5-year Biochemical Recurrence-free Survival Research Articles

Prognostic factors among patients with pathological Grade Group 5 prostate cancer based on robot-associated radical prostatectomy specimens from a large Japanese cohort (MSUG94).

There are no definitive prognostic factors for patients with pathological Grade Group 5 (pGG 5) prostate cancer (PCa) undergoing robot-associated radical prostatectomy (RARP). This study aimed to explore the prognostic factors among patients with pGG 5 PCa in a large Japanese cohort (MSUG94). This retrospective, multi-institutional cohort study was conducted between 2012 and 2021 at ten centers in Japan and included 3195 patients. Patients with clinically metastatic PCa (cN1 or cM1) and those receiving neoadjuvant and/or adjuvant therapy were excluded. Finally, 217 patients with pGG5 PCa were analyzed. The median follow-up period was 28.0months. The 3- and 5-year biochemical recurrence-free survival (BCRFS) rates of the overall population were 66.1% and 57.7%, respectively. The optimal threshold value (47.2%) for the percentage of positive cancer cores (PPCC) with any GG by systematic biopsy was chosen based on receiver operating characteristic curve analysis. Univariate analysis revealed that the prostate-specific antigen level at diagnosis, pT, pN, positive surgical margins (PSMs), lymphovascular invasion, and PPCC were independent prognostic factors for BCRFS. A multivariate analysis revealed that PSMs and PPCC were independent prognostic factors for BCRFS. Using these two predictors, we stratified BCRFS, metastasis-free survival (MFS), and castration-resistant PCa-free survival (CRPC-FS) among patients with pGG 5 PCa. The combination of PSMs and PPCC may be an important predictor of BCRFS, MFS, and CRPC-FS in patients with pGG 5 PCa undergoing RARP.

Nadir prostate-specific antigen after salvage cryotherapy as a potential prognostic factor for oncologic outcomes.

To report oncologic outcomes of patients undergoing salvage cryotherapy (SCT) for local recurrence of prostate cancer (PCa) and to establish a nadir PSA (nPSA) value that best defines long-term oncologic success. Retrospective study of men who underwent SCT for local recurrence of PCa between 2008 and 2020. SCT was performed in men with biochemical recurrence (BCR), after primary treatment and with biopsy-proven PCa local recurrence. Survival analysis with Kaplan-Meier and Cox models was performed. We determined the optimal cutoff nPSA value after SCT that best classifies patients depending on prognosis. Seventy-seven men who underwent SCT were included. Survival analysis showed a 5-year biochemical recurrence-free survival (BRFS), androgen deprivation therapy-free survival (AFS), and metastasis-free survival (MFS) after SCT of 48.4%, 62% and 81.3% respectively. On multivariable analysis for perioperative variables associated with BCR, initial ISUP, pre-SCT PSA, pre-SCT prostate volume and post-SCT nPSA emerged as variables associated with BCR. The cutoff analysis revealed an nPSA < 0.5ng/ml to be the optimal threshold that best defines success after SCT. 5-year BRFS for patients achieving an nPSA < 0.5 vs nPSA ≥ 0.5 was 64% and 9.5% respectively (p < 0.001). 5-year AFS for men with nPSA < 0.5 vs ≥ 0.5 was 81.2% and 12.2% (p < 0.001). Improved 5-year MFS for patients who achieved nPSA < 0.5 was also obtained (89.6% vs 60%, p = 0.003). SCT is a feasible rescue alternative for the local recurrence of PCa. Achieving an nPSA < 0.5ng/ml after SCT is associated with higher long-term BRFS, AFS and MFS rates.

Phase II study of pembrolizumab in combination with radiation with or without olaparib in localized high-risk prostate cancer.

TPS351 Background: Definitive radiation therapy (DRT) combined with androgen deprivation therapy (ADT) remains the standard of care in patients with high-risk prostate cancer (HRPC) who do not want surgery. However, up to 50% experience biochemical recurrence (BCR) within 5 years. A phase 3 NCIC group reported the 10-year biochemical recurrence free survival was 63% in ADT plus DRT vs. 27% in ADT alone. There is an urgent need for effective novel combination strategies. We hypothesize combined immune sensitizing effects of PARPi and radiation will result in significant activity of immunotherapy in men with HRPC. Methods: This is a multicenter phase II randomized study to assess biochemical response rates, safety and tolerability of combined therapy in pts with localized HRPC who elected for concurrent DRT. A total of 64 pts will be randomized 1:1 to receive either pembrolizumab (P) combined with olaparib or single agent P in addition to the standard of care ADT with DRT. Hypofractionated IMRT (2.4 to 4 Gy per fraction over 4-6 weeks) will be delivered and all pts will receive adjuvant P for one year and ADT for at least 18 months. All pts will undergo germline testing. Key eligible criteria include biopsy confirmed prostate adenocarcinoma who meets at least one of the four high-risk features: 1) clinical T3a, T3b or T4, 2) N1, 3) Gleason grade group 4 or 5, and 4) PSA &gt;20 ng/ml. Patients with less than 2 cm pelvic nodes and received ADT therapy within 3months prior to study enrollment are allowed. PSA &gt;150 ng/ml and patients with distant metastases will be excluded. The primary endpoint is to assess the proportion of patients who achieve a PSA nadir level of ≤ 0.06 ng/ml within six months after completion of radiation therapy in each arm. The secondary objectives include safety/tolerability, BCR and metastasis-free survival at 3 years. BCR is defined by the Phoenix definition. The study is designed to detect a 15% improvement in PSA nadir ≤ 0.06 ng/mL within 6 months after completion of the combined therapy versus historical control group data Geara FB et al., 2017. Enrollment began in August 2023. Clinical trial information: NCT05568550 .

Comprehensive analysis of alternative splicing across multiple transcriptomic cohorts reveals prognostic signatures in prostate cancer

BackgroundAlternative splicing (AS) plays a crucial role in transcriptomic diversity and is a hallmark of cancer that profoundly influences the development and progression of prostate cancer (PCa), a prevalent and potentially life-limiting cancer among men. Accumulating evidence has highlighted the association between AS dysregulation and the onset and progression of PCa. However, a comprehensive and integrative analysis of AS profiles at the event level, utilising data from multiple high-throughput cohorts and evaluating the prognosis of PCa progression, remains lacking and calls for thorough exploration.ResultsWe identified a differentially expressed retained intron event in ZWINT across three distinct cohorts, encompassing an original array-based dataset profiled by us previously and two RNA sequencing (RNA-seq) datasets. Subsequent in-depth analyses of these RNA-seq datasets revealed 141 altered events, of which 21 demonstrated a significant association with patients’ biochemical recurrence-free survival (BCRFS). We formulated an AS event-based prognostic signature, capturing six pivotal events in genes CYP4F12, NFATC4, PIGO, CYP3A5, ALS2CL, and FXYD3. This signature effectively differentiated high-risk patients diagnosed with PCa, who experienced shorter BCRFS, from their low-risk counterparts. Notably, the signature's predictive power surpassed traditional clinicopathological markers in forecasting 5-year BCRFS, demonstrating robust performance in both internal and external validation sets. Lastly, we constructed a novel nomogram that integrates patients’ Gleason scores with pathological tumour stages, demonstrating improved prognostication of BCRFS.ConclusionsPrediction of clinical progression remains elusive in PCa. This research uncovers novel splicing events associated with BCRFS, augmenting existing prognostic tools, thus potentially refining clinical decision-making.

878 Outcomes of Men Undergoing Surgery for Gleason 8-10 Prostate Cancer: A Single Centre Retrospective Study

Abstract Aim In this retrospective study, we evaluate patient outcomes for patients with localised Gleason 8-10 prostate cancer opting for radical prostatectomy. Method A list of men with Gleason 8-10 localised prostate cancer on pre-operative prostate biopsy who underwent radical prostatectomy (RP) within our tertiary referral unit between 1st January 2002 and 2nd June 2020 were obtained through departmental operative and histology records. Electronic patient record systems were retrospectively reviewed for demographic information, pre-op PSA, biopsy histology, clinical staging, type of prostatectomy, final histology, post-operative information (PSA, time to biochemical recurrence, time to metastasis, duration of urology follow-up). Results 104 patients with Gleason 8-10 disease underwent RP, with median follow-up period of 65 months. Mean (± SD) age at operation was 64.2 ± 6.1 years. Prostate biopsies revealed Gleason 9 disease in 54.8%, Gleason 8 in 40.4% and Gleason 10 in 4.8%. 28% of RP were performed laparoscopically, and 49% robot-assisted. 27% of patients had T3b status at surgery, and 7% had positive lymph nodes. 57.5% of all patients had positive surgical margins. 7.7% of patients required adjuvant radiotherapy, and 28.8% underwent salvage radiotherapy. 5-year overall survival was 90.9%; 10 year overall survival 77.1%. 5- and 10-year biochemical recurrence-free survival rates were 76.3% and 52.9% respectively; 5 and 10 year metastasis-free survival rates were 87.3% and 70.6% respectively. Conclusions Whilst many men who have radical prostatectomy for Gleason 8-10 prostate cancer develop biochemical recurrence, overall and metastasis-free survival rates are acceptable.

The impact of previous inguinal mesh hernioplasty on oncological and patient-reported outcomes following radical prostatectomy.

The impact of previous inguinal mesh hernioplasty (MH) with non-resorbable mesh prostheses on surgical performance of radical prostatectomy (RP) has been controversially discussed, with unknown impact of MH on oncologic outcomes and health-related quality of life (HRQOL) following RP. We therefore aimed to assess the influence of previous MH on metastasis-free survival (MFS), biochemical recurrence-free survival (BRFS), and HRQOL following RP. We identified 344 patients with previous MH prior RP within our prospectively assessed institutional database of 6275 patients treated with RP for PC (2008-2019). A 1:3 propensity-score matched analysis of 1345 men (n = 319 previous MH, n = 1026 no previous MH) was conducted. Primary endpoint was MFS and secondary endpoints were BRFS and HRQOL (based on EORTC QLQ-C30). Binary logistic regression, Kaplan-Meier, and Cox regression models tested the effect of previous MH on MFS, BRFS, and HRQOL (p < 0.05). Median follow-up was 47 months. Patients with previous MH had significantly lower 5-year MFS (72% vs. 85%, p < 0.001) and 5-year BRFS estimates (43% vs. 57%, p < 0.001). In multivariate analysis, previous MH was confirmed as an independent predictor for impaired MFS (hazard ratio [HR]: 3.772, 95% CI 1.12-12.64, p = 0.031) and BRFS (HR: 1.862, 95% CI: 1.22-2.85, p = 0.004). These results held true if stratified for surgical approach or limited to patients with successful PLND. We found significantly shorter median time to continence recovery for patients without previous MH (p = 0.001) without significant differences in total continence recovery rates, erectile function recovery, and HRQOL. Our findings show an impaired oncologic outcome for patients with previous MH following RP with no significant differences regarding continence recovery, erectile function recovery, and general HRQOL.

Treatment Results of High-dose-rate Brachytherapy and External Beam Radiation With Long-term Androgen Deprivation Therapy for Patients With Metastatic Prostate Cancer.

A recent clinical trial indicated the usefulness of local radiation therapy of the prostate in patients with low-volume metastatic prostate cancer. High-dose-rate brachytherapy (HDR-BT) is used mainly for high-risk, localized, and locally advanced cases. However, few studies exist on the efficacy of HDR-BT and external beam radiation therapy (EBRT) for metastatic prostate cancer. We conducted a retrospective analysis of 39 patients diagnosed with regional lymph node metastasis and/or a limited number of metastases who underwent HDR-BT and EBRT with long-term androgen deprivation therapy. We utilized Cox's proportional hazards models to identify predictors of oncological outcomes. Treatment outcomes, including biochemical recurrence-free survival (BCRFS), clinical progression-free survival (CPFS), and castration-resistant prostate cancer-free survival (CRPCFS), were compared according to the clinical stage. The median follow-up duration was 49 months (range=23-136 months). The 5-year BCRFS, CPFS, CRPCFS, and cancer-specific survival rates were 62.2%, 67.2%, 83.2%, and 93.4%, respectively. Based on Kaplan-Meier analysis, N1M0 and N0-1M1b showed favorable outcomes compared with N1M1a. Multivariate analysis revealed that N1M1a prostate cancer was an independent risk factor for poor BCRFS, CPFS, and CRPCFS. HDR-BT and EBRT with androgen deprivation therapy is a feasible approach for patients with newly diagnosed regional and low-metastatic-burden prostate cancer. However, in our cohort M1a prostate cancer had significantly inferior outcomes. A well-controlled prospective study is imperative to confirm our results.

Clinicopathologic Significance of Anterior Prostate Cancer: Comparison With Posterior Prostate Cancer in the Era of Multiparametric Magnetic Resonance Imaging.

Anterior prostate cancer (APC) has been considered an indolent tumor, most commonly arising in the transition zone (TZ). More recently, detection of APC has been facilitated through multiparametric magnetic resonance imaging and improved biopsy techniques, enabling earlier detection. The pathologic features and clinical significance of pure APC in a large contemporary series of well-characterized tumors have, to date, not been elucidated. Cases with APC defined as cancer present anterior to the urethra only were identified from 1761 consecutive radical prostatectomy specimens accessioned between January 2015 and August 2016. The clinicopathologic features of these cases were compared with those of pure posterior prostate cancer (PPC) and the features of anterior peripheral zone (APZ) cancers were compared with those of TZ cancers. In addition, the tumor series from 2015 to 2016 was compared with a cohort of 1054 patients accessioned before the utilization of multiparametric magnetic resonance imaging in the routine workup of patients with prostate cancer. In the 2015-2016 series, there were 188 (10.7%) patients with APC compared with 5.4% in the series from the pre-multiparametric magnetic resonance imaging era. No difference was observed between APC and PPC with regards to patient age or mean serum prostate-specific antigen at presentation. Mean tumor volume and positive surgical margin (PSM) rates were significantly higher in APC. In contrast, PPC was more commonly high grade with more frequent extraprostatic extension (EPE). None of the cases of APC had infiltration of the seminal vesicle or lymph node involvement, in contrast to PPC, with almost 14% of cases in each category. The 3- and 5-year biochemical recurrence-free survival was significantly higher in APC when compared with PPC, although this was not retained on multivariable analysis which included tumor location. On division of APCs according to anatomic zone of origin, 45% were APZ cancer and 37% TZ cancer. On comparison of APZ and TZ cancers, there were no significant differences in mean age and serum prostate-specific antigen at presentation as well as tumor volume, Gleason score, and PSM rate. High-grade malignancy (Gleason score >3 + 4=7) was seen in 26% of TZ cancers which compared with 44% of APZ cancers and 56% of PPC cancers. The rate of EPE was significantly higher in APZ when compared with TZ cancer ( P< 0.0005); however, the biochemical recurrence rate was not significantly different between the groups. The prevalence of APC in radical prostatectomy specimens has increased in recent times, in association with earlier detection at a stage amenable to curative surgical treatment. APC, when compared with PPC, is less commonly high grade with less frequent EPE, despite the APC group having larger tumors and a higher PSM rate at presentation. However, not all anterior cancers are indolent. Anterior cancers are more commonly seen in the APZ than the TZ and APZ cancers appear more locally aggressive than TZ cancers.

Multi-Institutional Clinical Outcomes of Biopsy Gleason Grade Group 5 Prostate Cancers Treated With Contemporary High-Dose Radiation and Long-Term Androgen Deprivation Therapy

AimsThis multicentric retrospective study reports long-term clinical outcomes of non-metastatic grade group 5 prostate cancers treated with external beam radiotherapy (EBRT) alone with long-term androgen deprivation therapy (ADT). Materials and methodsPatients treated across 19 institutions were studied. The key endpoints that were evaluated were 5-year biochemical recurrence-free survival (bRFS), metastases-free survival (MFS), overall survival, together with EBRT-related acute and late toxicities. The impact of various prognostic factors on the studied endpoints was analysed using univariate and multivariate analyses. ResultsAmong the 462 patients, 88% (405) had Gleason 9 disease and 31% (142) had primary Gleason pattern 5. A prostate-specific membrane antigen positron emission tomography-computed tomography scan was used for staging in 33% (153), 80% (371) were staged as T3/T4 and 30% (142) with pelvic nodal disease. The median ADT duration was 24 months; 66% received hypofractionated EBRT and 71.4% (330) received pelvic nodal irradiation. With a median follow-up of 56 months, the 5-year bRFS, MFS and overall survival were 73.1%, 77.4% and 90.5%, respectively. Primary Gleason pattern 5 was associated with worse bRFS, MFS and overall survival with hazard ratios of 0.51 (95% confidence interval 0.35 to 0.73, P < 0.001), 0.64 (95% confidence interval 0.43 to 0.96, P = 0.031) and 0.52 (95% confidence interval 0.28 to 0.97, P = 0.040), respectively, whereas pelvic nodal disease was associated with worse bRFS (hazard ratio 0.67, 95% confidence interval 0.46 to 0.98, P = 0.039) and MFS (hazard ratio 0.56, 95% confidence interval 0.37 to 0.85, P = 0.006). The acute and late radiation-related toxicities were low overall and pelvic nodal irradiation was associated with higher toxicities. ConclusionContemporary EBRT and long-term ADT led to excellent 5-year clinical outcomes and low rates of toxicity in this cohort of non-metastatic grade group 5 prostate cancers. Primary Gleason pattern 5 and pelvic node disease portends inferior clinical outcomes.

Direct Comparison of Two Different Definitions with Biochemical Recurrence after Low-Dose-Rate Brachytherapy for Prostate Cancer

We aimed to determine whether biochemical recurrence-free survival (BRFS) of patients with prostate cancer (PCa) who received low-dose-rate brachytherapy (LDR-BT) differed according to the definition of biochemical recurrence (BCR) after radical prostatectomy (RP) and the definition given by the Japanese Prostate Cancer Outcome Study of Permanent Iodine-125 Seed Implantation (J-POPS). We reviewed the clinical records of 476 consecutive patients with PCa who received LDR-BT at the Gifu University Hospital. The primary endpoint of this study was the difference in BRFS between the two aforementioned definitions. When the follow-up period ended, 74 (15.5%) and 20 (4.2%) patients had BCR according to the RP and J-POPS definitions, respectively. The 5-year BRFS rates were 85.0% and 96.9% for the RP and J-POPS definitions, respectively (p < 0.005). According to the RP definition, the 5-year BRFS rates were 80.6% in the group aged <63 years and 86.6% in those aged ≥63 years (p = 0.050). According to the J-POPS definition, the 5-year BRFS rates were 94.1% and 97.8% in the groups aged <63 years and ≥63 years, respectively (p = 0.005). The definition of recurrence in LDR-BT may need to be reconsidered.

Outcome of Low-Dose-Rate Brachytherapy in Patients with Prostate Cancer and the Characteristics of Patients with Recurrence

In our hospital, 553 patients with clinically localized prostate cancer underwent low-dose-rate (LDR) brachytherapy between March 2007 and December 2019. The patients were stratified based on the following prognosis according to the D'Amico risk classification criteria: low-risk and intermediate-risk groups (PSA ＜10, ≦T2a, GS : 3＋4 (≦30%)) were treated with LDR brachytherapy without supplemental extra beam radiotherapy (EBRT), while some patients in the high- and intermediate-risk groups were treated with LDR and supplemental EBRT. The 5- and 10-year overall survival rates were 94.8 and 85.5%, disease-specific survival rates were 99.8 and 97.7%, and biochemical recurrence-free survival rates were 95.7 and 90.7%. By risk stratification, the 5- and 10-year biochemical recurrence-free survival rates were 98.0 and 98.0% (low risk), 96.1 and 89.6% (intermediate risk), and 90.6 and 77.3% (high risk). The LDR outcome was generally good, but, 32 recurrence cases were observed. In the recurrent group, 9 patients did not undergo the recommended therapeutic strategy and 26 patients did not undergo preoperative magnetic resonance imaging.

Patient age as a predictive factor in biochemical recurrence following brachytherapy: Oncological outcomes at a single center.

Iodine-125 low-dose-rate brachytherapy (LDR-BT) is a treatment modality utilized in both localized and advanced prostate cancer (PCa). We aimed to evaluate the long-term oncological outcomes in patients with PCa who underwent LDR-BT, at a single institution in Japan. We retrospectively reviewed the clinical records of 340 consecutive patients with localized PCa who underwent LDR-BT between August 2004 and December 2014 at our institution. Patients with low-risk PCa who had a pretreatment prostate volume >50mL received neoadjuvant androgen deprivation therapy (ADT) for at least 3months before LDR-BT. Patients with intermediate-risk PCa were treated with a combination of LDR-BT and/or external beam radiation therapy (EBRT) and/or ADT for 9months. Patients with high-risk PCa underwent LDR-BT, EBRT, and ADT for 24months. The endpoints of this study were biochemical recurrence-free survival (BRFS) and overall survival (OS). Additionally, the association between biochemical recurrence (BCR) and clinical/pathological covariates was analyzed. At the end of the follow-up period, nine patients (2.6%) showed BCR, and six patients (1.8%) developed secondary cancers after LDR-BT. The 5-year and 10-year BRFS rates were 99.4% and 95.3%, respectively. Factoring in the patients' ages, the 5-year and 10-year BRFS rates were 99.1% and 99.1%, respectively, in patients aged >63years. The rates were 100% and 89.4% in those aged ≤63years, respectively. In the multivariate analysis, age ≤63years was identified as a significant independent predictor of BCR after LDR-BT. Age ≤63years was a significant predictor of BCR following LDR-BT. Although the risk of secondary malignant neoplasms should be considered when opting for LDR-BT in younger patients with PCa, the prevalence of them in these patients is relatively low. Therefore, clinicians should weigh the risks and benefits of definitive therapy in PCa, particularly in younger patients.

A comparison between high dose rate brachytherapy and stereotactic body radiotherapy boost after elective pelvic irradiation for high and very high-risk prostate cancer.

PurposeTo compare biochemical recurrence-free survival (BRFS) and toxicity outcomes of high dose rate brachytherapy (HDRB) and stereotactic body radiotherapy (SBRT) boost after elective nodal irradiation for high/very high-risk prostate cancer.Materials and MethodsA retrospective analysis was performed in 149 male patients. In 98 patients, the boost to the prostate was delivered by HDRB as 2 fractions of 10 Gy (EQD2 for α/β = 1.5; 66 Gy) or 1 fraction of 15 Gy (EQD2 for α/β = 1.5; 71 Gy). In 51 male patients, SBRT was used for the boost delivery (3 fractions of 7 Gy; EQD2 for α/β = 1.5; 51 Gy) because brachytherapy equipment was out of order. ResultsIn 98 patients that received HDRB boost, 3- and 5-year BRFS were 74.6% and 66.8%. Late grade-II genitourinary toxicity was detected in 27, grade-III in 1 case. Grade-II (maximum) rectal toxicity was diagnosed in nine patients. For 51 male patients that received SBRT boost, 3- and 5-year BRFS was 76.5% and 67.7%. Late grade-II (maximum) genitourinary toxicity was detected in five cases, late grade-II rectal toxicity in four cases. Other three patients developed late grade-III–IV rectal toxicity that required diverting colostomy. SBRT boost was associated with higher maximum dose to 2 cm3 of anterior rectal wall (D2cm³rectum) compared to HDRB: 92% versus 55% of dose to prostate. Severe rectal toxicity was negligible at EQD2 D2cm³rectum <85 Gy and EQD2 D5cm³ rectum <75 Gy.ConclusionOur results indicate similar 3- and 5-year BRFS in patients with high/very high-risk prostate cancer who received HDRB or SBRT boost, but SBRT boost is associated with higher rate of severe late rectal toxicity.

Long-term outcomes of whole gland high-intensity focused ultrasound for localized prostate cancer.

To report the 10-year oncologic and functional outcomes of whole-gland HIFU as first-line treatment for localized prostate cancer (PCa). Patients were retrospectively included between January 2005 and July 2018 from a prospectively maintained database at a single academic institution. No patient underwent androgen deprivation therapy prior to HIFU. Primary endpoint was biochemical recurrence-free survival (BRFS). Secondary oncological endpoints included salvage treatment-free survival (STFS), cancer-specific survival (CSS) and overall survival (OS). A total of 97 patients met our inclusion criteria and were included in the final analysis. According to D'Amico classification, the numbers of patients with low-, intermediate-, and high-risk disease were 38 (39.2%), 52 (53.6%), and 7 (7.2%). A total of 21 (21.6%) patients received salvage treatment at a mean of 4.1years (± 2.8) after HIFU. The 10-year OS, CSS and BRFS rates were 91.8%, 100% and 40.3% in the overall cohort, respectively. In multivariate analysis, predictive factors for biochemical recurrence were intermediate-risk group (RR = 2.065; 95% CI 1.008-4.230; p = 0.047) and PSA nadir > 0.5ng/mL (RR = 4.963; 95% CI 2.251-10.947; p < 0.001). Symptoms related to bladder outlet obstruction were the most frequently recorded adverse events. In multivariate analysis, positive biopsy on the prostatic apex was predictor of obstructive complications (RR = 3.2, 95% CI 1.092-9.476, p = 0.034). Only four patients developed severe urinary incontinence (> 1 pad/day). HIFU showed low PCa-specific mortality, but biochemical recurrence rates were highly variable among patients. Future studies are needed to improve patient selection.

Nomogram Predicting Adverse Pathology Outcome on Radical Prostatectomy in Low-Risk Prostate Cancer Men

ObjectiveTo develop and validate a prediction model to predict the risk of adverse pathology outcome on final pathology in low-risk prostate cancer (PCa) men. Materials and MethodsThis study was a monocentric retrospective analysis of 426 men who underwent radical prostatectomy (RP) for low-risk PCa. The validation cohort included 103 men from another hospital. Adverse pathology outcome was defined either by upgrading on RP Gleason Score (GS) (from GS 3+3 to GS ≥ 3+4 with Gleason pattern 4 ≥ 10%) or a non-organ confined disease (pathologic stage ≥ pT3a). Multivariable logistic regression analysis was performed to build nomogram for predicting adverse pathology outcome. Nomogram validation was performed by calculating the area under receiver operating characteristic curves (AUC) and comparing nomogram-predicted probabilities with actual rates of adverse pathology outcome in the external cohort. The Kaplan-Meier method was used to estimate and compare the biochemical recurrence-free survival rates between the two groups. ResultsOf 426 men in the development cohort, 45.7% showed adverse pathology outcome on RP. Age, body mass index, prostate specific antigen density, history of prior negative biopsy, magnetic resonance imaging prostate imaging reporting and data system score 4-5 and percentage of positive biopsies were significant predictors in multivariate analysis. A nomogram was constructed with an area under curve of 87%. There was agreement between predicted and actual rates of adverse pathology outcome in the validation cohort. The 5-year biochemical recurrence-free survival rates in patients with and without adverse pathology outcome was 70% and 98%, respectively. ConclusionThis novel nomogram would help identify low-risk PCa men at risk of adverse pathology outcome and can be relevant for treatment decision-making.

Pathological features of Prostate Imaging Reporting and Data System (PI-RADS) 3 MRI lesions in biopsy and radical prostatectomy specimens.

To assess the whole pathology spectrum of Prostate Imaging Reporting and Data System (PI-RADS) 3 lesions, identified on magnetic resonance imaging, using systematic (SB), targeted biopsy (TB) and radical prostatectomy (RP) specimen analysis. From a prospective database of patients undergoing RP after a combination of SB (median 12 cores) and fusion TB (median 3 cores), we included 150 PI-RADS 3 cases. Clinically significant prostate cancer (csPCa) was defined by a Grade Group 2 or more. The primary endpoints were unfavourable features in RP specimens. Targeted biopsy was negative in 20.7% of patients. Final Grade Group 3 or more and a pT3 stage was reported in 36.7% and 38.7% of RP specimens. The upgrading rate was 38.2% between biopsy and RP specimens. The concordance rate between Grade Group on TB and RP was only 38.0%. The two independent predictive factors for unfavourable disease (pT3-4 and/or final Grade Group 3-5) were prostate-specific antigen density (PSAD; P = 0.001) and presence of csPCa on TB (odds ratio 3.7; P = 0.001). The risk of unfavourable disease was increased 2.3-fold and 5.8-fold, respectively, for patients with a PSAD between 0.15 and 0.20, and a PSAD >0.20 ng/mL/g. The 5-year biochemical recurrence-free survival rate was 93.2%. PI-RADS 3 lesions exhibited aggressive features in almost 40% of cases. PSAD and presence of csPCa on TB are independent predictive factors for high-grade and/or extraprostatic disease. A combination of SB and TB improve grade prediction compared to use of TB alone.

Adjuvant Low-dose Statin Use after Radical Prostatectomy: The PRO-STAT Randomized Clinical Trial.

Statin use is reportedly associated with the risk of prostate cancer, outcomes after treatment, and prostate cancer-specific mortality. We sought to determine the efficacy of adjuvant atorvastatin in prostate cancer after radical prostatectomy. In this randomized, double-blind trial, we assigned patients with pathologic high-risk prostate cancer to receive either low-dose atorvastatin (20 mg/day, n = 183) or placebo (n = 181) for 1 year after radical prostatectomy. The primary endpoint was the 1-year biochemical recurrence rate. The secondary endpoints included the 5-year biochemical recurrence-free survival and changes in lipid, testosterone, and sex hormone binding globulin levels. From October 2012 through January 2019, a total of 364 patients underwent randomization. Among 59 total primary end points, 30 (16.4%) and 29 (16.0%) occurred in the atorvastatin and placebo groups, respectively. Atorvastatin did not significantly reduce the primary endpoint of 1-year biochemical recurrence [HR, 0.96; 95% confidence interval (CI), 0.58-1.60]. During a median follow-up of 24 months, 131 patients experienced biochemical recurrence (68 in the atorvastatin group and 63 in the placebo group), representing Kaplan-Meier estimated event rates of 24.0% and 25.4% in the atorvastatin and placebo groups, respectively, at 24 months (HR, 1.00; 95% CI, 0.71-1.41). We observed no significant between-group differences in the testosterone and sex hormone binding globulin levels. Among patients with high-risk pathologic features after radical prostatectomy for prostate cancer, 1-year adjuvant use of atorvastatin was not associated with a lower risk of disease recurrence compared with that for placebo. (ClinicalTrials.gov number, NCT01759836).See related commentary by Murtola and Siltari, p. 4947.

Magnetic resonance imaging-guided stereotactic body radiotherapy for prostate cancer (mirage): a phase iii randomized trial

BackgroundStereotactic body radiotherapy (SBRT) is becoming increasingly used in treating localized prostate cancer (PCa), with evidence showing similar toxicity and efficacy profiles when compared with longer courses of definitive radiation. Magnetic resonance imaging (MRI)-guided radiotherapy has multiple potential advantages over standard computed tomography (CT)-guided radiotherapy, including enhanced prostate visualization (abrogating the need for fiducials and MRI fusion), enhanced identification of the urethra, the ability to track the prostate in real-time, and the capacity to perform online adaptive planning. However, it is unknown whether these potential advantages translate into improved outcomes. This phase III randomized superiority trial is designed to prospectively evaluate whether toxicity is lower after MRI-guided versus CT-guided SBRT.MethodsThree hundred men with localized PCa will be randomized in a 1:1 ratio to SBRT using CT or MRI guidance. Randomization will be stratified by baseline International Prostate Symptom Score (IPSS) (≤15 or > 15) and prostate gland volume (≤50 cc or > 50 cc). Five fractions of 8 Gy will be delivered to the prostate over the course of fourteen days, with or without hormonal therapy and elective nodal radiotherapy (to a dose of 5 Gy per fraction) as per the investigator’s discretion. The primary endpoint is the incidence of physician-reported acute grade ≥ 2 genitourinary (GU) toxicity (during the first 90 days after SBRT), as assessed by the CTCAE version 4.03 scale. Secondary clinical endpoints include incidence of acute grade ≥ 2 gastrointestinal (GI) toxicity, 5-year cumulative incidences of physician-reported late grade ≥ 2 GU and GI toxicity, temporal changes in patient-reported quality of life (QOL) outcomes, 5-year biochemical recurrence-free survival and the proportion of fractions of MRI-guided SBRT in which online adaptive radiotherapy is used.DiscussionThe MIRAGE trial is the first randomized trial comparing MRI-guided with standard CT-guided SBRT for localized PCa. The primary hypothesis is that MRI-guided SBRT will lead to an improvement in the cumulative incidence of acute grade ≥ 2 GU toxicity when compared to CT-guided SBRT. The pragmatic superiority design focused on an acute toxicity endpoint will allow an early comparison of the two technologies.Trial registrationClinicaltrials.gov identifier: NCT04384770. Date of registration: May 12, 2020.https://clinicaltrials.gov/ct2/show/NCT04384770Protocol versionVersion 2.1, Aug 28, 2020.

Grading of Multifocal Prostate Cancer Cases in which the Largest Volume and the Highest Grade Do Not Coincide within One Lesion.

In general, the index lesion of prostate cancer has the largest tumor volume, the highest Grade Group (GG), and the highest stage (concordant cases). However, these factors sometimes do not coincide within one lesion (discordant cases). In such discordant cases, the largest tumor may not be of biological significance and the secondary tumor may more greatly impact the prognosis. We retrospectively reviewed the medical records of patients who underwent radical prostatectomy, and we identified 580 (85.3%) concordant cases and 100 (14.7%) discordant cases. The end point of this study was biochemical recurrence, and median followup was 4.2 years. Among discordant cases in which GGs of the largest tumor and the highest GG tumor differed, the majority (67 patients) had the largest tumor of GG 2, and we set them as the study cohort. On the other hand, we regarded 212 concordant cases with an index tumor of GG 2 as the control cohort. The study cohort comprised 48 (71.6%) patients with a secondary tumor of GG 3 and 19 (28.4%) with a secondary tumor of GG 4/5. Kaplan-Meier curves revealed that the 5-year biochemical recurrence-free survival rates were 76%, and 67%, respectively. The 5-year biochemical recurrence-free survival rate of the control cohort was 91%, which was significantly better than that of the study cohort (p=0.013 and p=0.014, respectively). Our study suggests that the prognosis of discordant cases is better determined by the secondary cancer lesion with the highest GG instead of the largest lesion.

Therapeutic Consequences of Omitting a Pelvic Lymph Node Dissection at Radical Prostatectomy when Grade and/or Stage Increase

To analyze the effect on biochemical recurrence (BCR) of omitting PLND in subsequently upgraded/upstaged patients (pNx regret). Using nomograms, patients with low to intermediate-risk prostate cancer can be selected to omit a pelvic lymph node dissection (PLND) at the time of a radical prostatectomy (RP). However, some patients will experience upgraded pathology and/or stage. We searched a prospectively maintained single institution/multi-surgeon cohort of patients treated by RP and >5-year follow-up. From 2006-2012, 1026 (521 pNx and 505 pN0/1) eligible patients with biopsy Gleason Score ≤3+4 and cT1c-cT2 undergoing RARP were included in the study. Gleason upgrading from ≤3+4 to >3+4 and/or pT3-4 occurred in 17% of pNx and 32% of pN0/N1 (p<0.001). BCR occurred in 5% of the pNx, and 7% of the PLND group. Five-year BCR free survival was higher in the pNx group (94.7% vs. 91%, P = .048). BCR occurred in 3% in the non-pNx regret and 18% in the pNx regret patients. However, with propensity score matching with pNx regret and pN0/N1 patients, 5-year BCR free survival rates were similar (81% vs 77%, P = .466). Low to favorable intermediate-risk patients who PLND was omitted and experienced upgrading or upstaging (pNx regret), have a higher predicted BCR. However, when matched to a similar cohort with pN0/N1, the BCR did not differ. Omission of a PLND does not appear to alter the rates of BCR compared to PLND inclusion.