Intermediate-risk Prostate Cancer Research Articles

Transperineal laser ablation of the prostate as a treatment for benign prostatic hyperplasia and prostate cancer: The results of a Delphi consensus project

ObjectiveTo evaluate transperineal laser ablation (TPLA) with Echolaser® (Echolaser® TPLA, Elesta S. p.a, Calenzano, Italy) as a treatment for benign prostatic hyperplasia (BPH) and prostate cancer (PCa) using the Delphi consensus method. MethodsItalian and international experts on BPH and PCa participated in a collaborative consensus project. During two rounds, they expressed their opinions on Echolaser® TPLA for the treatment of BPH and PCa answering online questionnaires on indications, methodology, and potential complications of this technology. Level of agreement or disagreement to reach consensus was set at 75%. If the consensus was not achieved, questions were modified after each round. A final round was performed during an online meeting, in which results were discussed and finalized. ResultsThirty-two out of forty invited experts participated and consensus was reached on all topics. Agreement was achieved on recommending Echolaser® TPLA as a treatment of BPH in patients with ample range of prostate volume, from <40 mL (80%) to >80 mL (80%), comorbidities (100%), antiplatelet or anticoagulant treatment (96%), indwelling catheter (77%), and strong will of preserving ejaculatory function (100%). Majority of respondents agreed that Echolaser® TPLA is a potential option for the treatment of localized PCa (78%) and recommended it for low-risk PCa (90%). During the final round, experts concluded that it can be used for intermediate-risk PCa and it should be proposed as an effective alternative to radical prostatectomy for patients with strong will of avoiding urinary incontinence and sexual dysfunction. Almost all participants agreed that the transperineal approach of this organ-sparing technique is safer than transrectal and transurethral approaches typical of other techniques (97% of agreement among experts). Pre-procedural assessment, technical aspects, post-procedural catheterization, pharmacological therapy, and expected outcomes were discussed, leading to statements and recommendations. ConclusionEcholaser® TPLA is a safe and effective procedure that treats BPH and localized PCa with satisfactory functional and sexual outcomes.

Long-term outcomes of ultra-hypofractionated 2 fractions single day HDR brachytherapy in localized prostate cancer

Introduction and objectivesWe previously published the toxicity and initial results of a prospective cohort of patients treated with 2 fractions HDR-BRT administered in a single day. In the present analysis we report the long-term cancer control results of our prospective trial and investigate the relationship between PSA nadir and biochemical control. Material and methodsA total of 120 patients were treated with HDR Brachytherapy monotherapy administered in two fractions in a single day. Between November 2010 and February 2016, 84 patients with low-risk and 36 patients with intermediate-risk prostate cancer in accordance with the NCCN practice guidelines. ResultsMedian age was 66 years (range 45–84) and median PSA was 7.5 ng/ml (range 0.01–16 ng/ml). Overall, 84.2% had Gleason score 6 and 15.8% Gleason 7. Thirty-one percent of patients received ADT.After a median follow-up of the cohort was 123 months. Actuarial rates of no biochemical evidence of disease (bNED), overall survival, local control and metastasis-free survival for all patients were 93.3%, 86.7%, 95.2% and 96.1%, respectively.The median time to achieve PSA nadir was 80.5 months. Patients who attained a PSA Nadir ≤ 0.20 ng/mL exhibited a 10-year bNED survival rate of 96.9%, whereas thosewho failed to reach this PSA level had a survival rate of only 40%. ConclusionsIn patients with favorable localized prostate cancer, 2 fractions HDR-BT monotherapy is a highly curative radiation technique that attains PSA nadir levels < 0.2 ng/mL in 95% of cases.

To Boost or Not to Boost: Pooled Analyses From 2-Fraction SABR Trials for Localized Prostate Cancer

Focal boost to dominant intraprostatic lesion (DIL) is an approach for dose escalation in prostate radiation therapy. In this study, we aimed to report the outcomes of 2-fraction SABR ± DIL boost. We included 60 patients with low- to intermediate-risk prostate cancer enrolled in 2 phase 2 trials (30 patients in each trial). In the 2STAR trial (NCT02031328), 26 Gy (equivalent dose in 2-Gy fractions=105.4 Gy) was delivered to the prostate. In the 2SMART trial (NCT03588819), 26 Gy was delivered to the prostate, with up to 32 Gy boost to magnetic resonance imaging-defined DIL (equivalent dose in 2-Gy fractions=156.4 Gy). The reported outcomes included prostate-specific antigen (PSA) response (ie, <0.4 ng/mL) at 4 years (4yrPSARR), biochemical failure (BF), acute and late toxicities, and quality of life (QOL). In 2SMART, median DIL D99% of 32.3 Gy was delivered. Median follow-up was 72.7 months (range, 69.1-75.) in 2STAR and 43.6 months (range, 38.7-49.5) in 2SMART. The 4yrPSARR was 57% (17/30) in 2STAR and 63% (15/24) in 2SMART (P=0.7). The 4-year cumulative BF was 0% in 2STAR and 8.3% in 2SMART (P=0.1). The 6-year BF in 2STAR was 3.5%. For genitourinary toxicities, there were differences in grade ≥1 urinary urgency in the acute (0% vs 47%; P < .001) and late settings (10% vs 67%; P < .001) favoring 2STAR. For urinary QOL, no difference was observed in the acute setting, but lower proportion in 2STAR had minimal clinically important changes in urinary QOL score in the late setting (21% vs 50%; P=.03). There were no significant differences in gastrointestinal and sexual toxicities and QOL in both acute and late settings between the 2 trials. This study presents the first prospective data comparing 2-fraction prostate SABR ± DIL boost. The addition of DIL boost resulted in similar medium-term efficacy (in 4yrPSARR and BF), with impact on late urinary QOL outcomes.

A Multicenter Phase 2 Study of Ultrahypofractionated Stereotactic Boost After External Beam Radiotherapy in Intermediate-risk Prostate Carcinoma: A Very Long-term Analysis of the CKNO-PRO Trial

BackgroundGenitourinary (GU) or gastrointestinal (GI) complications and tumor relapse can occur in the long term after radiotherapy for prostate cancer. ObjectiveTo assess the late tolerance and relapse-free survival (RFS) in patients undergoing hypofractionated stereotactic boost therapy after external beam radiotherapy (EBRT) for intermediate-risk prostate cancer. Design, setting, and participantsSeventy-six patients with intermediate-risk prostate carcinoma between August 2010 and April 2013 were included. The first course delivered a dose of 46 Gy by conventional fractionation; the second course was a boost of 18 Gy (3 × 6 Gy) within 10 d. Outcome measurements and statistical analysisGU and GI toxicities were evaluated as the primary outcomes. The secondary outcomes were overall survival and RFS. The cumulative incidence of toxicity was calculated using a competing-risk approach. Overall survival and RFS were estimated using the Kaplan-Meier method. Results and limitationsThe median follow-up period was 88 mo (range, 81–99 mo). Sixty (79%) patients were treated with the CyberKnife and 16 (21%) using a linear accelerator. The cumulative incidences of GU and GI grade ≥2 toxicities at 120 mo were 1.4% (95% confidence interval [CI]: 0.1–6.6%) and 11.0% (95% CI: 5.1–19.4%), respectively. The overall survival and RFS rates at 8 yr were 89.1% (95% CI: 77–95%) and 76.9% (95% CI: 63.1–86.1), respectively. ConclusionsA very long follow-up showed low GU and GI toxicities after a hypofractionated stereotactic boost after EBRT for intermediate-risk prostate cancer. Dose escalation of the boost delivered by hypofractionated radiation therapy appears safe for use in future trials. Patient summaryWe found low toxicity and good survival rates after a short and high-precision boost after external beam radiotherapy for intermediate-risk prostate cancer, with a long-term follow-up of 88 mo. This long-term treatment is safe and should be considered in future trials.

Long-Term Outcomes of a Prospective Study on Highly Hypofractionated Intensity Modulated Radiation Therapy for Localized Prostate Cancer for 3 Weeks

Reports of radiation therapy for prostate cancer using dose fractions between moderate hypofractionation and ultrahypofractionation are limited. This pilot study involved the application of highly hypofractionated intensity modulated radiation therapy (IMRT) in 15 fractions for 3 weeks and the number of fractions was intermediate between the 2 previously mentioned dose fractions. The long-term outcomes are reported. From April 2014 to September 2015, patients with low- to intermediate-risk prostate cancer received 54 Gy in 15 fractions (3.6 Gy per fraction) for 3 weeks using IMRT without intraprostatic fiducial markers or a rectal hydrogel spacer. Neoadjuvant hormone therapy (HT) was administered for 4 to 8 months. Adjuvant HT was not administered to any patients. Rates of biochemical relapse-free survival, clinical relapse-free survival, overall survival, and the cumulative incidence of late grade ≥2 toxicities were analyzed. Twenty-five patients were enrolled in this prospective study; 24 of them were treated with highly hypofractionated IMRT (17% had low-risk and 83% had intermediate-risk disease). The median neoadjuvant HT duration was 5.3 months. The median follow-up period was 77 months (range, 57-87 months). Biochemical relapse-free survival, clinical relapse-free survival, and overall survival rates were 91.7%, 95.8%, and 95.8% at 5 years, and 87.5%, 86.3%, and 95.8% at 7 years, respectively. Neither grade ≥2 late gastrointestinal toxicity nor grade ≥3 late genitourinary toxicity was observed. The cumulative incidence rates of grade 2 genitourinary toxicity were 8.5% and 18.3% at 5 and 7 years, respectively. Highly hypofractionated IMRT delivering 54 Gy in 15 fractions for 3 weeks for prostate cancer without intraprostatic fiducial markers facilitated favorable oncological outcomes without severe complications. This treatment approach may be a possible alternative to moderate hypofractionation, but further validation is needed.

Use of expectant management based on prostate cancer risk and health status: How far are we from a risk-adapted approach?

While active surveillance, a form of expectant management (EM), is preferred for patients with low-risk prostate cancer (PCa), some favor a more risk-adapted approach that recognizes patient preferences and condition-specific factors. However, previous research has shown non-patient-related factors often drive PCa treatment. In this context, we characterized trends in AS with respect to disease risk and health status. Using SEER-Medicare data, we identified men 66 years and older diagnosed with localized low- and intermediate-risk PCa from 2008 to 2017 and examined receipt of EM, defined as the absence of treatment (i.e., surgery, cryotherapy, radiation, chemotherapy, and androgen deprivation therapies) within 1 year of diagnosis. We performed bivariable analysis to compare trends in use for EM vs. treatment, stratified by disease risk (i.e., Gleason 3+3, 3+4, 4+3; PSA<10, 10-20) and health status (i.e., NCI Comorbidity Index (NCI), frailty, life expectancy). We then ran a multivariable logistic regression model to examine determinants of EM. Within this cohort, 26,364 (38%) were categorized as low-risk (i.e., Gleason 3+3 and PSA<10) and 43,520 (62%) as intermediate-risk (i.e., all others). Over the study period, use of EM significantly increased across all risk groups, except for Gleason 4+3 (P = 0.662), as well across all health status groups. However, linear trends did not differ significantly between frail vs. nonfrail patients for both those categorized as low-risk (P = 0.446) and intermediate-risk (P = 0.208). Trends also did not differ between NCI 0 vs. 1 vs. >1 for low-risk PCa (P = 0.395). In the multivariable models, EM was associated with increasing age and being frail for men with both low- and intermediate risk disease. Conversely, EM selection was negatively associated with higher comorbidity score. EM increased significantly over time for patients with low- and favorable intermediate-risk disease, with the most notable differences based on age and Gleason score. In contrast, trends in uptake of EM did not differ substantively by health status, suggesting that physicians may not be effectively incorporating patient health into PCa treatment decisions. Additional work is needed to develop interventions that recognize health status as an essential component of a risk-adapted approach.

Risks of alcohol and drug use disorders in prostate cancer survivors: a national cohort study.

Prostate cancer (PC) survivors may potentially use substances to cope with psychological distress or poorly controlled physical symptoms. Little is known, however, about the long-term risks of alcohol use disorder (AUD) or drug use disorders in men with PC. A national cohort study was conducted in Sweden of 180 189 men diagnosed with PC between 1998 and 2017 and 1 801 890 age-matched population-based control men. AUD and drug use disorders were ascertained from nationwide records through 2018. Cox regression was used to compute hazard ratios (HRs) while adjusting for sociodemographic factors and prior psychiatric disorders. Subanalyses examined differences by PC treatment from 2005 to 2017. Men with high-risk PC had increased risks of both AUD (adjusted HR = 1.44, 95% confidence interval [CI] = 1.33 to 1.57) and drug use disorders (adjusted HR = 1.93, 95% CI = 1.67 to 2.24). Their AUD risk was highest in the first year and was no longer significantly elevated 5 years after PC diagnosis, whereas their drug use disorders risk remained elevated 10 years after PC diagnosis (adjusted HR = 2.26, 95% CI = 1.45 to 3.52), particularly opioid use disorder (adjusted HR = 3.07, 95% CI = 1.61 to 5.84). Those treated only with androgen-deprivation therapy had the highest risks of AUD (adjusted HR = 1.91, 95% CI = 1.62 to 2.25) and drug use disorders (adjusted HR = 2.23, 95% CI = 1.70 to 2.92). Low- or intermediate-risk PC was associated with modestly increased risks of AUD (adjusted HR = 1.38, 95% CI = 1.30 to 1.46) and drug use disorders (adjusted HR = 1.19, 95% CI = 1.06 to 1.34). In this large cohort, men with PC had significantly increased risks of both AUD and drug use disorders, especially those with high-risk PC and treated only with androgen-deprivation therapy. PC survivors need long-term psychosocial support and timely detection and treatment of AUD and drug use disorders.

The Diagnostic Value of PSMA PET/CT in Men with Newly Diagnosed Unfavorable Intermediate-Risk Prostate Cancer.

Our objective was to determine the diagnostic value of prostate-specific membrane antigen (PSMA) PET/CT in staging men with newly diagnosed unfavorable intermediate-risk prostate cancer (PCa). Methods: Patients with newly diagnosed unfavorable intermediate-risk PCa, in whom PSMA PET/CT was performed as a primary staging modality, were retrospectively studied. PSMA PET/CT was performed at several diagnostic centers and reported by expert nuclear medicine physicians within 2 high-volume PCa centers. A multivariate logistic regression analysis, taking into account clinical, biochemical, pathologic, and radiologic variables, was performed to identify potential independent predictors for metastatic disease on PSMA PET/CT. Results: In total, 396 men with newly diagnosed unfavorable intermediate-risk PCa were studied. Metastatic disease was observed in 37 (9.3%) men, of whom 29 (7.3%) had molecular imaging locoregional lymph node metastases (miN1) and 16 (4.0%) had distant metastases (miM1). A radiologic tumor stage of at least T3 on MRI (odds ratio, 2.72 [95% CI, 1.27-5.83]; P = 0.01) and more than 50% positive prostate biopsies (odds ratio, 3.87 [95% CI, 1.74-8.62]; P = 0.001) were found to be independently associated with metastatic disease on PSMA PET/CT. Conclusion: Given that metastatic disease was observed in nearly 1 in 10 men with newly diagnosed unfavorable intermediate-risk PCa, PSMA PET/CT is considered to be of diagnostic value within this population. Further stratification using the radiologic tumor stage and the percentage of positive prostate biopsies could aid in identifying those patients at risk of having metastatic disease on PSMA PET/CT.

Neoadjuvant versus Concurrent Androgen Deprivation Therapy in Localized Prostate Cancer Treated with Radiotherapy: A Systematic Review of the Literature.

There is an ongoing debate on the optimal sequencing of androgen deprivation therapy (ADT) and radiotherapy (RT) in patients with localized prostate cancer (PCa). Recent data favors concurrent ADT and RT over the neoadjuvant approach. We conducted a systematic review in PubMed, EMBASE, and Cochrane Databases assessing the combination and optimal sequencing of ADT and RT for Intermediate-Risk (IR) and High-Risk (HR) PCa. Twenty randomized control trials, one abstract, one individual patient data meta-analysis, and two retrospective studies were selected. HR PCa patients had improved survival outcomes with RT and ADT, particularly when a long-course Neoadjuvant-Concurrent-Adjuvant ADT was used. This benefit was seen in IR PCa when adding short-course ADT, although less consistently. The best available evidence indicates that concurrent over neoadjuvant sequencing is associated with better metastases-free survival at 15 years. Although most patients had IR PCa, HR participants may have been undertreated with short-course ADT and the absence of pelvic RT. Conversely, retrospective data suggests a survival benefit when using the neoadjuvant approach in HR PCa patients. The available literature supports concurrent ADT and RT initiation for IR PCa. Neoadjuvant-concurrent-adjuvant sequencing should remain the standard approach for HR PCa and is an option for IR PCa.

Survival After Cryotherapy Versus Radiotherapy in Low and Intermediate Risk Localized Prostate Cancer

BackgroundFocal therapy, including cryotherapy, reduces overtreatment in low- and intermediate-risk prostate cancer (PCa) patients with multiple comorbidities, which seems to increase in popularity compared with whole gland treatment. However, there is currently no consensus regarding the medium-term outcomes of cryosurgery as a prospective alternative to radiotherapy (RT) for such patients. Our study aims to find the available evidence that directly compares the medium-term overall survival (OS) and cancer-specific mortality (CSM) outcomes between cryotherapy and RT in patients with low- and intermediated-risk PCa. Materials and MethodUsing the Surveillance, Epidemiology, and End Results (SEER) database, we identified 47,787 patients with low- and intermediate-risk PCa diagnosed between 2004 and 2015, of which 46,853 (98%) received treatment with RT, while only 934 (2.0%) received treatment with cryotherapy. Kaplan–Meier methods were used to estimateOS and cancer-specific survival (CSS) between the 2 groups. We performed multivariable Cox regression analysis to assess overall mortality (OM), while the cumulative incidence function (CIF) was used to illustrate cancer-specific mortality (CSM) and noncancer-specific mortality (non-CSM) for all patients. Additionally, competing risks regression (Fine-Gray) was implemented to evaluate any differences. After propensity score matching (PSM), all the aforementioned analyses were repeated. After the inverse probability of treatment weighting (IPTW), we repeated Kaplan–Meier methods on OS and CSS, and performed multivariable Cox regression analysis to assess OM in cryotherapy versus RT. Sensitivity analyses were conducted by excluding patients who died of cardiovascular disease. ResultsAfter applying 1:4 PSM to the cryotherapy group with the RT group, the resulting RT cohort consisted of 3,736 patients who were matched with 934 patients in the cryotherapy cohort. The 5‐year OS and cumulative CSM rates for PS-matched groups (N = 4670) receiving cryotherapy (N = 934) or RT (N = 3736) were 89% versus 91.8%, 0.65% versus 0.57, respectively. Multivariable Cox regression analysis demonstrated that cryotherapy was associated with a poorer OS outcome compared to RT (hazard ratio [HR] 1.29, 95% confidence interval [CI]: 1.07-1.55, p < .01). Multivariate competing risk regression analysis revealed that both treatments were not associated with CSS, with HR = 1.07 (95% CI: 0.55-2.08, p = .85). IPTW-adjusted analyses showed that the 5-years OS rates were 89.6% versus 91.8% for cryotherapy versus RT, respectively. Multivariate regression analysis for OS demonstrated that cryotherapy was more likely to have inferior OS in comparison to RT (HR = 1.30; 95%CI: 1.09-1.54; p < .01). The outcome of sensitivity analyses indicates that there was no significant difference in OS and CSS between the 2 groups. ConclusionFor low- and intermediate-risk PCa patients treated by cryotherapy or RT, we could not demonstrate a survival difference. Cryotherapy may be a feasible option as a viable alternative to traditional radiation therapy.

Functional outcome after radical prostatectomy in 1313 patients: A single-center study.

To assess the impact of urinary continence and erectile function on the quality of life in men undergoing radical prostatectomy (RP) for prostate cancer (PC), we analyzed the preoperative and 1-year postoperative outcomes of five functional domains and their influencing factors. In this prospective study, all patients undergoing open or robot-assisted RP between Febuary 2017 and March 2020 in a single academic center were included. Patient-reported outcomes were assessed pre- and 12 months postoperatively using the Expanded Prostate Index Composite (EPIC-26) survey, evaluating continence, irritative/obstructive micturition, gastrointestinal symptoms, sexuality, and overall vitality. We examined the impact of RP on sexual function and urinary continence using multivariable logistic regression models, accounting for patient and tumor characteristics. Overall, 1313 consecutive patients gave consent for study participation and completed both surveys. The median age was 66 years (IQR: 60-70). The majority of patients (n = 601, 46%) had an intermediate risk PC. Robotic RP was performed in 71.6% and nerve-sparing technique in 81% of the cases. The median pre- versus postoperative scores were the following: urinary continence 100 (IQR:91.8-100) versus 85.5 (64.8-100), irritative micturition 87.5 (IQR: 75-100) versus 93.8 (IQR: 87.5-100), gastrointestinal symptoms the same with 100 (IQR: 95.8-100), vitality 95 (IQR: 80-100) versus 90 (IQR: 75-100), and erectile function 65.3 (IQR: 38.8-87.5) versus 22.2 (IQR: 12.5-48.7), respectively. Age (p < 0.001), risk classification (p = 0.002), and nerve-sparing surgery (p = 0.016) were associated with good sexual function (EPIC-26 score ≥60), while only age (p = 0.001) was statistically significantly associated with good urinary continence (EPIC-26 score ≥80). Non-modifiable factors such as age and PC risk classification impact urinary continence and sexual function after RP. Nevertheless, urologic surgeons should further focus on improving nerve-sparing techniques, the only modifiable variable, to reduce the surgery's negative impact on urinary continence and sexual function.

Effect of Adequate Local Radiation Dose on Oncological Outcomes in Localized Prostate Cancer Patients Treated With Low-dose-rate Brachytherapy.

We retrospectively investigated the effect of a biologically effective dose (BED) of Low-dose rate brachytherapy (LDR-BT) and its possible interaction with androgen deprivation therapy (ADT) during LDR-BT treatment for intermediate-risk prostate cancer (PCa). A total of 693 patients with localized, intermediate-risk PCa, who underwent LDR-BT with or without supplemental external beam radiotherapy, were included in this study. We stratified patients into two groups according to BED (<180 Gy2, lower BED group; ≥180 Gy2, higher BED group) and evaluated the effect of ADT duration on the oncological outcomes of each group. In total, 431 patients received BED ≥180 Gy2. Significant differences in biochemical recurrence-free survival (BCRFS) and clinical progression-free survival (CPFS) were observed among the non-ADT, ADT ≤3 months, and ADT >3 months subgroups of the lower BED group (p=0.005 and 0.049, respectively). However, no significant differences in BCRFS or CPFS were detected in the higher BED group (p=0.63 and 0.76, respectively). Multivariate analysis of BCR and CP in the lower BED group revealed a significant decreasing trend in the BCRFS (p for trend=0.001) and CPFS rates (p for trend=0.015) as ADT duration increased, which was associated with favorable outcomes. However, no significant trend was observed in the BCRFS or CPFS rate in the higher BED group. An adequate local radiation dose provides favorable oncological outcomes and could potentially reduce the need for long-term ADT.

Editorial Comment.

No AccessJournal of UrologyAdult Urology21 Jun 2023Editorial CommentThis article comments on the following:Biopsy Assessment of Oncologic Control 3 Years Following Primary Partial Gland Cryoablation: A Prospective Cohort Study of Men With Intermediate-risk Prostate Cancer Taimur T. Shah Taimur T. ShahTaimur T. Shah Imperial Prostate, Department of Surgery and Cancer, Imperial College London, London, United Kingdom Imperial Urology, Charing Cross Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003569.01AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack Citations ShareFacebookLinked InTwitterEmail "Editorial Comment." The Journal of Urology, Publish Ahead of Print, pp. REFERENCES 1. . Biopsy assessment of oncologic control three years following primary partial gland cryoablation: a prospective cohort study of men with intermediate risk prostate cancer. J Urol. 2023; 210(3):000-000. Google Scholar 2. Fifteen-year outcomes after monitoring, surgery, or radiotherapy for prostate cancer. N Engl J Med. 2023; 388(17):1547-1558. Crossref, Medline, Google Scholar 3. PACE-A: an international phase 3 randomised controlled trial (RCT) comparing stereotactic body radiotherapy (SBRT) to surgery for localised prostate cancer (LPCa)—primary endpoint analysis. J Clin Oncol. 2023; 41(6_suppl):298. Crossref, Google Scholar 4. . MP80-16 Black patients have worse continence outcomes at 12 months following robotic-assisted radical prostatectomy. J Urol. 2023; 209(suppl 4):e1159. Abstract, Google Scholar 5. Early-medium-term outcomes of primary focal cryotherapy to treat nonmetastatic clinically significant prostate cancer from a prospective multicentre registry. Eur Urol. 2019; 76(1):98-105. Crossref, Medline, Google Scholar 6. Focal therapy compared to radical prostatectomy for non-metastatic prostate cancer: a propensity score-matched study. Prostate Cancer Prostatic Dis. 2021; 24(2):567-574. Crossref, Medline, Google Scholar © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsRelated articlesJournal of Urology7 Jun 2023Biopsy Assessment of Oncologic Control 3 Years Following Primary Partial Gland Cryoablation: A Prospective Cohort Study of Men With Intermediate-risk Prostate Cancer Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Taimur T. Shah Imperial Prostate, Department of Surgery and Cancer, Imperial College London, London, United Kingdom Imperial Urology, Charing Cross Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom More articles by this author Expand All Advertisement PDF downloadLoading ...

Current evidence for moderate and ultra-hypofractionated radiation therapy in prostate cancer: a summary of the results from phase 3 randomised trials.

A low α/β ratio for prostate cancer (PCa) compared to surrounding normal tissue theoretically implies therapeutical advantages with hypofractionated treatment. Data from large randomised control trials (RCTs) comparing moderate hypofractionated (MHRT, 2.4-3.4 Gray/fraction (Gy/fx)) and ultra-hypofractionated (UHRT, >5 Gy/fx) with conventionally fractionated radiation therapy (CFRT, 1.8-2 Gy/fx) and the possible clinical implications have been reviewed. We searched PubMed, Cochrane and Scopus for RCT comparing MHRT/UHRT with CFRT treatment of locally and/or locally advanced (N0M0) PCa. We found six RCTs, which compared different radiation therapy regimes. Tumour control and acute and late toxicities are reported. MHRT was non-inferior to CFRT for intermediate-risk PCa, non-inferior for low-risk PCa and not superior in terms of tumour control for high-risk PCa. Acute toxicity rates were increased compared to CFRT, especially an increase in acute gastrointestinal adverse effects was seen. Late toxicity related to MHRT seems to be comparable. UHRT was non-inferior in terms of tumour control in one RCT, with increased acute toxicity, but with comparable late toxicity. One trial, however, indicated increased late toxicity rates with UHRT. MHRT delivers similar therapeutic outcomes compared to CFRT in terms of tumour control and late toxicity for intermediate-risk PCa patients. Slightly more acute transient toxicity could be tolerated in favour of a shorter treatment course. UHRT should be regarded as an optional treatment for patients with low- and intermediate-risk disease applied at experienced centres in concordance with international and national guidelines.

High-dose-rate brachytherapy as monotherapy versus as boost in unfavorable intermediate-risk localized prostate cancer: A matched-pair analysis

PURPOSEHigh-dose-rate brachytherapy as monotherapy (HDR-M), or as a boost combined with external beam radiotherapy (HDR-B), are both suitable treatments for intermediate-risk prostate cancer. However, data directly comparing these two approaches for men with unfavorable intermediate-risk (UIR) patients are lacking. METHODS AND MATERIALSPatients with NCCN-defined UIR prostate cancer treated from 1997 to 2020 were identified in a prospectively maintained, single institution database. HDR-M and HDR-B patients were matched using three factors: age ±3 years; Gleason score (major and minor); and clinical T stage. Biochemical failure was defined as PSA nadir (nPSA) + 2. Available acute and chronic toxicities are additionally reported. RESULTSA total of 247 patients were identified (170 receiving HDR-B, 77 receiving HDR-M), ultimately yielding 70 matched pairs (140 patients) for inclusion. The median followup time was 5.2 years for HDR-M compared with 9.3 years for HDR-B (p < 0.001). The two cohorts had similar calculated prostate EQD2 (HDR-B 118 Gy vs. HDR-M 115 Gy, p = 0.977). No significant differences in OS, CSS, DM, LRR, or FFBF were identified. HDR-B had an increased rate of any acute grade 2+ gastrointestinal toxicity and worse acute dysuria and diarrhea. Chronic gastrointestinal and genitourinary toxicity was similar. CONCLUSIONSThese data suggest that HDR brachytherapy as monotherapy is an effective treatment option for selected patients with unfavorable intermediate-risk prostate cancer and provides a more favorable gastrointestinal toxicity profile than HDR-B. Prospective trials should be conducted to refine the selection process for this heterogeneous cohort of patients.

Effect of Brachytherapy With External Beam Radiation Therapy Versus Brachytherapy Alone for Intermediate-Risk Prostate Cancer: NRG Oncology RTOG 0232 Randomized Clinical Trial.

To determine whether addition of external beam radiation therapy (EBRT) to brachytherapy (BT) (COMBO) compared with BT alone would improve 5-year freedom from progression (FFP) in intermediate-risk prostate cancer. Men with prostate cancer stage cT1c-T2bN0M0, Gleason Score (GS) 2-6 and prostate-specific antigen (PSA) 10-20 or GS 7, and PSA < 10 were eligible. The COMBO arm was EBRT (45 Gy in 25 fractions) to prostate and seminal vesicles followed by BT prostate boost (110 Gy if 125-Iodine, 100 Gy if 103-Pd). BT arm was delivered to prostate only (145 Gy if 125-Iodine, 125 Gy if 103-Pd). The primary end point was FFP: PSA failure (American Society for Therapeutic Radiology and Oncology [ASTRO] or Phoenix definitions), local failure, distant failure, or death. Five hundred eighty-eight men were randomly assigned; 579 were eligible: 287 and 292 in COMBO and BT arms, respectively. The median age was 67 years; 89.1% had PSA < 10 ng/mL, 89.1% had GS 7, and 66.7% had T1 disease. There were no differences in FFP. The 5-year FFP-ASTRO was 85.6% (95% CI, 81.4 to 89.7) with COMBO compared with 82.7% (95% CI, 78.3 to 87.1) with BT (odds ratio [OR], 0.80; 95% CI, 0.51 to 1.26; Greenwood T P = .18). The 5-year FFP-Phoenix was 88.0% (95% CI, 84.2 to 91.9) with COMBO compared with 85.5% (95% CI, 81.3 to 89.6) with BT (OR, 0.80; 95% CI, 0.49 to 1.30; Greenwood T P = .19). There were no differences in the rates of genitourinary (GU) or GI acute toxicities. The 5-year cumulative incidence for late GU/GI grade 2+ toxicity is 42.8% (95% CI, 37.0 to 48.6) for COMBO compared with 25.8% (95% CI, 20.9 to 31.0) for BT (P < .0001). The 5-year cumulative incidence for late GU/GI grade 3+ toxicity is 8.2% (95% CI, 5.4 to 11.8) compared with 3.8% (95% CI, 2.0 to 6.5; P = .006). Compared with BT, COMBO did not improve FFP for prostate cancer but caused greater toxicity. BT alone can be considered as a standard treatment for men with intermediate-risk prostate cancer.

Hypofractionated Radiotherapy in Localized, Low-Intermediate-Risk Prostate Cancer: Current and Future Prospectives.

At the time of diagnosis, the vast majority of prostate carcinoma patients have a clinically localized form of the disease, with most of them presenting with low- or intermediate-risk prostate cancer. In this setting, various curative-intent alternatives are available, including surgery, external beam radiotherapy and brachytherapy. Randomized clinical trials have demonstrated that moderate hypofractionated radiotherapy can be considered as a valid alternative strategy for localized prostate cancer. High-dose-rate brachytherapy can be administered according to different schedules. Proton beam radiotherapy represents a promising strategy, but further studies are needed to make it more affordable and accessible. At the moment, new technologies such as MRI-guided radiotherapy remain in early stages, but their potential abilities are very promising.

Does cost minimization of hypofractionated radiation therapy content all health stakeholders?

Does cost minimization of hypofractionated radiation therapy content all health stakeholders?

Current Trends in Incidence and Management of T1a and T1b Prostate Cancer.

Prostate cancer (PCa) identified incidentally (iPCa) after surgical treatment for symptomatic benign prostatic hyperplasia (BPH) causing lower urinary tract symptoms (LUTS) is considered low risk by the most current guidelines. Management protocols for iPCa are conservative and are identical to other prostate cancers classified as having favorable prognoses. The objectives of this paper are to discuss the incidence of iPCa stratified by BPH procedure, to highlight predictors of cancer progression, and to propose potential modifications to mainstream guidelines for the optimal management of iPCa. The correlation between the rate of iPCa detection and the method of BPH surgery is not clearly defined. Old age, small prostate volume, and high pre-operative prostate-specific antigen (PSA) are associated with an increased likelihood of detecting iPCa. PSA and tumor grade are strong predictors of cancer progression and can be used along with magnetic resonance imaging (MRI) and potential confirmatory biopsies to determine disease management. In instances that iPCa requires treatment, radical prostatectomy (RP), radiation therapy, and androgen deprivation therapy all have oncologic benefits but may be associated with increased risk after the BPH surgery. It is advised that patients with low to favorable intermediate-risk prostate cancer undergo post-operative PSA measurement and prostate MRI imaging before electing to choose between observation, surveillance without confirmatory biopsy, immediate confirmatory biopsy, or active treatment. Subdividing the binary T1a/b cancer staging into more categories with ranging percentages of malignant tissue would be a helpful first step in tailoring the management of iPCa.

Biopsy Assessment of Oncologic Control 3 Years Following Primary Partial Gland Cryoablation: A Prospective Cohort Study of Men With Intermediate-risk Prostate Cancer.

We evaluated 3-year oncologic outcomes following primary partial gland cryoablation. Men with unilateral intermediate-risk prostate cancer undergoing primary partial gland cryoablation since March 2017 enrolled in a prospective outcome registry. The postablation protocol for all men included surveillance prostate biopsy at 2 years postablation and reflex prostate biopsy for cases with high suspicion of recurrence (eg, progressive rise in PSA). Recurrence of clinically significant prostate cancer was defined as any Gleason grade group ≥2 disease on postablation biopsy. Freedom from failure represented no whole gland salvage treatment, metastatic prostate cancer, or prostate cancer mortality. Freedom from recurrence and freedom from failure were characterized using nonparametric maximum likelihood estimators. A total of 132 men had at least 24 months of follow-up data. Biopsies identified clinically significant prostate cancer in 12 men. At 36 months, model-estimated rates of freedom from recurrence of in-field, out-of-field, and overall clinically significant cancer were 97% (95% CI: 92-100), 87% (95% CI: 80-94), and 86% (95% CI: 78-93), respectively. The model-estimated proportion with freedom from failure at 36 months was 97% (95% CI: 93-100). The low in-field cancer detection rate at 3 years indicates successful ablation of localized cancers. Conversely, our observed out-of-field detection rate highlights the need for continued surveillance following partial gland cryoablation. Many of these recurrences exhibited very low volume of clinically significant disease below the detection threshold of multiparametric MRI, suggesting a limited role for multiparametric MRI in detecting clinically significant recurrences at 2 years. These findings emphasize the need for long-term surveillance and identification of predictors of clinically significant prostate cancer recurrences to guide biopsy timing.