics.

All 25 patients completed the planned treatment. The primary endpoint of pCR was not achieved. Lymphopenia was the most common grade 3 or higher toxicity, with no grade 3 or higher genitourinary or gastrointestinal toxicities observed. With a median follow-up of 11.6 years, the 10-year biochemical recurrence-free survival was 60%, and distant metastasis-free survival was 80%. Prostate cancer-specific survival and overall survival at 10 years were 84% and 60%, respectively.

Although pCR was not met, the treatment demonstrated a modest toxicity profile and reasonable long-term outcomes, suggesting feasibility and safety. Further studies are needed to optimize endpoints and assess the efficacy of neoadjuvant treatments compared with standard approaches in high-risk prostate cancer patients.

Decipher is a tissue-based genomic classifier (GC) developed and validated in the post-radical prostatectomy (RP) setting as a predictor of metastasis. We conducted a prospective randomized controlled cluster-crossover trial assessing the use of Decipher to determine its impact on adjuvant treatment after RP.

Eligible patients had undergone RP within 9 mo of enrollment, had pT3-4 disease and/or positive surgical margins, and prostate-specific antigen <0.1 ng/ml. Centers were randomized to a sequence of 3-mo periods of either GC-informed care or usual care (UC). Cancer of the Prostate Risk Assessment Postsurgical (CAPRA-S) recurrence risk scores were provided to treating physicians and patients in all periods.

Impact of GC test results on adjuvant treatment were compared with UC alone. Longitudinal patient-reported urinary and sexual function was assessed. A total of 175 patients were enrolled in 27 periods with GC and 163 in 28 periods with UC. At 18 mo after RP, an average patient in the GC arm received adjuvant treatment 9.7% of the time compared with 8.7% for an average individual in the UC arm (0.99% mean difference, 95% confidence interval [CI] -7.6%, 9.6%, p = 0.8). While controlling for CAPRA-S score, higher GC scores tended to result in an increased likelihood of adjuvant treatment that was not statistically significant (odds ratio [OR] = 1.35 per 0.1 increase in GC score, 95% CI 0.98-1.85, p = 0.066). Using the GC risk groups, reflecting clinical use, a high GC risk was associated with significantly higher odds of receiving adjuvant treatment (OR = 6.9, 95% CI 1.8, 26, p = 0.005) compared with a low GC score, adjusted for CAPRA-S score. There were no differences in patient-reported urinary and sexual function between the study arms. As oncologic outcomes are immature, the present data cannot address whether GC testing provides any cancer control benefit.

GC testing impacts adjuvant therapy administration when viewed through the risk categories presented in the patient report; however, these data do not provide specific support for GC testing in the adjuvant treatment setting.

To evaluate the feasibility and tolerance of ultra-hypofractionated SABR (stereotactic ablative radiation therapy) protocol following radical prostatectomy.

We included patients undergoing adjuvant or salvage SABR between April 2019 and April 2023 targeting the surgical bed and pelvic lymph nodes up to a total dose of 36.25 Gy (7.25 Gy/fraction) and 26 Gy (5.2 Gy/fraction), respectively, in 5 fractions on alternate days with an urethra sparing protocol. Acute and late adverse effects were assessed using the CTCAE v5.0. Pearson's chi-square test for categorical variables was used to compare characteristics and possible associations among different subgroups.

Adjuvant radiation therapy (ART) was administered to 40 high-risk patients (detectable post-surgery PSA, Grade Group 4/5, nodal involvement, R1/R2 resection margin), while salvage radiotherapy (SRT) was delivered to 60 patients with rising PSA levels post-undetectable values. Elective nodal irradiation was performed in 57 patients, with 11 additional patients receiving a simultaneous integrated boost (total dose: 40 Gy in 5 fractions) for macroscopic nodal disease. Twenty-four high-risk patients underwent 24-months androgen deprivation therapy (ADT). Treatment was well-tolerated with minimal toxicity. The maximum grade of SABR-related toxicity observed was grade 3. Acute gastrointestinal (GI) toxicity included seven cases of grade 2 and one of grade 3, while acute genitourinary (GU) events were limited to grade 2 in eight patients. Early-late toxicity included two cases of grade 3 and seven of grade 2 for GI, and 11 cases of grade 2 for GU. No toxicity above grade 3 was reported. With a median follow-up of 24 months (6-60 months), 14 patients experienced disease recurrence.

Ultra-hypofractionated adjuvant/salvage SABR appears feasible and safe. Longer follow-up is needed to validate observed outcomes.

Intraductal carcinoma of the prostate cancer (IDC-P), as a specific pathological type in prostate cancer which usually implies a poor prognosis. IDC-P morphology can be divided into two subtypes: Pattern 1, sieve like or loose cribriform structures; Pattern 2, solid or dense cribriform structures. The purpose of the study is to identify the impact of IDC-P and its subtypes on the prognosis of patients undergoing post-operative radiotherapy (PORT) after radical prostatectomy (RP) due to localized prostate cancer(PCa).

We performed a retrospective study of patients with localized PCa treated by RP followed by PORT or not. Patients with localized PCa who underwent RP from August 2013 to December 2020 were included in this study.

post-operative PSA dropped to less than 0.1 ng/ml after RP, had at least 1 poor prognostic risk factor (including high Gleason's grouping; positive surgical margins; seminal vesicle invasion; extraprostatic extension; and lympho-vascular invasion), and were eligible for adjuvant radiotherapy.; In this study, patients who underwent salvage radiotherapy after RP due to biochemical recurrence (two consecutive PSA > 0.2 ng/ml) were also included, but not patients with persistent postoperative PSA > 0.1 ng/ml.

patients using other types of therapy prior to biochemical recurrence. Screening cases with pathological results of intraductal carcinoma, subtyping was completed by a pathologist, grouped by intraductal carcinoma (+/-; pattern 1/ 2) and treatment regimen (RP + PORT / RP only), Kaplan-Meier curves were plotted based on the time to biochemical recurrence-free and overall survival of the patients, and Cox regression analyses were performed. Finally, based on the results of Cox regression analysis, we initially predicted the probability of biochemical recurrence and death of the patients by plotting the nomogram.

A total of 139 patients were included in this study with a median follow-up of 61.5 months. K-M curves showed that patients with "IDC-P (+) RP only" had the worst prognosis; patients with IDC-P could have a survival benefit after receiving PORT; whereas patients with non-intraductal carcinoma had a better prognosis than the above patients with or without PORT. In addition, patients with IDC-P(+) pattern 2 were more likely to experience biochemical recurrence and death. Multivariate Cox regression analysis showed that pattern 2 was a risk factor for biochemical recurrence and death. Other BCR-related risk factors in the research: Gleason grading group 5 (HR = 3.343, 95% CI: 1.616-6.916, P = 0.001), PM (HR = 2.124, 95% CI: 1.044-4.320,P = 0.038) and PORT (HR = 0.266, 95%CI: 0.109-0.647, P = 0.004). Other OS-related risk factors in the research: Grading group 5 (HR = 3.642, 95%CI:1.475-8.991, P = 0.005), SVI (HR = 2.522, 95% CI: 1.118-5.691, P = 0.026) and PORT (HR = 0.319, 95%CI: 0.107-0.949, P = 0.040).

Patients suffering from localized prostate cancer with IDC-P(+), especially IDC-P pattern 2, are more susceptible to biochemical recurrence and death after radical prostatectomy. While postoperative radiotherapy can alleviate the negative prognostic impact from IDC-P. It is implied that IDC-P can also be an indicator to be considered in PORT decision making to some extent.

There are concerns that radiotherapy for prostate cancer influences health-related quality of life in the long term. Furthermore, it is unclear whether postoperative radiotherapy is associated with a different quality of life due to a higher treatment burden compared to patients having received definitive radiotherapy for prostate cancer. This study enrolled 247 patients with localized or locally advanced prostate cancer who received external radiotherapy between 2011 and 2021. Health-related quality of life was assessed at a median of 63.6 months after radiotherapy using the European Organization for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-C30) with 145 patients returning questionnaires (response rate, 58.7%). Four patients treated with adjuvant radiotherapy were excluded due to the small number, resulting in 141 participants who received salvage radiotherapy (70 men) or definitive radiotherapy (71 men). The study compared the quality of life with age- and sex-matched German normative data. Patients completed the questionnaires after a median time of 60.3 and 65.2 months after salvage and definitive radiotherapy. The median patient age was higher in the definitive than in the salvage radiotherapy group (at radiotherapy, 72 vs. 69 years; at the survey, 79 vs. 75 years). Global health status, functional scales (physical, role, emotional, cognitive, and social), and symptom scales were not different between cancer patients of the same age group treated with salvage and definitive radiotherapy. The comparison with age- and sex-matched normative data revealed that salvage and definitive radiotherapy did not impair the global health status in patients of any age group. Physical functioning in patients < 70 years was significantly better in salvage and definitive radiotherapy groups compared to normative data while showing clinical relevance. Yet, social functioning was significantly lower in patients ≥ 70 years of the salvage radiotherapy group compared to normative data, while this difference lacked clinical significance. Regardless of the type of radiotherapy applied, cancer patients had no statistically or clinically relevant higher symptom burden compared to normative data. Quality of life was not clinically relevant influenced by radiotherapy, regardless of whether patients received salvage or definitive radiotherapy. Yet, longitudinal measurements of quality of life after radiotherapy are required to detect fluctuations in quality of life.

Radical prostatectomy (RP) is one possible curative treatment for localized prostate cancer. Despite that, up to 40% of patients will later relapse. Currently, post-operative radiotherapy (PORT) courses deliver 1.8-2 Gy daily to reach a total dose ranging between 64 and 74 Gy, completed in 7-8 weeks. Several articles reported encouraging data in terms of the effectiveness and the related toxicities using hypofractionation schedules. The objective of the present systematic review was to evaluate the clinical outcomes and toxicity of the use of hypofractionation in adjuvant/salvage prostate cancer treatments.

Medline was searched via PubMed and Scopus from inception to July 2024 to retrieve studies on hypofractionation in adjuvant/salvage prostate cancer treatments. This study was conducted under PRISMA guidelines.

A total of 139 articles were identified from the initial search. Subsequently, the 139 studies were reviewed by title and abstract. Ninety-five studies were excluded due to being either abstracts or articles not available in English. In the second step, the full texts of 44 studies were reviewed. Eleven studies were excluded for being reviews, study protocols, or focused on SBRT treatments. Finally, 33 studies were included in our analysis, with a total number of 4269 patients. Of the 33 selected studies, 20 were retrospective trials and 11 were phase I/II prospective trials, while 2 studies were prospective phase III trials. The follow-up ranged from 18 to 217 months. Failure-free survival, for those with the longer follow-up, ranged between 85% and 91% at 3 years, 47 and 78.6% at 5 years and 51.5% at 10 years. Genitourinary (GU) and gastrointestinal acute toxicity was mild to moderate with similar rates across the normofractionated and hypofractionated groups. Acute grade-3 GU toxicity events were unusual, occurring in less than 4% of the cases overall.

The present study is the first systematic review of the literature that includes the first two randomized phase III studies published in the literature. Hypofractionated treatment has been shown to be safe, effective, with moderate toxicity and not inferior to conventional RT, with good biochemical control rates.

To construct and externally calibrate a predictive model for early biochemical recurrence (BCR) after radical prostatectomy (RP) incorporating clinical and modern imaging characteristics of the primary tumour.

Patients who underwent RP following multiparametric magnetic resonance imaging, prostate biopsy and prostate-specific membrane antigen-positron emission tomography/computed tomography (PSMA-PET/CT), from two centres in Australia and the Netherlands. The primary outcome was biochemical recurrence-free survival (BRFS), where BCR was defined as a rising PSA level of ≥0.2 ng/mL or initiation of postoperative treatment per clinician discretion. Proportional hazards models to predict time to event were developed in the Australian sample using relevant pre- and post-surgical parameters and primary tumour maximum standardised uptake value (SUVmax) on diagnostic PSMA-PET/CT. Calibration was assessed in an external dataset from the Netherlands with the same inclusion criteria.

Data from 846 patients were used to develop the models. Tumour SUVmax was associated with worse predicted 3-year BRFS for both pre- and post-surgical models. SUVmax change from 4 to 16 lessened the predicted 3-year BRFS from 66% to 42% for a patient aged 65 years with typical pre-surgical parameters (PSA level 8 ng/mL, Prostate Imaging-Reporting and Data System score 4/5 and biopsy Gleason score ≥4 + 5). Considering post-surgical variables, a patient with the same age and PSA level but pathological stage pT3a, RP Gleason score ≥4 + 5 and negative margins, SUVmax change from 4 to 16 lessened the predicted 3-year BRFS from 76% to 61%. Calibration on an external sample (n = 464) showed reasonable performance; however, a tendency to overestimate survival in patients with good prognostic factors was observed.

Tumour SUVmax on diagnostic PSMA-PET/CT has utility additional to commonly recognised variables for prediction of BRFS after RP.

Early salvage radiotherapy (SRT) is the standard of care for biochemical recurrence post-prostatectomy but outcomes are heterogeneous.

To develop a risk scoring system based on relevant standard-of-care clinico-pathological prognostic factors for patients treated with SRT with and without hormonal therapy (HT).

The Intermediate Clinical Endpoints in Cancer of the Prostate (ICECaP) database included three randomized trials (Individual patients' data from 1647 subjects) assessing SRT (GETUG-AFU-16; NRG/RTOG-9601, and a subset of EORTC-22911).

Outcomes were clinical progression (CP). metastasis free-survival (MFS) and overall survival (OS). Clinico-pathological factors, including pathological Gleason Score (GS), PSA at SRT start, margin status, persistent PSA post-RP and time from RP to SRT were evaluated by multivariable models stratified by type of treatment.

On multivariable analysis PSA ≥ 0.5 ng/mL at SRT start, GS ≥ 8 and negative margin status were the three strongest prognostic factors. Three prognostic groups defined by number of these risk features (high risk: 2 or 3; intermediate risk: 1 and low risk: 0) were strongly associated with OS, MFS and CP outcomes with SRT alone or with HT. This prognostic group definition was also relevant for patients with persistent PSA post RP and for patients treated < 1 year from RP to SRT and with and without HT.

A risk score for patients receiving SRT with or without HT, using three standard-of-care clinico-pathological risk factors provides refined prognostic information for individual patient counselling.

By using a composite score of pathology grading (Gleason Score), PSA at start of salvage radiation and margin status data, physicians can provide patients with more refined information on the risk of a second relapse after receiving radiation to the prostate bed after a prostatectomy for a rising or persistent PSA, both with and without hormonal therapy.

For biochemical recurrence following radical prostatectomy for prostate cancer, treatments such as radiation therapy and androgen deprivation therapy are administered. To diagnose postoperative recurrence as early as possible and to intervene with treatment at the appropriate time, it is essential to accurately predict recurrence after radical prostatectomy. However, postoperative recurrence involves numerous patient-related factors, making its prediction challenging. The purpose of this study is to accurately predict the timing of biochemical recurrence after radical prostatectomy and to analyze the risk factors for follow-up of high-risk patients and early detection of recurrence.

We utilized the machine learning survival analysis model called the Random Survival Forest utilizing the 58 clinical factors from 548 patients who underwent radical prostatectomy at Chiba University Hospital. To visualize prognostic factors and assess accuracy of the time course probability, we employed SurvSHAP(t) and time-dependent Area Under Cureve(AUC).

The time-dependent AUC of RSF was 0.785, which outperformed the Cox proportional hazards model (0.704), the Cancer of the Prostate Risk Assessment (CAPRA) score (0.710), and the D'Amico score (0.658). The key prognostic factors for early recurrence were Gleason score(GS), Seminal vesicle invasion(SV), and PSA. The contribution of PSA to recurrence decreases after the first year, while SV and GS increase over time.

Our prognostic model analyzed the time-dependent relationship between the timing of recurrence and prognostic factors. Our study achieved personalized prognosis analysis and its rationale after radical prostatectomy by employing machine learning prognostic model. This prognostic model contributes to the early detection of recurrence by enabling clinicians to conduct appropriate follow-ups for high-risk patients.

The Oncology Committee of the French Urology Association is proposing updated recommendations for the management of recurrent and/or metastatic prostate cancer (PCa).

A systematic review of the literature from 2022 to 2024 was conducted by the CCAFU on the therapeutic management of recurrent PCa following local or metastatic treatment, assessing the references based on their level of evidence.

Molecular imaging is the standard approach for assessing recurrence after local treatment and should not delay early salvage treatment. Androgen deprivation therapy (ADT) is the primary treatment option for metastatic PCa. Intensification of ADT, now cononsidered standard care for metastatic PCa, involves incorporating at least one new-generation hormone therapy (ARPI). For patients with high-volume metastatic disease at diagnosis, adding docetaxel to ADT+ARPI may be considered for eligible patients. In castration-resistant PCa (CRPC) patients, poly(ADP) ribose polymerase (PARP) inhibitors and PSMA radioligand therapy are new treatment options. The combination and sequencing of treatmentsare influenced by several factors, including patient and disease characteristics, prior therapies, genomic status, and molecular imaging findings.

This update of French recommendations should help to improve the management recurrent or metastatic PCa patients.

The association between radiotherapy (RT) timing after radical prostatectomy and long-term patient-reported health-related quality of life (HRQOL) in men with prostate cancer is unknown.

To measure long-term HRQOL in men with prostate cancer up to 15 years after prostatectomy with or without RT and examine whether early vs late postprostatectomy RT is associated with differences in sexual, urinary, and bowel HRQOL.

A prospective, multicenter, longitudinal cohort analysis using HRQOL data from the PROST-QA (2003-2006) and RP2 consortium (2010-2013) studies was conducted. Men with localized prostate cancer undergoing radical prostatectomy were included. Data were analyzed between May 8, 2023, and March 1, 2024. The study was conducted in 12 high-volume academic medical centers in the US.

Men were stratified based on receipt and timing of postprostatectomy RT: prostatectomy only, early RT (<12 months), and late RT (≥12 months).

Longitudinal sexual, incontinence, urinary irritation, bowel, and hormonal/vitality HRQOL were measured via the Expanded Prostate Cancer Index Composite at baseline; months 2, 6, and 12; and annually thereafter. Treatment groups were compared using multivariable linear mixed-effects models of change in longitudinal domain scores. Pad use for incontinence was measured longitudinally among men receiving postprostatectomy RT.

A total of 1203 men were included in the study: prostatectomy only (n = 1082), early RT (n = 57), and late RT (n = 64). Median age for the entire cohort was 60.5 (range, 38.8-79.7) years, and 1075 men (92.0%) were White. Median follow-up was 85.6 (IQR, 35.8-117.2) months. Compared with men receiving prostatectomy alone, those receiving postprostatectomy RT had significantly greater decreases in sexual, incontinence, and urinary irritation HRQOL. However, timing of postprostatectomy RT, specifically early vs late, was not associated with a long-term decrease in any HRQOL domain. There was evidence of improved recovery of sexual, continence, and urinary irritation scores among men receiving early RT compared with those receiving late RT after prostatectomy. Before the start of postprostatectomy RT, 39.3% of men in the early RT cohort and 73.4% of men in the late RT cohort were pad-free. By the sixth visit post-RT, 67.4% in the early RT cohort and 47.6% in the late RT cohort were pad-free.

In this multicenter, prospective analysis, postprostatectomy RT appeared to be negatively associated with long-term HRQOL across all domains. However, receipt of early vs late postprostatectomy RT may result in similar long-term HRQOL outcomes.

Early salvage radiotherapy is indicated for patients with biochemical recurrence after radical prostatectomy. However, for various reasons, certain patients do not benefit from this treatment (OBS) or only at a late stage (LSR). There are few studies on this subject and none on a "high-risk" population, such as patients of African descent. Our objective was to estimate the metastasis-free (MFS) and overall survival (OS) of patients who did not receive salvage radiotherapy, and to identify risk factors of disease progression.

This was a single-center retrospective study that included 154 patients, 99 in the OBS group and 55 in the LSR group. All were treated by total prostatectomy for localized prostate cancer between January 2000 and December 2020 and none received early salvage radiotherapy after biochemical recurrence.

Baseline characteristics were similar between groups, except for the time to biochemical recurrence. The median follow-up was 10.0 and 11.8 years for the OBS and LSR groups, respectively. The median time from surgery to LSR was 5.1 years. The two groups did not show a significant difference in MFS: 90.6% at 10 years for the OBS group and 93.3% for the LSR group. The median MFS was 19.8 and 19.6 years for the OBS and LSR groups respectively. OS for the OBS group was significantly higher than that for the LSR group (HR: 2.14 [1.07-4.29]; p = 0.03), with 10-year OS of 95.9% for the OBS group and 76.1% for the LSR group. Median OS was 16 and 15.6 years for the OBS and LSR groups, respectively.

In this study, we observed satisfactory metastasis-free and OS rates relative to those reported in the scientific literature. The challenge is not to question the benefit of early salvage radiotherapy, but to improve the identification of patients at risk of progression through the development of molecular and genomic tests for more highly personalized medicine.

Delays in the work-up and definitive management of patients with prostate cancer are common, with logistics of additional work-up after initial prostate biopsy, specialist referrals, and psychological reasons being the most common causes of delays. During the COVID-19 pandemic and the subsequent surges, timing of definitive care delivery with surgery or radiotherapy has become a topic of significant concern for patients with prostate cancer and their providers alike. In response, recommendations for the timing of definitive management of prostate cancer with radiotherapy and radical prostatectomy were published but without a detailed rationale for these recommendations. While the COVID-19 pandemic is behind us, patients are always asking the question: "When should I start radiation or undergo surgery?" In the absence of level I evidence specifically addressing this question, we will hereby present a narrative review to summarize the available data on the effect of treatment delays on oncologic outcomes for patients with localized prostate cancer from prospective and retrospective studies.

The role of elective pelvic nodal irradiation in salvage radiotherapy (sRT) remains controversial. Utilizing 18F-DCFPyL PET/CT, this study aimed to investigate differences in disease distribution after whole pelvic (WPRT) or prostate bed (PBRT) radiotherapy and to identify risk factors for pelvic lymph node (LN) relapse.

This retrospective study included patients with PSA > 0.1 ng/mL post-radical prostatectomy (RP) or post-RP and sRT who underwent 18F-DCFPyL PET/CT. Disease distribution on 18F-DCFPyL PET/CT after sRT was compared using Chi-square tests. Risk factors were tested for association with pelvic LN relapse after RP and salvage PBRT using logistic regression.

979 18F-DCFPyL PET/CTs performed at our institution between 1/1/2022 - 3/24/2023 were analyzed. There were 246 patients meeting criteria, of which 84 received salvage RT after RP (post-salvage RT group) and 162 received only RP (post-RP group). Salvage PBRT patients (n = 58) had frequent pelvic nodal (53.6%) and nodal-only (42.6%) relapse. Salvage WPRT patients (n = 26) had comparatively lower rates of pelvic nodal (16.7%, p = 0.002) and nodal-only (19.2%, p = 0.04) relapse. The proportion of distant metastases did not differ between the two groups. Multiple patient characteristics, including ISUP grade and seminal vesicle invasion, were associated with pelvic LN disease in the post-RP group.

At PSA persistence or progression, salvage WPRT resulted in lower rates of nodal involvement than salvage PBRT, but did not reduce distant metastases. Certain risk factors increase the likelihood of pelvic LN relapse after RP and can help inform salvage RT field selection.

The goal is to describe the evolution of radiation therapy (RT) utilization in the management of localized and metastatic prostate cancer.

Long term data for a variety of hypofractionated definitive RT dose-fractionation schemes has matured, allowing patients and providers many standard-of-care options to choose from. Post-prostatectomy, adjuvant RT has largely been replaced by an early salvage approach. Multiparametric MRI and PSMA PET have enabled increasingly targeted RT delivery to the prostate and oligometastatic tumors. Areas of active investigation include determining the value of proton beam therapy and perirectal spacers, and optimally incorporate genomic tumor profiling and next generation hormonal therapies with RT in the curative setting. The use of radiation therapy to treat prostate cancer is rapidly evolving. In the coming years, there will be continued improvements in a variety of areas to enhance the value of RT in multidisciplinary prostate cancer management.

Adjuvant therapy is associated with improved pancreatic cancer survival after neoadjuvant chemotherapy and surgery. However, whether adjuvant treatment should include radiotherapy is unclear in this setting.

This study queried the National Cancer Database for pancreatic adenocarcinoma patients who underwent curative resection after multiagent neoadjuvant chemotherapy between 2010 and 2019 and received adjuvant treatment. Adjuvant chemotherapy plus radiotherapy (external beam, 45-50.4 gray) was compared with adjuvant chemotherapy alone. Uni- and multivariable Cox regression was used to assess survival associations. Analyses were repeated in a propensity score-matched subgroup.

Of 1983 patients who received adjuvant treatment after multiagent neoadjuvant chemotherapy and resection, 1502 (75.7%) received adjuvant chemotherapy alone and 481 (24.3%) received concomitant adjuvant radiotherapy (chemoradiotherapy). The patients treated with adjuvant chemoradiotherapy were younger, were treated at non-academic facilities more often, and had higher rates of lymph node metastasis (ypN1-2), positive resection margins (R1), and lymphovascular invasion (LVI+). The median survival was shorter for the chemoradiotherapy-treated patients according to the unadjusted analysis (26.8 vs 33.2 months; p = 0.0017). After adjustment for confounders, chemoradiotherapy was associated with better outcomes in the multivariable model (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.61-0.93; p = 0.008). The association between chemoradiotherapy and improved outcomes was stronger for the patients with grade III tumors (HR, 0.53; 95% CI, 0.37-0.74) or LVI+ tumors (HR, 0.58; 95% CI, 0.44-0.75). In a subgroup of 396 propensity-matched patients, chemoradiotherapy was associated with a survival benefit only for the patients with LVI+ or grade III tumors.

After multiagent neoadjuvant chemotherapy and resection for pancreatic cancer, additional adjuvant chemoradiotherapy versus adjuvant chemotherapy alone is associated with improved survival for patients with LVI+ or grade III tumors.

Background and purpose: Proton therapy has been shown to provide dosimetric benefits in comparison with IMRT when treating prostate cancer with whole pelvis radiation; however, the optimal proton beam arrangement has yet to be established. The aim of this study was to evaluate three different intensity-modulated proton therapy (IMPT) beam arrangements when treating the prostate bed and pelvis in the postoperative setting. Materials and Methods: Twenty-three post-prostatectomy patients were planned using three different beam arrangements: two-field (IMPT2B) (opposed laterals), three-field (IMPT3B) (opposed laterals inferiorly matched to a posterior-anterior beam superiorly), and four-field (IMPT4B) (opposed laterals inferiorly matched to two posterior oblique beams superiorly) arrangements. The prescription was 50 Gy radiobiological equivalent (GyE) to the pelvis and 70 GyE to the prostate bed. Comparisons were made using paired two-sided Wilcoxon signed-rank tests. Results: CTV coverages were met for all IMPT plans, with 99% of CTVs receiving ≥ 100% of prescription doses. All organ at risk (OAR) objectives were met with IMPT3B and IMPT4B plans, while several rectum objectives were exceeded by IMPT2B plans. IMPT4B provided the lowest doses to OARs for the majority of analyzed outcomes, with significantly lower doses than IMPT2B +/- IMPT3B for bladder V30-V50 and mean dose; bowel V15-V45 and mean dose; sigmoid maximum dose; rectum V40-V72.1, maximum dose, and mean dose; femoral head V37-40 and maximum dose; bone V40 and mean dose; penile bulb mean dose; and skin maximum dose. Conclusion: This study is the first to compare proton beam arrangements when treating the prostate bed and pelvis. four-field plans provided better sparing of the bladder, bowel, and rectum than 2- and three-field plans. The data presented herein may help inform the future delivery of whole pelvis IMPT for prostate cancer.

The optimal timing of radiotherapy (RT) after radical prostatectomy for prostate cancer has been uncertain. RADICALS-RT compared efficacy and safety of adjuvant RT versus an observation policy with salvage RT for prostate-specific antigen (PSA) failure.

RADICALS-RT was a randomised controlled trial enrolling patients with ≥1 risk factor (pT3/4, Gleason 7-10, positive margins, preoperative PSA≥10 ng/ml) for recurrence after radical prostatectomy. Patients were randomised 1:1 to adjuvant RT ('Adjuvant-RT') or an observation policy with salvage RT for PSA failure ('Salvage-RT') defined as PSA≥0.1 ng/ml or three consecutive rises. Stratification factors were Gleason score, margin status, planned RT schedule (52.5 Gy/20 fractions or 66 Gy/33 fractions) and treatment centre. The primary outcome measure was freedom-from-distant-metastasis (FFDM), designed with 80% power to detect an improvement from 90% with Salvage-RT (control) to 95% at 10 years with Adjuvant-RT. Secondary outcome measures were biochemical progression-free survival, freedom from non-protocol hormone therapy, safety and patient-reported outcomes. Standard survival analysis methods were used; hazard ratio (HR)<1 favours Adjuvant-RT.

Between October 2007 and December 2016, 1396 participants from UK, Denmark, Canada and Ireland were randomised: 699 Salvage-RT, 697 Adjuvant-RT. Allocated groups were balanced with a median age of 65 years. Ninety-three percent (649/697) Adjuvant-RT reported RT within 6 months after randomisation; 39% (270/699) Salvage-RT reported RT during follow-up. Median follow-up was 7.8 years. With 80 distant metastasis events, 10-year FFDM was 93% for Adjuvant-RT and 90% for Salvage-RT: HR=0.68 [95% confidence interval (CI) 0.43-1.07, P=0.095]. Of 109 deaths, 17 were due to prostate cancer. Overall survival was not improved (HR=0.980, 95% CI 0.667-1.440, P=0.917). Adjuvant-RT reported worse urinary and faecal incontinence 1 year after randomisation (P=0.001); faecal incontinence remained significant after 10 years (P=0.017).

Long-term results from RADICALS-RT confirm adjuvant RT after radical prostatectomy increases the risk of urinary and bowel morbidity, but does not meaningfully improve disease control. An observation policy with salvage RT for PSA failure should be the current standard after radical prostatectomy.

RADICALS, RADICALS-RT, ISRCTN40814031, NCT00541047.

To evaluate effects of dose intensified salvage radiotherapy (sRT) on erectile function in biochemically recurrent prostate cancer (PC) after radical prostatectomy (RP).

Eligible patients had evidence of biochemical failure after RP and a PSA at randomization of ≤ 2 ng/ml. Erectile dysfunction (ED) was investigated as secondary endpoint within the multicentre randomized trial (February 2011 to April 2014) in patients receiving either 64 Gy or 70 Gy sRT. ED and quality of life (QoL) were assessed using CTCAE v4.0 and the EORTC QoL questionnaires C30 and PR25 at baseline and up to 5 years after sRT.

344 patients were evaluable. After RP 197 (57.3 %) patients had G0-2 ED while G3 ED was recorded in 147 (42.7 %) patients. Subsequently, sexual activity and functioning was impaired. 5 years after sRT, 101 (29.4 %) patients noted G0-2 ED. During follow-up, 44.2 % of patients with baseline G3 ED showed any improvement and 61.4 % of patients with baseline G0-2 ED showed worsening. Shorter time interval between RP and start of sRT (p = 0.007) and older age at randomization (p = 0.005) were significant predictors to more baseline ED and low sexual activity in the long-term. Age (p = 0.010) and RT technique (p = 0.031) had a significant impact on occurrence of long-term ED grade 3 and worse sexual functioning. During follow-up, no differences were found in erectile function, sexual activity, and sexual functioning between the 64 Gy and 70 Gy arm.

ED after RP is a known long-term side effect with significant impact on patients' QoL. ED was further affected by sRT, but dose intensification of sRT showed no significant impact on erectile function recovery or prevalence of de novo ED after sRT. Age, tumor stage, prostatectomy and RT-techniques, nerve-sparing and observation time were associated with long-term erectile function outcome.ClinicalTrials.gov. Identifier: NCT01272050.

Hypofractionated radiotherapy in the treatment of prostate cancer has been widely studied. However, in the postoperative setting it has been less explored. The objective of this prospective study is to evaluate the safety and efficacy of hypofractionated radiotherapy in postoperative prostate cancer.

A prospective study was designed to include patients with prostate cancer with an indication of postoperative radiotherapy as adjuvant or salvage. A hypofractionated radiotherapy scheme of 51 Gy in 17 fractions was performed with the possibility of treating the pelvis at a dose of 36 Gy in 12 fractions sequentially. Safety was evaluated based on acute and late toxicity [according to the Radiation Therapy Oncology Group (RTOG) scale and Common Terminology Criteria Adverse Events (CTCAE) v4.03], International Prognostic Scoring System (IPSS) over time, and quality of life.

From August 2020 to June 2022, 31 patients completed treatment and were included in this report. 35.5% of patients received elective treatment of the pelvic nodal areas. Most patients reported minimal or low acute toxicity, with an acute gastrointestinal (GI) and genitourinary (GU) grade 3 or greater toxicity of 3.2% and 0%, respectively. The evolution in time of the IPSS remained without significant differences (p = 0.42). With the exception of a significant improvement in the domains of hormonal and sexual symptoms of the Expanded Prostate Cancer Index Composite (EPIC) questionnaire, the rest of the domains [EPIC, European Organization for Research and Treatment of Cancer (EORTC) Core quality of life questionnaire (C-30) and Prostate Cancer module (PR-25)] were maintained without significant differences over time. With a follow-up of 15.4 months, late GI and GU grade 2 toxicity was reported greater than 0% and 9.6%, respectively.

Hypofractionated radiotherapy in postoperative prostate cancer appears to be safe with low reports of relevant acute or late toxicity. Further follow-up is required to confirm these results.

The protocol was approved by the accredited Medical Ethical Committee of Pontificia Universidad Católica de Chile. All participants accepted and wrote informed consent.

The increased risk of second cancer after prostate radiotherapy is a debated clinical concern. The objective of the study was to assess the risk of occurrence of second cancers after prostate radiation therapy based on the analysis the literature, and to identify potential factors explaining the discrepancies in results between studies.

A review of the literature was carried out, comparing the occurrence of second cancers in patients all presenting with prostate cancer, treated or not by radiation.

This review included 30 studies reporting the occurrence of second cancers in 2,112,000 patients treated or monitored for localized prostate cancer, including 1,111,000 by external radiation therapy and 103,000 by brachytherapy. Regarding external radiation therapy, the average follow-up was 7.3years. The majority of studies (80%) involving external radiation therapy, compared to no external radiation therapy, showed an increased risk of second cancers with a hazard ratio ranging from 1.13 to 4.9, depending on the duration of the follow-up. The median time to the occurrence of these second cancers after external radiotherapy ranged from 4 to 6years. An increased risk of second rectal and bladder cancer was observed in 52% and 85% of the studies, respectively. Considering a censoring period of more than 10 years after irradiation, 57% and 100% of the studies found an increased risk of rectal and bladder cancer, without any impact in overall survival. Studies of brachytherapy did not show an increased risk of second cancer. However, these comparative studies, most often old and retrospective, had many methodological biases.

Despite numerous methodological biases, prostate external radiation therapy appears associated with a moderate increase in the risk of second pelvic cancer, in particular bladder cancer, without impacting survival. Brachytherapy does not increase the risk of a second cancer.

Accurately detecting adverse pathology (AP) presence in prostate cancer patients is important for personalized clinical decision-making. Radiologists' assessment based on clinical characteristics showed poor performance for detecting AP presence.

To develop deep learning models for detecting AP presence, and to compare the performance of these models with those of a clinical model (CM) and radiologists' interpretation (RI).

Retrospective.

Totally, 616 men from six institutions who underwent radical prostatectomy, were divided into a training cohort (508 patients from five institutions) and an external validation cohort (108 patients from one institution).

T2-weighted imaging with a turbo spin echo sequence and diffusion-weighted imaging with a single-shot echo plane-imaging sequence at 3.0 T.

The reference standard for AP was histopathological extracapsular extension, seminal vesicle invasion, or positive surgical margins. A deep learning model based on the Swin-Transformer network (TransNet) was developed for detecting AP. An integrated model was also developed, which combined TransNet signature with clinical characteristics (TransCL). The clinical characteristics included biopsy Gleason grade group, Prostate Imaging Reporting and Data System scores, prostate-specific antigen, ADC value, and the lesion maximum cross-sectional diameter.

Model and radiologists' performance were assessed using area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. The Delong test was used to evaluate difference in AUC. P < 0.05 was considered significant.

The AUC of TransCL for detecting AP presence was 0.813 (95% CI, 0.726-0.882), which was higher than that of TransNet (0.791 [95% CI, 0.702-0.863], P = 0.429), and significantly higher than those of CM (0.749 [95% CI, 0.656-0.827]) and RI (0.664 [95% CI, 0.566-0.752]).

TransNet and TransCL have potential to aid in detecting the presence of AP and some single adverse pathologic features.

4 TECHNICAL EFFICACY: Stage 4.

No prior trial has compared hypofractionated postprostatectomy radiotherapy (HYPORT) to conventionally fractionated postprostatectomy (COPORT) in patients primarily treated with prostatectomy.

To determine if HYPORT is noninferior to COPORT for patient-reported genitourinary (GU) and gastrointestinal (GI) symptoms at 2 years.

In this phase 3 randomized clinical trial, patients with a detectable prostate-specific antigen (PSA; ≥0.1 ng/mL) postprostatectomy with pT2/3pNX/0 disease or an undetectable PSA (<0.1 ng/mL) with either pT3 disease or pT2 disease with a positive surgical margin were recruited from 93 academic, community-based, and tertiary medical sites in the US and Canada. Between June 2017 and July 2018, a total of 296 patients were randomized. Data were analyzed in December 2020, with additional analyses occurring after as needed.

Patients were randomized to receive 62.5 Gy in 25 fractions (HYPORT) or 66.6 Gy in 37 fractions (COPORT).

The coprimary end points were the 2-year change in score from baseline for the bowel and urinary domains of the Expanded Prostate Cancer Composite Index questionnaire. Secondary objectives were to compare between arms freedom from biochemical failure, time to progression, local failure, regional failure, salvage therapy, distant metastasis, prostate cancer-specific survival, overall survival, and adverse events.

Of the 296 patients randomized (median [range] age, 65 [44-81] years; 100% male), 144 received HYPORT and 152 received COPORT. At the end of RT, the mean GU change scores among those in the HYPORT and COPORT arms were neither clinically significant nor different in statistical significance and remained so at 6 and 12 months. The mean (SD) GI change scores for HYPORT and COPORT were both clinically significant and different in statistical significance at the end of RT (-15.52 [18.43] and -7.06 [12.78], respectively; P < .001). However, the clinically and statistically significant differences in HYPORT and COPORT mean GI change scores were resolved at 6 and 12 months. The 24-month differences in mean GU and GI change scores for HYPORT were noninferior to COPORT using noninferiority margins of -5 and -6, respectively, rejecting the null hypothesis of inferiority (mean [SD] GU score: HYPORT, -5.01 [15.10] and COPORT, -4.07 [14.67]; P = .005; mean [SD] GI score: HYPORT, -4.17 [10.97] and COPORT, -1.41 [8.32]; P = .02). With a median follow-up for censored patients of 2.1 years, there was no difference between HYPORT vs COPORT for biochemical failure, defined as a PSA of 0.4 ng/mL or higher and rising (2-year rate, 12% vs 8%; P = .28).

In this randomized clinical trial, HYPORT was associated with greater patient-reported GI toxic effects compared with COPORT at the completion of RT, but both groups recovered to baseline levels within 6 months. At 2 years, HYPORT was noninferior to COPORT in terms of patient-reported GU or GI toxic effects. HYPORT is a new acceptable practice standard for patients receiving postprostatectomy radiotherapy.

ClinicalTrials.gov Identifier: NCT03274687.

Prostate cancer (PCa) management is moving towards patient-tailored strategies. Advances in molecular and genetic profiling of tumor tissues, integrated with clinical risk assessments, provide deeper insights into disease aggressiveness. This study aims to offer a comprehensive overview of the pivotal genomic tests supporting PCa treatment decisions, analyzing-through real-world data-trends in their use and the growth of supporting literature evidence.

A retrospective analysis was conducted using the extensive PearlDiver™ Mariner database, which contains de-identified patient records, in compliance with the Health Insurance Portability and Accountability Act (HIPAA). The International Classification of Diseases (ICD) and Current Procedural Terminology (CPT) codes were employed to identify patients diagnosed with PCa during the study period-2011 to 2021. We determined the utilization of primary tissue-based genetic tests (Oncocyte DX®, Prolaris®, Decipher®, and ProMark®) across all patients diagnosed with PCa. Subsequently, within the overall PCa cohort, patients who underwent radical prostatectomy (RP) and received genetic testing postoperatively were identified. The yearly distribution of these tests and the corresponding trends were illustrated with graphs.

During the study period, 1,561,203 patients with a PCa diagnosis were recorded. Of these, 20,748 underwent tissue-based genetic testing following diagnosis, representing 1.3% of the total cohort. An increasing trend was observed in the use of all genetic tests. Linear regression analysis showed a statistically significant increase over time in the use of individual tests (all p-values < 0.05). Among the patients who underwent RP, 3076 received genetic analysis following surgery, representing 1.27% of this group.

Our analysis indicates a growing trend in the utilization of tissue-based genomic testing for PCa. Nevertheless, they are utilized in less than 2% of PCa patients, whether at initial diagnosis or after surgical treatment. Although it is anticipated that their use may increase as more scientific evidence becomes available, their role requires further elucidation.