The association between patient and disease characteristics, and the risk of disease progression in patients with prostate cancer on active surveillance.

PURPOSE: The objective of this study was to identify and assess patient and disease characteristics associated with an increased risk of disease progression in men with prostate cancer on active surveillance. METHODS: We studied patients with low-risk (ISUP GG1) or favorable intermediate-risk (ISUP GG2) PCa. All patients had at least one repeat biopsy. Disease progression was the primary outcome of this study, based on pathological upgrading. Univariate and multivariate Cox proportional hazard analyses were used to evaluate the association between covariates and disease progression. RESULTS: In total, 240 men were included, of whom 198 (82.5%) were diagnosed with low-risk PCa and 42 (17.5%) with favorable intermediate-risk PCa. Disease progression was observed in 42.9% (103/240) of men. Index lesion > 10 mm (HR = 2.85; 95% CI 1.74-4.68; p < 0.001), MRI (m)T-stage 2b/2c (HR = 2.52; 95% CI 1.16-5.50; p = 0.02), highest PI-RADS score of 5 (HR 3.05; 95% CI 1.48-6.28; p = 0.002) and a higher PSA level (HR 1.06; 95% CI 1.01-1.11; p = 0.014) at baseline were associated with disease progression on univariate analysis. Multivariate analysis showed no significant baseline predictors of disease progression. CONCLUSION: In AS patients with low-risk or favorable intermediate-risk PCa, diameter of index lesion, MRI (m)T-stage, height of the PI-RADS score and the PSA level at baseline are significant predictors of disease progression to first repeat biopsy.

Remote surgical education using synthetic models combined with an augmented reality headset.

Objective: The objective was to investigate the use of an augmented reality headset to remotely train clinicians on medical devices using anatomic models. Design: Disease-specific phantoms were developed to train physicians in mpMRI-guided fusion prostate biopsy, brachytherapy, and rectal spacer insertion. Training was remotely demonstrated using 1-way virtual video conferencing format. Participants responded to an educational content survey. A heads-up display with software and augmented reality was used for remote 2-way training with the proctor and student using on their own phantoms. Setting: The virtual video meeting took place during a prostate cancer conference in 2020, while the augmented reality training occurred in 2021. The proctor and student wore a heads-up display containing a projector and webcam where the ultrasound image was displayed onto a see-through optic along with the physician's hands. The heads-up display allowed the proctor to teach by line-of-sight while the student watched and repeated the steps. Participants: Faculty with expertise with the medical devices used in these procedures provided training to urologists unfamiliar with these techniques. Results: Participants responded that the 1-way training on the phantoms was realistic and mimicked human tissue. A total of 70.9% requested more training or training on the phantoms. The remote training platform was successfully beta tested at the 2 locations in transperineal prostate biopsy and rectal spacer insertion. Conclusion: Remote training using augmented reality eliminates the need for travel. For training programs and workshops, this technology may mitigate the risk of infectious exposures, reduce training cost, and increase proctor availability, allowing training from their own institution or clinic.This investigation qualifies for the Accreditation Council for Graduate Medical Education competency in medical knowledge.

A Prospective Multicenter Comparison Study of Risk-adapted Ultrasound-directed and Magnetic Resonance Imaging-directed Diagnostic Pathways for Suspected Prostate Cancer in Biopsy-naïve Men.

BACKGROUND: European Association of Urology guidelines recommend a risk-adjusted biopsy strategy for early detection of prostate cancer in biopsy-naïve men. It remains unclear which strategy is most effective. Therefore, we evaluated two risk assessment pathways commonly used in clinical practice. OBJECTIVE: To compare the diagnostic performance of a risk-based ultrasound (US)-directed pathway (Rotterdam Prostate Cancer Risk Calculator [RPCRC] #3; US volume assessment) and a magnetic resonance imaging (MRI)-directed pathway. DESIGN, SETTING, AND PARTICIPANTS: This was a prospective multicenter study (MR-PROPER) with 1:1 allocation among 21 centers (US arm in 11 centers, MRI arm in ten). Biopsy-naïve men with suspicion of prostate cancer (age ≥50 yr, prostate-specific antigen 3.0-50 ng/ml, ± abnormal digital rectal examination) were included. INTERVENTION: Biopsy-naïve men with elevated risk of prostate cancer, determined using RPCRC#3 in the US arm and Prostate Imaging Reporting and Data System scores of 3-5 in the MRI arm, underwent systematic biopsies (US arm) or targeted biopsies (MRI arm). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was the proportion of men with grade group (GG) ≥2 cancer. Secondary outcomes were the proportions of biopsies avoided and GG 1 cancers detected. Categorical (nonparametric) data were assessed using the Mann-Whitney U test and χ2 tests. RESULTS AND LIMITATIONS: A total of 1965 men were included in the intention-to-treat population (US arm n = 950, MRI arm n = 1015). The US and MRI pathways detected GG ≥2 cancers equally well (235/950, 25% vs 239/1015, 24%; difference 1.2%, 95% confidence interval [CI] -2.6% to 5.0%; p = 0.5). The US pathway detected more GG 1 cancers than the MRI pathway (121/950, 13% vs 84/1015, 8.3%; difference 4.5%, 95% CI 1.8-7.2%; p < 0.01). The US pathway avoided fewer biopsies than the MRI pathway (403/950, 42% vs 559/1015, 55%; difference -13%, 95% CI -17% to -8.3%; p < 0.01). Among men with elevated risk, more GG ≥2 cancers were detected in the MRI group than in the US group (52% vs 43%; difference 9.2%, 95% CI 3.0-15%; p < 0.01). CONCLUSIONS: Risk-adapted US-directed and MRI-directed pathways detected GG ≥2 cancers equally well. The risk-adapted US-directed pathway performs well for prostate cancer diagnosis if prostate MRI capacity and expertise are not available. If prostate MRI availability is sufficient, risk assessment should preferably be performed using MRI, as this avoids more biopsies and detects fewer cases of GG 1 cancer. PATIENT SUMMARY: Among men with suspected prostate cancer, relevant cancers were equally well detected by risk-based pathways using either ultrasound or magnetic resonance imaging (MRI) to guide biopsy of the prostate. If prostate MRI availability is sufficient, risk assessment should be performed with MRI to reduce unnecessary biopsies and detect fewer irrelevant cancers.

Clinical implementation of pre-biopsy magnetic resonance imaging pathways for the diagnosis of prostate cancer.

OBJECTIVE: To assess the outcomes of pre-biopsy magnetic resonance imaging (MRI) pathways, as a tool in biopsy-naïve men with suspicion of prostate cancer, in routine clinical practice. Secondary outcomes included a comparison of transrectal MRI-directed biopsy (TR-MRDB) and transperineal (TP)-MRDB in men with suspicious MRI. PATIENTS AND METHODS: We retrospectively assessed a two-centre cohort of consecutive biopsy-naïve men with suspicion of prostate cancer who underwent a Prostate Imaging-Reporting and Data System version 2 (PI-RADS v2) compliant pre-biopsy MRI in a single, high-volume centre between 2015 and 2019 (Centre 1). Men with suspicious MRI scans underwent TR-MRDB in Centre 1 and TP-MRDB with additional random biopsies (RB) in Centre 2. The MRI and histopathology were assessed in the same institution (Centre 1). Outcomes included: (i) overall detection rates of Grade Group (GG) 1, GG ≥2, and GG ≥3 cancer in men with suspicious MRI; (ii) Biopsy-avoidance due to non-suspicious MRI; and (iii) Cancer detection rates and biopsy-related complications between TR- and TP-MRDB. To reduce confounding bias for MRDB comparisons, inverse probability weighting (IPW) was performed for age, digital rectal examination, prostate-specific antigen (PSA), prostate volume, PSA density, and PI-RADS category. RESULTS: Of the 2597 men included, the overall GG 1, GG ≥2, and GG ≥3 prevalence was 8% (210/2597), 27% (697/2597), and 15% (396/2597), respectively. Biopsy was avoided in 57% (1488/2597) of men. After IPW, the GG 1, GG ≥2 and GG ≥3 detection rates after TR- and TP-MRDB were comparable at 24%, 57%, and 32%; and 18%, 64%, and 38%, respectively; with mean differences of -5.7% (95% confidence interval [CI] -13% to 1.4%), 6.1% (95% CI -2.1% to 14%), and 5.7% (95% CI -1.7% to 13%). Complications were similar in TR-MRDB (0.50%) and TP-MRDB with RB (0.62%; mean difference 0.11%, 95% CI -0.87% to 1.1%). CONCLUSION: This high-volume, two-centre study shows pre-biopsy MRI as a decision tool is implementable in daily clinical practice. Compared to recent trials, a substantially higher biopsy avoidance rate was achieved without compromising GG ≥2/GG ≥3 detection and coinciding with lower over detection rates of GG 1 cancer. Prostate cancer detection and complication rates were comparable for TR- and TP-MRDB.

Multiparametric Magnetic Resonance Imaging for the Detection of Clinically Significant Prostate Cancer: What Urologists Need to Know. Part 4: Transperineal Magnetic Resonance-Ultrasound Fusion Guided Biopsy Using Local Anesthesia.

BACKGROUND: Transperineal magnetic resonance imaging-transrectal ultrasound fusion guided biopsy (MFGB) is an increasingly popular technique due to increasing rates of biopsy-related infections. However, its widespread implementation has been hampered by the supposed necessity of epidural or general anesthesia. OBJECTIVE: To demonstrate the technique, feasibility, and results of transperineal MFGB under local anesthesia, in an ambulatory setting without the administration of prophylactic antibiotics. DESIGN, SETTING, AND PARTICIPANTS: This single-center study enrolled consecutive biopsy-naïve men with a clinical suspicion of prostate cancer into a prospective database between November 2015 and November 2020. Men with Prostate Imaging Reporting and Data System (PI-RADS) version 2 scores 3-5 underwent transperineal MFGB. SURGICAL PROCEDURE: Transperineal MFGB was performed in an ambulatory setting under local anesthesia by a single operator. MEASUREMENTS: Procedure-associated adverse events were recorded. Patient discomfort during both the local anesthesia and the biopsy procedure was determined using a visual analogic scale (0-10). Detection rates of grade group (GG) ≥2 prostate cancer and the proportion of men with GG 1 cancer were assessed. RESULTS AND LIMITATIONS: A total of 1097 eligible men underwent transperineal MFGB. The complication rate was 0.73% (8/1097); complications comprised five (0.46%) urinary tract infections including one hospitalization and three (0.27%) urinary retentions. In 735 men, the median pain scores were 2 (interquartile range [IQR] 2-3) for the local anesthesia procedure and 1 (IQR 0-2) for the biopsy. Prostate cancer was detected in 84% (926/1097) of men; 66% (723/1097) had GG ≥2 and 19% (203/1097) GG 1. CONCLUSIONS: Transperineal MFGB can safely be performed as an outpatient procedure under local anesthesia in an ambulatory setting. The detection rate of clinically significant prostate cancer is high, and biopsy is well tolerated. Although no antibiotic prophylaxis was used, the rate of infectious complications is practicably negligible. PATIENT SUMMARY: This article shows how tissue samples (biopsies) can accurately be obtained from suspicious regions seen on prostate magnetic resonance imaging via needles inserted in the perineum (skin between the scrotum and the anus) in men with suspected prostate cancer. This technique appears to be very well tolerated under local anesthesia and has a lower risk of infection without antibiotic prophylaxis than the more common biopsy route through the rectum, with antibiotics.

Cone-beam CT-based adaptive planning improves permanent prostate brachytherapy dosimetry: An analysis of 1266 patients.

PURPOSE: To evaluate adaptive planning for permanent prostate brachytherapy and to identify the prostate regions that needed adaptation. METHODS AND MATERIALS: After the implantation of stranded seeds, using real-time intraoperative planning, a transrectal ultrasound (TRUS)-scan was obtained and contoured. The positions of seeds were determined on a C-arm cone-beam computed tomography (CBCT)-scan. The CBCT-scan was registered to the TRUS-scan using fiducial gold markers. If dose coverage on the combined image-dataset was inadequate, an intraoperative adaptation was performed by placing remedial seeds. CBCT-based intraoperative dosimetry was analyzed for the prostate (D90, V100, and V150) and the urethra (D30). The effects of the adaptive dosimetry procedure for Day 30 were separately assessed. RESULTS: We analyzed 1266 patients. In 17.4% of the procedures, an adaptation was performed. Without the dose contribution of the adaptation Day 30 V100 would be < 95% for half of this group. On Day 0, the increase due to the adaptation was 11.8 ± 7.2% (1SD) for D90 and 9.0 ± 6.4% for V100. On Day 30, we observed an increase in D90 of 12.3 ± 6.0% and in V100 of 4.2 ± 4.3%. For the total group, a D90 of 119.6 ± 9.1% and V100 of 97.7 ± 2.5% was achieved. Most remedial seeds were placed anteriorly near the base of the prostate. CONCLUSION: CBCT-based adaptive planning enables identification of implants needing adaptation and improves prostate dose coverage. Adaptations were predominantly performed near the anterior base of the prostate.

Comparative analysis of prostate-specific antigen free survival outcomes for patients with low, intermediate and high risk prostate cancer treatment by radical therapy. Results from the Prostate Cancer Results Study Group.

What's known on the subject? and What does the study add? Very few comparative studies to date evaluate the results of treatment options for prostate cancer using the most sensitive measurement tools. PSA has been identified as the most sensitive tool for measuring treatment effectiveness. To date, comprehensive unbiased reviews of all the current literature are limited for prostate cancer. This is the first large scale comprehensive review of the literature comparing risk stratified patients by treatment option and with long-term follow-up. The results of the studies are weighted, respecting the impact of larger studies on overall results. The study identified a lack of uniformity in reporting results amongst institutions and centres. A large number of studies have been conducted on the primary therapy of prostate cancer but very few randomized controlled trials have been conducted. The comparison of outcomes from individual studies involving surgery (radical prostatectomy or robotic radical prostatectomy), external beam radiation (EBRT) (conformal, intensity modulated radiotherapy, protons), brachytherapy, cryotherapy or high intensity focused ultrasound remains problematic due to the non-uniformity of reporting results and the use of varied disease outcome endpoints. Technical advances in these treatments have also made long-term comparisons difficult. The Prostate Cancer Results Study Group was formed to evaluate the comparative effectiveness of prostate cancer treatments. This international group conducted a comprehensive literature review to identify all studies involving treatment of localized prostate cancer published during 2000-2010. Over 18,000 papers were identified and a further selection was made based on the following key criteria: minimum/median follow-up of 5 years; stratification into low-, intermediate- and high-risk groups; clinical and pathological staging; accepted standard definitions for prostate-specific antigen failure; minimum patient number of 100 in each risk group (50 for high-risk group). A statistical analysis (standard deviational ellipse) of the study outcomes suggested that, in terms of biochemical-free progression, brachytherapy provides superior outcome in patients with low-risk disease. For intermediate-risk disease, the combination of EBRT and brachytherapy appears equivalent to brachytherapy alone. For high-risk patients, combination therapies involving EBRT and brachytherapy plus or minus androgen deprivation therapy appear superior to more localized treatments such as seed implant alone, surgery alone or EBRT. It is anticipated that the study will assist physicians and patients in selecting treatment for men with newly diagnosed prostate cancer.

Objective automated assessment of time trends in prostate edema after (125)I implantation.

PURPOSE: To present an objective automated method to determine time trends in prostatic edema resulting from iodine-125 brachytherapy. METHODS AND MATERIALS: We followed 20 patients, implanted with stranded seeds, with seven consecutive CT scans to establish a time trend in prostate edema. Seed positions were obtained automatically from the CT series. The change in seed positions was used as surrogate for edema. Two approaches were applied to model changes in volume. (1) A cylindrical model: seeds from the compared distribution were linked to the reference distribution of Day 28. After alignment, the compared distribution was scaled in cylindrical coordinates, leading to the changes in radial and craniocaudal directions. The volume changes were calculated using these scaling factors. (2) A spherical model: distances of seeds to the center of gravity of all seeds were used as a measure to model volume changes. RESULTS: With Day 28 as reference, the observed volume changes were smaller than 18% ± 6% (1 standard deviation) for the cylindrical model and 12% ± 7% for the spherical model. One day after implantation, the implanted prostate was less than 10% larger than in the reference scan for both models. Apart from Day 0, both models showed similar volume changes. CONCLUSIONS: We present an objective automated method to determine changes in the implanted prostate volume, eliminating the influence of an observer in the assessment of the prostate size. The implanted volume change was less than 18% ± 7% for the studied group of 20 patients. Edema was 9% ± 5% from 1 day after implantation onward.

An increased utilisation rate and better compliance to guidelines for primary radiotherapy for breast cancer from 1997 till 2008: a population-based study in the Netherlands.

Only scarce data are available on the utilisation rate of primary radiotherapy (RT) for patients with breast cancer. In this study, we compared the use of primary RT for patients with stages I-III breast cancer in 4 of the 9 Dutch Comprehensive Cancer Centres, focussing specifically on time trends as well as age effects. From the population-based cancer registries, we selected all females diagnosed with breast cancer between 1997 and 2008 (N=65,966, about 50% of all Dutch breast cancer patients in this period). We observed an overall increase in the use of primary RT for breast cancer patients ranging from 55-61% in 1997 to 58-68% in 2008. This can be explained by a higher rate of breast-conserving surgery (BCS), which was followed by RT in 87-99% of cases, and a reduced rate of total mastectomy (TM) which was followed by RT in 26-47% of cases. Increasing age was associated with a reduced use of RT, especially for those above 75. Finally, we observed a decrease in time of observed regional variances in the use of RT after BCS as well as after TM (for stage III disease). These findings can be attributed to the development and implementation of the Dutch nationwide guidelines for treatment of breast cancer.

Intraoperative adaptive brachytherapy of iodine-125 prostate implants guided by C-arm cone-beam computed tomography-based dosimetry.

PURPOSE: (1) To demonstrate the feasibility of C-arm cone-beam computed tomography (CBCT)-based postplanning and subsequent adaptation of underdosed critical areas by adding remedial seeds during the transrectal ultrasound (TRUS)-guided implantation of (125)I seeds and (2) to assess the duration of this procedure. METHODS AND MATERIALS: After finishing the implant, three fiducial markers were implanted and a TRUS study was performed to delineate the prostate. A C-arm CBCT unit with isocentric design was used to generate a CT data set to localize the seeds. The TRUS and CBCT data sets were coregistered by the radiation oncologist to assess the dosimetry of the implant. If underdosages existed at critical areas, dosimetry was adapted by adding remedial seeds while the patient was still under anesthesia. RESULTS: Of 20 patients studied, 9 demonstrated underdosage in critical areas. On average four additional seeds were implanted, resulting in a mean D(90) of 100.7% (increase 4.9%) and 117.5% (increase 17.8%) of the prescribed dose of 145 and 110 Gy, respectively. The average additional time involved in performing the adaptation procedure was less than 30 min. CONCLUSIONS: C-arm CBCT-guided intraoperative postplanning during TRUS-guided brachytherapy for prostate cancer is both feasible and time efficient. The adaptation resulted in improved dosimetry of the prostate implants.