Testosterone recovery after androgen deprivation therapy.

PURPOSE: Finite courses of androgen deprivation therapy (ADT) are often utilized in men undergoing treatment for prostate cancer. Previous evidence suggests that timing of testosterone (T) recovery can be variable after ADT. Recently, an oral gonadotropin releasing-hormone (GnRH) antagonist, relugolix, has demonstrated more rapid T recovery than injectable GnRH agonists such as leuprolide. In this study, we sought to evaluate patient characteristics associated with T recovery in patients undergoing ADT of defined duration. MATERIALS AND METHODS: The Northwestern Enterprise Data Warehouse was queried for men with prostate cancer who completed a course of ADT and subsequently had a testosterone lab performed. Testosterone recovery was evaluated for levels that reached above castrate (T > 50 ng/dl), partial recovery (T > 150 ng/dl), and full recovery (T ≥ 300 ng/dl). RESULTS: 388 men who received finite courses of ADT were identified (348 receiving leuprolide, 36 receiving relugolix, and 4 receiving degarelix). In multivariable Cox regression analysis, men who were prescribed GnRH antagonists (HR = 3.74, CI = 2.53-5.53, P ≤ 0.001) and who were younger (HR for 1 year increase in age = 0.96, CI = 0.95-0.98, P < 0.001) were more likely to achieve partial recovery. In a subgroup analysis, men who received extended ADT courses (>12 months) with a GnRH agonist had lower rates of partial T recovery (HR = 0.58, CI = 0.41-0.81, P = 0.001). CONCLUSION: T recovery after ADT is variable with roughly one sixth of men remaining castrate. GnRH antagonist use and younger age are associated with higher rates of T recovery after ADT. Longer ADT courses were associated with worse T recovery rates.

Utility of dynamic contrast enhancement for clinically significant prostate cancer detection.

Objective: This study aimed to evaluate the association of dynamic contrast enhancement (DCE) with clinically significant prostate cancer (csPCa, Gleason Grade Group ≥2) and compare biparametric magnetic resonance imaging (bpMRI) and multiparametric MRI (mpMRI) nomograms. Subjects/patients and methods: We identified a retrospective cohort of biopsy naïve patients who underwent pre-biopsy MRI separated by individual MRI series from 2018 to 2022. csPCa detection rates were calculated for patients with peripheral zone (PZ) lesions scored 3-5 on diffusion weighted imaging (DWI) with available DCE (annotated as - or +). bpMRI Prostate Imaging Reporting and Data System (PIRADS) (3 = 3-, 3+; 4 = 4-, 4+; 5 = 5-, 5+) and mpMRI PIRADS (3 = 3-; 4 = 3+, 4-, 4+; 5 = 5-, 5+) approaches were compared in multivariable logistic regression models. Nomograms for detection of csPCa and ≥GG3 PCa incorporating all biopsy naïve patients who underwent prostate MRI were generated based on available serum biomarkers [PHI, % free prostate-specific antigen (PSA), or total PSA] and validated with an independent cohort. Results: Patients (n = 1010) with highest PIRADS lesion in PZ were included in initial analysis with 127 (12.6%) classified as PIRADS 3+ (PIRADS 3 on bpMRI but PIRADS 4 on mpMRI). On multivariable analysis, PIRADS 3+ lesions were associated with higher csPCa rates compared to PIRADS 3- (3+ vs. 3-: OR 1.86, p = 0.024), but lower csPCa rates compared to PIRADS DWI 4 lesions (4 vs. 3+: OR 2.39, p < 0.001). csPCa rates were 19% (3-), 31% (3+), 41.5% (4-), 65.9% (4+), 62.5% (5-), and 92.3% (5+). bpMRI nomograms were non-inferior to mpMRI nomograms in the development (n = 1410) and independent validation (n = 353) cohorts. Risk calculators available at: https://rossnm1.shinyapps.io/MynMRIskCalculator/. Conclusion: While DCE positivity by itself was associated with csPCa among patients with highest PIRADS lesions in the PZ, nomogram comparisons suggest that there is no significant difference in performance of bpMRI and mpMRI. bpMRI may be considered as an alternative to mpMRI for prostate cancer evaluation in many situations.

Modern predictors and management of incidental prostate cancer at holmium enucleation of prostate.

BACKGROUND: To evaluate contemporary preoperative risk factors and subsequent postoperative management of incidental prostate cancer (iPCa) and incidental clinically significant prostate cancer (icsPCa, Grade Group [GG] ≥ 2 PCa). METHODS: A retrospective cohort of 811 men undergoing Holmium enucleation of the prostate (HoLEP) (January 2021-July 2022) were identified. Advanced preoperative testing was defined as prostate health index (PHI), prostate MRI, and/or negative preoperative biopsy. Descriptive statistics (Whitney-Mann U test, Chi-squared test) and multivariable logistic regression were performed. RESULTS: iPCa and icsPCa detection rates were 12.8% (104/811) and 4.4% (36/811), respectively. Advanced preoperative testing (406/811, 50%) was associated with younger age and higher (prostate specific antigen) PSA, prostate volume, and PSA density. On multivariable analysis, PHI ≥ 55 was associated with iPCa (OR 6.91, 95% CI 1.85-26.3, p = 0.004), and % free PSA (%fPSA) was associated with icsPCa (OR 0.83, 95% CI 0.67, 0.94, p = 0.01). GG1 disease comprised the majority of iPCa (65%, 68/104) with median 1% involvement. iPCa patients were followed with active surveillance (median follow up 9.3 months), with higher risk patients receiving prostate MRI and confirmatory biopsy. Three patients proceeded to radical prostatectomy or radiation. CONCLUSIONS: In the era of MRI and advanced biomarkers, the majority of iPCa following HoLEP is low volume GG1 suitable for active surveillance. A tentative follow-up strategy is proposed. Patients with PHI ≥ 55 or low %fPSA, even with negative prostate MRI, can consider preoperative prostate biopsy before HoLEP.

Do Prostate Imaging-Reporting and Data System (PIRADS) lesions predict holmium laser enucleation of prostate outcomes?

INTRODUCTION AND OBJECTIVES: Prostate magnetic resonance imaging (MRI) is used for prostate cancer (PCa) screening and risk stratification and is helpful for surgical planning for patients undergoing holmium laser enucleation of the prostate (HoLEP). There are few studies investigating the correlation between MRI Prostate Imaging-Reporting and Data System (PIRADS) lesion characteristics and HoLEP pathology and outcomes. METHODS: We performed retrospective review of patients who underwent HoLEP between January 2021 and August 2023 by a single surgeon. Preoperative, intraoperative, and postoperative characteristics and outcomes were analyzed for all patients who had a documented preoperative prostate MRI. RESULTS: There were 334 patients without a pre-existing diagnosis of PCa and with a preoperative prostate MRI, of which 140 (42%) had at least one PIRADS lesion. There was a total of 203 PIRADS lesions: 91 (45%) in the peripheral zone (PZ), 106 (52%) in the transition zone (TZ), and 6 (2%) not specified. Incidental PCa was noted in 44 (13%) patients at time of HoLEP. Presence or location of lesion was not significantly associated with rate or grade of incidental PCa on pathology. Greater number of lesions and lesion size correlated with longer procedure times. Lesion number, size, or grade were not found to correlate with cancer grade or rate of cancer. CONCLUSIONS: Grade, presence, location, size, and number of PIRADS lesions on preoperative prostate MRI for patients with an appropriate prior PCa workup were not significantly associated with incidental PCa or higher PCa grade on HoLEP pathology.

Detection of clinically significant prostate cancer following initial omission of biopsy in multiparametric MRI era.

BACKGROUND: Multiparametric prostate MRI (mpMRI) is being increasingly adopted for work-up of prostate cancer. For patients selected to omit biopsy, we identified factors associated with repeat MRI, eventual prostate biopsy, and subsequent detection of clinically significant prostate cancer (csPCa, Grade Group ≥2). METHODS: We identified biopsy-naïve men presenting with PSA 2-20 ng/mL (March 2018-June 2021) undergoing initial mpMRI with PIRADS 1-3 lesions who were not selected for biopsy with ≥6 months follow-up. We examined factors associated with repeat mpMRI, progression to biopsy, and subsequent detection of csPCa with univariable and multivariable logistic regression. RESULTS: Of 1494 men, 31% (463/1494) did not pursue biopsy. PSA density (PSAD) ≤ 0.1, prostate health index (PHI) < 55, and PIRADS 1-2 were associated with omission of prostate biopsy. csPCa diagnosis-free survival was 97.6% (326/334) with median follow up of 23.1 months (IQR 15.1-34.6 months). Black race, PSA, PHI, PSA density, and PSA and PHI velocity were significant predictors of undergoing repeat mpMRI (15.6%, 52/334) and subsequent biopsy (8.4%, 28/334). 8 men were subsequently diagnosed with csPCa (N = 7 on prostate biopsy; N = 1 incidentally on holmium enucleation of prostate). All patients diagnosed with csPCa had PIRADS 4-5 on repeat mpMRI. CONCLUSIONS: The subsequent detection rate of csPCa among patients not initially biopsied after mpMRI was low at 2.4%. Decisions to omit biopsy after initial reassuring PHI, PSAD, and mpMRI appear safe with subsequent reassuring serum biomarkers and for cause mpMRI during follow-up.

Contemporary Diagnosis of Very Low-risk Prostate Cancer in a Multihospital Health Care System.

The National Comprehensive Cancer Network (NCCN) very low risk (VLR) category for prostate cancer (PCa) represents clinically insignificant disease, and detection of VLR PCa contributes to overdiagnosis. Greater use of magnetic resonance imaging (MRI) and biomarkers before patient selection for prostate biopsy (PBx) reduces unnecessary biopsies and may reduce the diagnosis of clinically insignificant PCa. We tested a hypothesis that the proportion of VLR diagnoses has decreased with greater use of MRI-informed PBx using data from our 11-hospital system. From 2018 to 2023, 351/3197 (11%) men diagnosed with PCa met the NCCN VLR criteria. The proportion of VLR diagnoses did not change from 2018 to 2023 (p = 0.8) despite an increase in the use of MRI-informed PBx (from 49% to 82%; p < 0.001). Of patients who underwent combined systematic and targeted PBx and were diagnosed with VLR disease, cancer was found in systematic PBx regions in 79% of cases and in targeted PBx regions in 31% of cases. When performing both systematic and targeted PBx, prebiopsy MRI-based risk calculators could limit VLR diagnosis by 41% using a risk threshold of >5% for Gleason grade group ≥3 PCa to recommend biopsy; the reduction would be 77% if performing targeted PBx only. These findings suggest that VLR disease continues to account for a significant minority of PCa diagnoses and could be limited by targeted PBx and risk stratification calculators. PATIENT SUMMARY: We looked at recent trends for the diagnosis of very low-risk (VLR) prostate cancer. We found that VLR cancer still seems to be frequently diagnosed despite the use of MRI (magnetic resonance imaging) scans before biopsy. The use of risk calculators to identify men who could avoid biopsy and/or biopsy only for lesions that are visible on MRI could reduce the overdiagnosis of VLR prostate cancer.

Ultrasensitive PSA: rethinking post-surgical management for node positive prostate cancer.

Introduction: Clinicians may offer patients with positive lymph nodes (pN1) and undetectable PSA following surgery for prostate cancer either observation or adjuvant therapy based on AUA, EAU, and NCCN guidelines considering standard PSA detection thresholds of <0.1ng/ml. Here we sought to investigate the outcomes of pN1 patients in the era of ultrasensitive PSA testing. Methods: We queried the Northwestern Electronic Data Warehouse for patients with prostate cancer who were pN1 at radical prostatectomy and followed with ultrasensitive PSA. Patients receiving neoadjuvant treatment were excluded. We compared clinical characteristics including age, race, pre-operative PSA, Gleason grade, tumor stage, surgical margins, and nodal specimens to identify factors associated with achievement and maintenance of an undetectable PSA (defined as <0.01 ng/mL). Statistics were performed using t-test, Mann-Whitney U test, chi-squared analysis, and logistic regression with significance defined as p<0.05. Results: From 2018-2023, 188 patients were included. Subsequently, 39 (20.7%) had a PSA decline to undetectable levels (<0.01 ng/mL) post-operatively at a median time of 63 days. Seven percent of these men (3/39) were treated with adjuvant RT + ADT with undetectable PSA levels. 13/39 (33.3%) had eventual rises in PSA to ≥0.01 ng/mL for which they underwent salvage RT with ADT. Overall, 23/39 (59%) patients achieved and maintained undetectable PSA levels without subsequent therapy at median follow-up of 24.2 mo. Compared to patients with PSA persistence after surgery or elevations to detectable levels (≥0.01 ng/mL), patients who achieved and maintained undetectable levels had lower Gleason grades (p=0.03), lower tumor stage (p<0.001), fewer positive margins (p=0.02), and fewer involved lymph nodes (p=0.02). On multivariable analysis, only primary tumor (pT) stage was associated with achieving and maintaining an undetectable PSA; pT3b disease was associated with a 6.6-fold increased chance of developing a detectable PSA (p=0.03). Conclusion: Ultrasensitive PSA can aid initiation of early salvage therapy for lymph node positive patients after radical prostatectomy while avoiding overtreatment in a significant subset. 20% of patients achieved an undetectable PSA and over half of this subset remained undetectable after 2 years.

Implementation of PSMA PET/CT and alignment of ordering to SNMMI appropriate use criteria in a large network system.

INTRODUCTION: The Society of Nuclear Medicine and Molecular Imaging (SNMMI) provides appropriate use criteria (AUC) for prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) which include guidance on imaging in newly diagnosed prostate cancer and in patients with biochemically recurrent (BCR) disease. This study aims to examine trends in PSMA implementation and the prevalence and outcomes of scans ordered in scenarios deemed rarely appropriate or not meeting SNMMI AUC. METHODS: We retrospectively identified patients who were diagnosed with presumptive National Comprehensive Cancer Network unfavorable intermediate, high, or very high risk prostate cancer, patients who underwent staging for BCR, and all patients staged with PSMA between July 2021 and March 2023. Positivity was validated by adherence to a predetermined reference standard. RESULTS: The frequency of PSMA use increased in initial staging from 24% to 80% and work-up of BCR from 91% to 99% over our study period. In addition, 5% (17/340) of PSMA scans ordered for initial staging did not meet AUC and 3% (15/557) of posttreatment scans were deemed rarely appropriate. Initial staging orders not meeting SNMMI AUC resulted in no positivity (0/17), while rarely appropriate posttreatment scans were falsely positive in 75% (3/4) of cases. Urologists (53%, 17/32) comprised the largest ordering specialty in rarely appropriate use. CONCLUSION: The frequency of PSMA use rose across the study period. A significant minority of patients received PSMA PET/CT in rarely appropriate scenarios yielding no positivity in initial staging and significant false positivity post-therapy. Further education of providers and electronic medical record-based interventions could help limit the rarely appropriate use of PET imaging.

'THIS IS NO COUNTRY FOR OLD (WO)MEN'? AN EXAMINATION OF THE APPROACH TAKEN TO CARE HOME RESIDENTS DURING THE COVID-19 PANDEMIC.

This article discusses the human rights of residents in care homes in England who were affected by restrictions that were imposed during the first months of the COVID-19 pandemic in order to safeguard health and life at a time of public health emergency. It focuses on the potentially adversarial relationship between the need to protect the health of these residents and the possible adverse interferences with their human rights in the initial phase of the pandemic. The scope and application of these rights to the healthcare context is not straightforward due to the exigencies of the pandemic. Consideration is given to whether their rights, as protected by the European Convention on Human Rights (ECHR) and the United Nations Convention on the Rights of Persons with Disabilities (CRPD) are vindicated or breached by the actions taken in the context of the COVID-19 pandemic. The article questions whether the restrictions that were applied were justified, given the limitations that exist within some ECHR Articles. It deliberates upon what can be done to ensure that relevant bodies and care homes, themselves, are better enabled to respond to a public health emergency in an individualistic, rights-based manner, based upon both principlism and pragmatism.

COVID-19 Vaccination and Legal Preparedness: Lessons from Ireland.

Ireland has been a leader in the COVID-19 vaccine rollout in the EU, with almost 80% of the eligible population (aged over 5 years) fully vaccinated at the time of writing. The success of the vaccine rollout in this jurisdiction notwithstanding, the legal frameworks supporting the rollout had significant lacunas. Two aspects in particular highlighted a lack of legal preparedness: the inadequacy of the legal framework for consent and the absence of a vaccine injury redress scheme. This paper explores these components of the COVID-19 vaccine rollout through the lens of legal preparedness. Whilst most often discussed in the context of command and control measures such as social distancing requirements and regional lockdowns, this paper argues for an expanded understanding of what it means to be legally prepared, highlighting the importance of the preparedness of domestic legal frameworks.

Re H (A Child) (Parental Responsibility: Vaccination): The Merits of Adopting A Softer Approach To Vaccination of A Child in Care?

In Re H (A Child) (Parental Responsibility: Vaccination), the Court of Appeal decided that vaccination did not represent 'grave' or 'serious' medical treatment and determined that, in the case of a child under the care of a Local Authority, court authorization for consent to and arrangement of vaccination is no longer required. This is due to the strong medical evidence in support of vaccination. Thus, with due reference to 33(3)(b) Children Act 1989 and while considering proportionality and, particularly, the proportionate response to interference with the parents' right to respect for private and family life under Article 8 of the European Convention on Human Rights, the court held that vaccination is in line with the best interests of the child. This commentary supports this judgment but identifies a slight prospective anomaly in the approach adopted to children in care and those who are not in care. The resolution of this dichotomy lies in broadening the scope of King LJ's approach in this case.