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Prostate Cancer and Prostatic Diseases Jun 2024Nearly one-third of patients with prostate cancer (PCa) experience biochemical recurrence (BCR) after primary definitive treatment. BCR increases the risk of distant... (Review)
Review
BACKGROUND
Nearly one-third of patients with prostate cancer (PCa) experience biochemical recurrence (BCR) after primary definitive treatment. BCR increases the risk of distant metastasis and mortality in patients with prognostically unfavorable features. These patients are best managed with a tailored treatment strategy incorporating risk stratification using clinicopathological factors, next-generation imaging, and genomic testing.
OBJECTIVE
This narrative review examines the utility of risk stratification for the management of patients with BCR in the context of clinical trial data, referencing the latest recommendations by European and US medical societies.
METHODS
PubMed was searched for relevant studies published through May 21 2023 on treatment of patients with BCR after radical prostatectomy (RP) or external beam radiotherapy (EBRT).
RESULTS
European and US guidelines support the risk-stratified management of BCR. Post-RP, salvage EBRT (with or without androgen deprivation therapy [ADT]) is an accepted treatment option for patients with BCR. Post-EBRT, local salvage therapies (RP, cryotherapy, high-intensity focused ultrasound, stereotactic body radiotherapy, and low-dose-rate and high-dose-rate brachytherapy) have demonstrated comparable relapse-free survival rates but differing adverse event profiles, short and long term. Local salvage therapies should be used for local-only relapses while ADT should be considered for regional or distant relapses. In practice, patients often receive ADT, with varying guidance for intermittent ADT vs. continuous ADT, due to consideration of quality-of-life effects.
CONCLUSIONS
Despite a lack of consensus for BCR treatment among guideline associations and medical societies, risk stratification of patients is essential for personalized treatment approaches, as it allows for an informed selection of therapeutic strategies and estimation of adverse events. In lower-risk disease, observation is recommended while in higher-risk disease, after failed repeat local therapy, ADT and/or clinical trial enrollment may be appropriate. Results from ongoing clinical studies of patients with BCR should provide consensus for management.
Topics: Humans; Male; Prostatic Neoplasms; Neoplasm Recurrence, Local; Risk Assessment; Prostatectomy; Prostate-Specific Antigen; Salvage Therapy; Prognosis; Androgen Antagonists
PubMed: 37679602
DOI: 10.1038/s41391-023-00712-z -
Lancet (London, England) Jun 2024Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial.
BACKGROUND
Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear.
METHODS
RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047.
FINDINGS
Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61-69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1-10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688-1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4-82·5) in the no ADT group and 80·4% (76·6-83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths.
INTERPRETATION
Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population.
FUNDING
Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society.
Topics: Humans; Male; Prostatic Neoplasms; Androgen Antagonists; Prostatectomy; Aged; Tosyl Compounds; Anilides; Middle Aged; Nitriles; Oligopeptides; Gonadotropin-Releasing Hormone; Combined Modality Therapy; Prostate-Specific Antigen
PubMed: 38763154
DOI: 10.1016/S0140-6736(24)00548-8 -
Journal of Robotic Surgery Oct 2023Urinary incontinence is one of the main concerns for patients after radical prostatectomy. Differences in surgical experience among surgeons could partly explain the... (Observational Study)
Observational Study
Urinary incontinence is one of the main concerns for patients after radical prostatectomy. Differences in surgical experience among surgeons could partly explain the wide range of frequencies observed. Our aim was to evaluate the association between the surgeons` experience and center caseload with relation to urinary continence recovery after Retzius-sparing robot-assisted radical prostatectomy (RS-RARP). Prospective observational single-center study. Five surgeons consecutively operated 405 patients between July 2017 and February 2022. Continence recovery was evaluated with pad count and by employing the short form of the International Consultation on Incontinence Questionnaire (ICIQ-SF), pre- and postoperatively at 1 year. Non-parametric tests were used. Median age was 63 years, 30% of patients presented with local advanced disease; the positive surgical margin rate (over 3 mm length) was 16%. Complication rate was 1% (Clavien-Dindo > II). One year after surgery, continence was assessed in 282 patients, of whom 87% were pad free and 51% never leaked (ICIQ-SF = 0). With respect to the mean annual number of procedures per surgeon, divided in < 20, 20-39 and ≥ 40, pad-free rates were achieved in 93%, 85%, and 84% and absence of urine leak rates in 47%, 62% and 48% of patients, respectively. Postoperative median ICIQ-SF was five. We acknowledge the limitation of a 12-month follow-up and the fact that we are a medium-volume center. There is no statistically significant association between continence recovery, surgeon's experience and center caseload. Continence recovery at 1 year after surgery is adequate and robust to surgeon's experience.
Topics: Male; Humans; Middle Aged; Robotic Surgical Procedures; Robotics; Prostate; Prostatectomy; Urinary Incontinence; Surgeons; Treatment Outcome
PubMed: 37528286
DOI: 10.1007/s11701-023-01687-8 -
Biomedicines Oct 2023Prostate cancer (PCa) is a low tumor mutational burden (TMB) cancer with a poor response to immunotherapy. Nonetheless, immunotherapy can be useful, especially in... (Review)
Review
Prostate cancer (PCa) is a low tumor mutational burden (TMB) cancer with a poor response to immunotherapy. Nonetheless, immunotherapy can be useful, especially in metastatic castration-resistant PCa (mCRPC). Increased cytotoxic T lymphocytes (CTLs) density is correlated with a shorter overall survival (OS), an early biochemical relapse, and a generally poor PCa prognosis. An increased number of CCR4+ regulatory T cells (CCR4 + Tregs) relates to a higher Gleason score or earlier progression. The same therapeutic options are available for renal transplant recipients (RTRs) as for the population, with a comparable functional and oncological outcome. Radical retropubic prostatectomy (RRP) is the most common method of radical treatment in RTRs. Brachytherapy and robot-assisted radical prostatectomy (RARP) seem to be promising therapies. Further studies are needed to assess the need for prostatectomy in low-risk patients before transplantation. The rate of adverse pathological features in RTRs does not seem to differ from those observed in the non-transplant population and the achieved cancer control seems comparable. The association between PCa and transplantation is not entirely clear. Some researchers indicate a possible association between a more frequent occurrence of PCa and a worse prognosis in advanced or metastatic PCa. However, others claim that the risk and survival prognosis is comparable to the non-transplant population.
PubMed: 38001942
DOI: 10.3390/biomedicines11112941 -
Frontiers in Surgery 2023Radical prostatectomy significantly impacts the inherent anatomy of the male pelvis and the functional mechanisms of urinary continence. Incontinence has a considerable... (Review)
Review
Radical prostatectomy significantly impacts the inherent anatomy of the male pelvis and the functional mechanisms of urinary continence. Incontinence has a considerable negative influence on the quality of life of patients, as well as their social and psychological wellbeing. Numerous surgical techniques have been demonstrated to support the preservation of continence during robot-assisted radical prostatectomy (RARP). In this in-depth analysis, we give a general summary of the surgical techniques used in RARP and their impact on incontinence rates.
PubMed: 38026481
DOI: 10.3389/fsurg.2023.1289765 -
The Journal of International Medical... Aug 2023Transurethral resection of the prostate (TURP) is the gold-standard classical method for the treatment of benign prostatic hyperplasia (BPH). In minimally invasive... (Meta-Analysis)
Meta-Analysis
Transurethral resection of the prostate (TURP) is the gold-standard classical method for the treatment of benign prostatic hyperplasia (BPH). In minimally invasive surgery, holmium laser enucleation of the prostate (HoLEP) is considered an alternative option. In this systematic review and meta-analysis, we aimed to comprehensively evaluate the advantages and disadvantages of TURP and HoLEP the treating BPH. We comprehensively searched PubMed, Cochrane Library, EMBASE, and Web of Science databases for all randomized controlled trials published before 1 December 2022 comparing HoLEP and TURP. The study protocol is registered on INPLASY (DOI: 10.37766/inplasy2023.5.0065). Compared with TURP, HoLEP required longer operation time but shorter catheter duration, hospital stay, and bladder irrigation time, as well as less postoperative irrigation. With HoLEP, maximum urinary flow rate at 12 and 24 months after surgery; post-void residual volume at 1, 6, and 12 months; and International Prostate Symptom Score at 12 months after surgery were superior to those with TURP. HoLEP was associated with significantly lower risk of hyponatremia, blood transfusion, and urethral stricture but greater risk of postoperative dysuria. Compared with TURP, HoLEP had better curative efficacy at 6, 12, and 24 months after operation and lower incidence of adverse events in patients with BPH.
Topics: Male; Humans; Prostate; Transurethral Resection of Prostate; Prostatic Hyperplasia; Lasers, Solid-State; Laser Therapy; Holmium; Treatment Outcome
PubMed: 37561537
DOI: 10.1177/03000605231190763 -
Journal of Robotic Surgery Dec 2023This study aims to conduct a systematic review of full economic analyses of robotic-assisted surgery (RAS) in adults' thoracic and abdominopelvic indications. Authors... (Review)
Review
This study aims to conduct a systematic review of full economic analyses of robotic-assisted surgery (RAS) in adults' thoracic and abdominopelvic indications. Authors used Medline, EMBASE, and PubMed to conduct a systematic review following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) 2020 guidelines. Fully published economic articles in English were included. Methodology and reporting quality were assessed using standardized tools. Majority of studies (28/33) were on oncology procedures. Radical prostatectomy was the most reported procedure (16/33). Twenty-eight studies used quality-adjusted life years, and five used complication rates as outcomes. Nine used primary and 24 studies used secondary data. All studies used modeling. In 81% of studies (27/33), RAS was cost-effective or potentially cost-effective compared to comparator procedures, including radical prostatectomy, nephrectomy, and cystectomy. Societal perspective, longer-term time-horizon, and larger volumes favored RAS. Cost-drivers were length of stay and equipment cost. From societal and payer perspectives, robotic-assisted surgery is a cost-effective strategy for thoracic and abdominopelvic procedures.Clinical trial registration This study is a systematic review with no intervention, not a clinical trial.
Topics: Male; Humans; Cost-Benefit Analysis; Robotic Surgical Procedures; Prostate; Prostatectomy; Quality-Adjusted Life Years
PubMed: 37843673
DOI: 10.1007/s11701-023-01731-7 -
Translational Andrology and Urology Jun 2023Erectile dysfunction (ED) is a prevalent and impactful complication post definitive management of prostate cancer. The mechanism of ED is thought to be secondary to... (Review)
Review
BACKGROUND AND OBJECTIVE
Erectile dysfunction (ED) is a prevalent and impactful complication post definitive management of prostate cancer. The mechanism of ED is thought to be secondary to vascular and neural injury as well as corporal smooth muscle damage with resultant fibrosis. The use of penile rehabilitation in ED following treatment for prostate cancer has been studied. Low-intensity extracorporeal shockwave therapy (Li-ESWT) is a novel treatment for ED thought to stimulate neovascularization and nerve regeneration, and as such, has gained interest in treatment of ED related to radical prostatectomy or radiation therapy. Herein, we performed a narrative review on the use of Li-ESWT in management of ED following treatment for prostate cancer.
METHODS
A literature review was performed using PubMed and Google Scholar. Studies evaluating Li-ESWT following prostate cancer treatment were included.
KEY CONTENT AND FINDINGS
We identified three randomized controlled trials and two observational studies that assessed use of Li-ESWT for ED after prostate surgery. Use of Li-ESWT across most studies showed improvements in the International Index of Erectile Function-erectile function (IIEF-EF) domain scores, but this improvement was not statistically significant. Additionally, use of Li-ESWT in an early versus delayed fashion does not appear to affect changes in long-term sexual function scores. No data on use of Li-ESWT after radiotherapy were identified.
CONCLUSIONS
There is a paucity of data regarding use of Li-ESWT for penile rehabilitation in treatment of ED post-prostate cancer therapy. Current protocols for Li-ESWT are not standardized and have a limited number of participants with short duration of follow-up. Additional evaluation is needed to determine optimal Li-ESWT protocols. Ideally, studies should have longer follow-up to truly evaluate the clinical significance of Li-ESWT in the treatment of post-prostatectomy ED. Furthermore, the role of Li-ESWT after radiotherapy remains elusive.
PubMed: 37426598
DOI: 10.21037/tau-22-791 -
Life (Basel, Switzerland) Jul 2023The optimal hypofractionated schedule of post-prostatectomy radiotherapy remains to be established. We evaluated treatment outcomes and toxicity of moderately...
BACKGROUND
The optimal hypofractionated schedule of post-prostatectomy radiotherapy remains to be established. We evaluated treatment outcomes and toxicity of moderately hypofractionated post-prostatectomy radiotherapy in 16 daily fractions delivered with intensity-modulated radiotherapy. The treatment schedule selection was motivated by limited technology resources and was radiobiologically dose-escalated.
METHODS
One hundred consecutive M0 patients with post-prostatectomy radiotherapy were evaluated. Radiotherapy indication was adjuvant (ART) in 19%, early-salvage (eSRT) in 46% and salvage (SRT) in 35%. The dose prescription for prostate bed planning target volume was 52.8 Gy in 16 fractions of 3.3 Gy. The Common Terminology Criteria v. 4 for Adverse Events scale was used for toxicity grading.
RESULTS
The median follow-up was 61 months. Five-year biochemical recurrence-free survival (bRFS) was 78.6%, distant metastases-free survival (DMFS) was 95.7% and overall survival was 98.8%. Treatment indication (ART or eSRT vs. SRT) was the only significant factor for bRFS (HR 0.15, 95% CI 0.05-0.47, = 0.001) and DMFS (HR 0.16, 95% CI 0.03-0.90; = 0.038). Acute gastrointestinal (GI) toxicity grade 2 was recorded in 24%, grade 3 in 2%, acute genitourinary (GU) toxicity grade 2 in 10% of patients, and no grade 3. A cumulative rate of late GI toxicity grade ≥ 2 was observed in 9% and late GU toxicity grade ≥ 2 in 16% of patients.
CONCLUSIONS
The observed results confirmed efficacy and showed a higher than anticipated rate of early GI, late GI, and GU toxicity of post-prostatectomy radiobiologically dose-escalated hypofractionated radiotherapy in 16 daily fractions.
PubMed: 37511985
DOI: 10.3390/life13071610 -
Prostate International Mar 2024Nomograms help to predict outcomes in individual patients rather than whole populations and are an important part of evaluation and treatment decision making. Various... (Review)
Review
Nomograms help to predict outcomes in individual patients rather than whole populations and are an important part of evaluation and treatment decision making. Various nomograms have been developed in malignancies to predict and prognosticate clinical outcomes such as severity of disease, overall survival, and recurrence-free survival. In prostate cancer, nomograms were developed for determining need for biopsy, disease course, need for adjuvant therapy, and outcomes. Most of these predictive nomograms were based on Caucasian populations. Prostate cancer is significantly affected by race, and Asian men have a significantly different racial and genetic susceptibility compared to Caucasians, raising the concern in generalizability of these nomograms. We reviewed the existing literature for nomograms in prostate cancer and their application in Asian men. There are very few studies that have evaluated the applicability and validity of the existing nomograms in these men. Most have found significant differences in the performance in this population. Thus, more studies evaluating the existing nomograms in Asian men or suggesting modifications for this population are required.
PubMed: 38523898
DOI: 10.1016/j.prnil.2023.07.004