Adjuvant immune checkpoint inhibitors for urothelial carcinoma: systematic review and Meta-analysis.

PURPOSE: To compare disease-free survival (DFS), overall survival (OS), and adverse events (AEs) among muscle-invasive urothelial carcinoma (MIUC) patients receiving adjuvant immune checkpoint inhibitors (ICIs) versus placebo/observation following radical surgery. METHODS: This was a systematic review/meta-analysis of all published phase 3 randomized controlled trials. MEDLINE, EMBASE, and Cochrane were searched from inception until April 4, 2024. Pooled hazard ratios (HR) and relative risks (RR), plus confidence intervals (CI), were generated using frequentist random-effects modeling. RESULTS: Three trials were identified: IMvigor010, CheckMate 274, and AMBASSADOR. In the overall cohort, adjuvant ICIs significantly improved DFS by 23% (HR = 0.77, 95% CI = 0.65-0.90). No DFS benefit was observed in patients with upper tract disease (HR = 1.19, 95% CI = 0.86-1.64). The highest magnitude of DFS benefit was observed among patients who had received prior neoadjuvant chemotherapy (HR = 0.69) and pathologic node-positive disease (HR = 0.75). A similar DFS benefit was observed irrespective of tumor PD-L1 status. Pooled OS demonstrated a 13% non-significant benefit (HR = 0.87, 95% CI = 0.75-1.01). Grade ≥ 3 immune-mediated AEs occurred in 8.6% and 2.1% of ICI and placebo/observation patients, respectively (RR = 4.35, 95% CI = 1.02-18.5). AEs leading to treatment discontinuation occurred in 14.3% and 0.9% of patients, respectively. CONCLUSION: Adjuvant ICIs confer a DFS benefit following radical surgery for MIUC, particularly among node-positive patients and those who received prior neoadjuvant chemotherapy. The lack of benefit for upper tract disease suggests that alternate adjuvant approaches, including chemotherapy, should be considered for these patients. Tumor PD-L1 status is not a predictive biomarker, highlighting the need for biomarkers in this setting.

Hysterectomy versus chemotherapy for low-risk non-metastatic gestational trophoblastic neoplasia (GTN): A cost-effectiveness analysis.

OBJECTIVE: Determine the cost-effectiveness for hysterectomy versus standard of care single agent chemotherapy for low-risk gestational trophoblastic neoplasia (GTN). METHODS: A cost-effectiveness analysis was conducted comparing single agent chemotherapy with hysterectomy using decision analysis and Markov modeling from a healthcare payer perspective in Canada. The base case was a 40-year-old patient with low-risk non-metastatic GTN that completed childbearing. Outcomes were life years (LYs), quality-adjusted life years (QALYs), incremental cost-effectiveness ratio (ICER), and adjusted 2022 costs (CAD). Discounting was 1.5% annually and the time horizon was the patient's lifetime. Model validation included face validity, deterministic sensitivity analyses, and scenario analysis. RESULTS: Mean costs for chemotherapy and hysterectomy arms were $34,507 and $17,363, respectively, while effectiveness measure were 30.37 QALYs and 31.04 LYs versus 30.14 QALYs and 30.82 Lys, respectively. The ICER was $74,526 (USD $54,516) per QALY. Thresholds favoring hysterectomy effectiveness were 30-day hysterectomy mortality below 0.2% and recurrence risk during surveillance above 9.2% (low-risk) and 33.4% (high-risk). Scenario analyses for Dactinomycin and Methotrexate led to similar results. Sensitivity analysis using tornado analysis found the cost to be most influenced by single agent chemotherapy cost and risk of resistance, number of weeks of chemotherapy, and probability of postoperative mortality. CONCLUSION: Compared to hysterectomy, single agent chemotherapy as a first-line treatment costs $74,526 for each additional QALY gained. Given that this cost falls below the accepted $100,000 willingness-to-pay threshold and waitlist limitations within public healthcare systems, these results support the continued use of chemotherapy as standard of care approach for low-risk GTN.

Association of extended core sampling with delayed intervention and pathologic outcomes for active surveillance patients A population-based analysis.

INTRODUCTION: Combined systematic plus targeted biopsy sampling improves detection of clinically significant prostate cancer (PCa). Our objective was to evaluate whether extended core sampling at initial biopsy in active surveillance (AS) patients is associated with subsequent AS discontinuation and pathologic outcomes. METHODS: National Comprehensive Cancer Network (NCCN) low- and favorable-intermediate-risk (FIR) AS patients diagnosed between 2010 and 2015 were identified from the Surveillance, Epidemiology, and End Results (SEER) Prostate with Watchful Waiting database. Prostate biopsy sampling was operationalized as: standard (10-12 cores), extended (13-20 cores), or super-extended (21+ cores). Sensitivity analyses using differing cutoffs was performed. Outcomes included delayed definitive intervention (radical prostatectomy [RP]/radiotherapy) and pathologic upgrading and/or downgrading in delayed RP patients. Multivariable logistic regression modelling adjusted for sociodemographic/oncologic variables was performed. RESULTS: This cohort included 42 459 patients (low-risk: 28 411; FIR:14 048); 25-29% and 3-5% of patients underwent extended and super-extended core sampling, respectively, at diagnosis. Extended core sampling was associated with decreased odds of definitive intervention in low (odds ratio [OR] 0.89, p=0.003) and grade group 2 (GG2) FIR (OR 0.83, p=0.002) patients. Super-extended sampling was associated with decreased odds of definitive intervention in prostate-specific antigen (PSA) 10-20 FIR patients (OR 0.65, p=0.02). Super-extended sampling was associated with decreased odds of upgrading to ≥GG2 disease in low-risk (OR 0.45, p=0.032) and to ≥GG3 disease in GG2 FIR patients (OR 0.67, p=0.044). CONCLUSIONS: This population-based analysis demonstrates that extended/super-extended sampling at diagnosis is associated with significantly decreased odds of AS discontinuation and pathologic upgrading in low/FIR AS patients. This highlights the significance of extended tissue sampling at initial biopsy to appropriately risk-stratify AS patients and minimize AS discontinuation rates.

Intraductal Prostate Cancer Affinity for Lymphatic-Predominant Metastases Through 18F-DCFPyL‒Prostate-Specific Membrane Antigen‒Positron Emission Tomography/CT Scans in Pretreatment Prostate Cancer Patients.

PURPOSE: Intraductal prostate cancer (IDC) is linked to unfavorable oncologic outcomes, marked by distinctive cellular intrinsic pathway changes and intricate immunosuppressive microenvironments that could impact the way cancer spreads. The aim of this study was to determine whether the presence of IDC in prostate biopsy specimens obtained from patients before primary prostate cancer (PCa) treatment is associated with a lymph node metastatic propensity in prostate-specific membrane antigen (PSMA)‒positron emission tomography (PET)/CT. MATERIALS AND METHODS: This was a cross-sectional analysis of all PCa patients undergoing a pretreatment 18F-DCFPyL-PSMA-PET/CT between January 1, 2016, and August 2021 at The Princess Margaret Cancer Centre. Outcomes were presence of any metastasis in the overall cohort, presence of lymphatic vs no metastases, and presence of lymphatic vs bone metastasis among patients who underwent PSMA-PET/CT as PCa primary staging. The associations between IDC presence on the prostate biopsy and the study outcomes were evaluated using univariable and multivariable logistic regression analyses. RESULTS: The cohort consisted of 120 patients. IDC and cribriform pattern were observed in 55 (46%) and 48 (40%) prostate biopsies, respectively. Overall, 52 patients (43%) had evidence of metastasis. Presence of IDC on biopsy was associated with increased odds of overall metastasis (odds ratio: 2.47, 95% CI: 1.09-5.61, P = .03). Of the 52 patients with evidence of metastasis, 41 (79%) had evidence of lymphatic metastasis. Presence of IDC on biopsy was associated with significantly increased odds of lymphatic metastasis vs nonmetastases (odds ratio: 3.03, 95% CI: 1.24-7.40, P = .01). CONCLUSIONS: The identification of IDC morphology in prostate biopsy specimens has been observed to be significantly linked with lymph node metastasis on 18F-DCFPyL-PET/CT imaging in a PCa pretreatment staging setting. We found that presence of IDC in prostate biopsy appears to be a marker for lymph node metastasis on 18F-DCFPyL-PET/CT.

Using active surveillance for Gleason 7 (3+4) prostate cancer: A narrative review.

The interest in broadening the application of active surveillance (AS) has been increasing, encompassing patients who may not strictly adhere to the conventional criteria for low-risk prostate cancer (PCa), particularly those diagnosed with small-volume Gleason grade group 2 disease. Nonetheless, accurately identifying individuals with low intermediate-risk PCa who can safely undergo AS without facing disease progression remains a challenge.This review aims to delve into the progression of this evolving trend specifically within this cohort of men, while also examining strategies aimed at minimizing irreversible disease advancement. Additionally, we address the criteria for patient selection, recommended followup schedules, and the indicators prompting intervention.

Limitations of Prostate Biopsy in Detection of Cribriform and Intraductal Prostate Cancer.

BACKGROUND: The presence of cribriform morphology and intraductal carcinoma (IDC) in prostate biopsies and radical prostatectomy specimens is an adverse prognostic feature that can be used to guide treatment decisions. OBJECTIVE: To assess how accurately biopsies can detect cribriform morphology and IDC cancer by examining matched biopsy and prostatectomy samples. DESIGN, SETTING, AND PARTICIPANTS: Patients who underwent radical prostatectomy at The Princess Margaret Cancer Centre between January 2015 and December 2022 and had cribriform morphology and/or IDC in the surgical specimen were included in the study. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We used detection sensitivity to evaluate the level of agreement between biopsy and prostatectomy samples regarding the presence of cribriform morphology and IDC. RESULTS AND LIMITATIONS: Of the 287 men who underwent radical prostatectomy, 241 (84%) had cribriform morphology and 161 (56%) had IDC on final pathology. The sensitivity of prostate biopsy, using radical prostatectomy as the reference, was 42.4% (95% confidence interval [CI] 36-49%) for detection of cribriform morphology and 44.1% (95% CI 36-52%) for detection of IDC. The sensitivity of prostate biopsy for detection of either IDC or cribriform morphology was 52.5% (95% CI 47-58%). Among patients who underwent multiparametric magnetic resonance imaging-guided biopsies, the sensitivity was 54% (95% CI 39-68%) for detection of cribriform morphology and 37% (95% CI 19-58%) for detection of IDC. CONCLUSIONS: Biopsy has low sensitivity for detecting cribriform morphology and IDC. These limitations should be incorporated into clinical decision-making. Biomarkers for better detection of these histological patterns are needed. PATIENT SUMMARY: Prostate biopsy is not an accurate method for detecting two specific types of prostate cancer cells, called cribriform pattern and intraductal prostate cancer, which are associated with unfavorable prognosis.

Mesorectal nodal metastasis with seminal vesicle invasion in biochemically recurrent prostate cancer.

OBJECTIVES: To determine the prevalence and predictors of mesorectal lymph node (MLN) metastases on prostate-specific membrane antigen (PSMA)-based positron emission tomography/computed tomography (PET/CT) in patients with biochemically recurrent prostate cancer (PCa) following radical therapy. MATERIALS AND METHODS: This was a cross-sectional analysis of all PCa patients with biochemical failure following radical prostatectomy or radiotherapy who underwent an 18 F-DCFPyL-PSMA-PET/CT at the Princess Margaret Cancer Centre between December 2018 and February 2021. Lesions with PSMA scores ≥2 were considered positive for PCa involvement (PROMISE classification). Predictors of MLN metastasis were evaluated using univariable and multivariable logistic regression analyses. RESULTS: Our cohort consisted of 686 patients. The primary treatment method was radical prostatectomy and radiotherapy in 528 (77.0%) and 158 patients (23.0%), respectively. The median serum PSA level was 1.15 ng/mL. Overall, 384 patients (56.0%) had a positive scan. Seventy-eight patients (11.3%) had MLN metastasis, with 48/78 (61.5%) having MLN involvement as the only site of metastasis. On multivariable analysis, presence of pT3b disease (odds ratio 4.31, 95% confidence interval 1.44-14.2; P = 0.011) was significantly associated with increased odds of MLN metastasis, whereas surgical factors (radical prostatectomy vs radiotherapy; performance/extent of pelvic nodal dissection), surgical margin positivity, and Gleason Grade were not. CONCLUSIONS: In this study, 11.3% of PCa patients with biochemical failure had MLN metastasis on 18 F-DCFPyL-PET/CT. pT3b disease was associated with 4.31-fold significantly increased odds of MLN metastasis. These findings suggest alternate drainage routes for PCa cells, either via alternate lymphatic drainage from the seminal vesicles themselves or secondary to direct extension from posteriorly located tumours invading the seminal vesicles.

Neoadjuvant Cabazitaxel plus Abiraterone/Leuprolide Acetate in Patients with High-Risk Prostate Cancer: ACDC-RP Phase II Trial.

PURPOSE: Early treatment intensification with neoadjuvant therapy may improve outcomes in patients with high-risk, localized prostate cancer treated with radical prostatectomy. Our objective was to compare pathologic, oncologic, and safety outcomes of neoadjuvant abiraterone acetate plus leuprolide acetate with or without cabazitaxel prior to radical prostatectomy in patients with localized, high-risk prostate cancer. PATIENTS AND METHODS: This open-label, multicenter, phase II trial randomized men with clinically localized, D'Amico high-risk prostate cancer to neoadjuvant abiraterone acetate (1,000 mg/day) and leuprolide acetate (22.5 mg every 3 months) with or without cabazitaxel (25 mg/m2) prior to radical prostatectomy. The primary outcome was pathologic complete response (pCR) or minimal residual disease (MRD). Secondary outcomes included surgical margins, lymph node involvement, pathologic stage, 12-month biochemical relapse-free survival (BRFS) rates, and safety profile. RESULTS: The per-protocol population consisted of 70 patients [cabazitaxel arm (Arm A): 37, no cabazitaxel arm (Arm B): 33]. Median patient age and prostate-specific antigen levels were 63.5 years [interquartile range (IQR), 58.0-68.0] and 21.9 ng/mL (IQR, 14.6-42.8), respectively. pCR/MRD occurred in 16 (43.2%) versus 15 patients (45.5%) in arms A and B, respectively (P = 0.85). pCR occurred in two (5.4%) versus three patients (9.1%) in arms A and B, respectively (P = 0.66). Patients with ≤ 25% total biopsy cores positive had increased odds of pCR/MRD (P = 0.04). Patients with pCR/MRD had superior 12-month BRFS rates (96.0% vs. 62.0%, P = 0.03). Grade 3+ adverse events occurred in 42.5% and 23.7% of patients in arms A and B, respectively (P = 0.078). CONCLUSIONS: Neoadjuvant cabazitaxel addition to abiraterone acetate/leuprolide acetate prior to radical prostatectomy did not improve pCR/MRD in clinically localized, high-risk prostate cancer.

Poly(adenosine diphosphate-ribose) polymerase inhibitor combinations in first-line metastatic castrate-resistant prostate cancer setting: a systematic review and meta-analysis.

OBJECTIVES: To compare radiographic progression-free survival (rPFS), overall survival (OS), and treatment-emergent adverse events (TEAEs) among patients with metastatic castrate-resistant prostate cancer (mCRPC) receiving a combination of first-line poly(adenosine diphosphate-ribose) polymerase inhibitors (PARPi) plus androgen receptor axis-targeted agents (ARAT) vs placebo/ARAT. MATERIALS AND METHODS: We conducted a systematic review/meta-analysis of all published Phase III randomised controlled trials using EMBASE, MEDLINE, and Cochrane (inception until 6 June 2023). Published full-text manuscripts and conference abstracts were inclusion eligible. Study selection/data extraction were independently performed by two authors. The Cochrane Risk-of-Bias 2 Tool was used, and certainty of evidence assessed using the Grading of Recommendations, Assessment, Development, and Evaluations framework. Pooled hazard ratios (HRs) and relative risks, with corresponding confidence intervals (CIs), were generated using random-effects models. RESULTS: Three trials were identified: PROpel, MAGNITUDE, and TALAPRO-2. Compared to placebo/ARAT, the PARPi/ARAT combination was associated with a 35% rPFS improvement in the overall cohort (HR 0.65, 95% CI 0.56-0.76), with 68%, 45%, and 26% improvements in the BReast CAncer gene 1/gene 2 (BRCA1/2)-mutated (BRCA1/2m; P < 0.001), homologous recombination repair-mutated (HRRm; P < 0.001), and non-HRRm cohorts (P = 0.003), respectively. OS data maturity ranged from 31% to 48%, with overall cohort OS data unavailable from MAGNITUDE. The PROpel/TALAPRO-2 pooled analysis demonstrated a 16% OS improvement in the overall cohort (HR 0.84, 95 CI 0.72-0.98; P = 0.02). OS in the HRRm (HR 0.76, 95% CI 0.61-0.95) and the BRCA1/2m cohorts (HR 0.53, 95% CI 0.18-1.56) were improved, with a higher effect magnitude compared to the overall cohort. This combination was associated with a 45% relative risk increase in Grade ≥3 TEAEs, including 6.22-fold for Grade ≥3 anaemia (31.9% vs 4.9%). CONCLUSIONS: The addition of PARPi to ARAT in the first-line mCRPC setting is associated with rPFS benefits across subgroups, with the greatest magnitude of benefit in BRCA1/2m patients. OS benefits remain inconsistent irrespective of HRRm status, with significant increases in Grade ≥3 TEAEs, particularly anaemia. Currently, we suggest this combined approach be selectively offered to HRRm patients, preferentially BRCA1/2m.

Lymphotropic Pattern of Prostate-specific Membrane Antigen-detected Metastases Among Biochemically Recurrent Radical Prostatectomy Patients with Cribriform Disease.

BACKGROUND: Cribriform morphology portends worse oncologic outcomes, and has unique cellular intrinsic pathway alterations and tumor microenvironments that may impact metastatic spread patterns. OBJECTIVE: To determine whether the presence of cribriform morphology in prostatectomy specimens of patients with biochemical recurrence after radical prostatectomy (RP) is associated with the presence of metastasis on prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) and a distinct pattern of spread. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional analysis was conducted of all prostate cancer patients with biochemical recurrence after RP undergoing 18F-DCFPyL-PET/CT between December 2018 and February 2021 at the Princess Margaret Cancer Centre. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Outcomes were presence of any metastasis in the overall cohort and lymphatic versus bone/visceral metastases among patients with metastatic disease. The associations between the presence of intraductal (IDC) and/or invasive cribriform (ICC) carcinoma on the RP specimen and study outcomes were evaluated using logistic regression analyses. RESULTS AND LIMITATIONS: The cohort included 176 patients. IDC and ICC were observed in 77 (43.8%) and 80 (45.5%) RP specimens, respectively. The median time from RP to PSMA-PET/CT was 5.0 yr. The median serum prostate-specific antigen level at PSMA-PET/CT was 1.12 ng/ml. Overall, metastasis was observed in 77 patients, of whom 58 were had lymphatic-only metastasis. On a multivariable analysis, presence of IDC on RP was associated with increased odds of overall metastasis (odds ratio [OR]: 2.17; 95% confidence interval [CI]: 1.07-4.45; p = 0.033). Presence of ICC on RP was associated with significantly increased odds of lymphatic versus bone/visceral metastases (OR: 3.13; 95% CI: 1.09-21.7; p = 0.004). CONCLUSIONS: Presence of cribriform morphology on RP specimens of patients with biochemical failure after RP is associated with increased odds of PSMA-PET/CT-detected metastases with a lymphatic predominant pattern of spread. These findings have implications for the design and evaluation of post-RP salvage therapies. PATIENT SUMMARY: We found that microscopic cribriform appearance correlates with disease spread on imaging in prostate cancer patients with recurrence and has a predilection for spread to lymph nodes, as opposed to bone or visceral organs.

Small Renal Masses: The Evolving Histologic, Imaging, and Genomic Landscapes.

According to the American Cancer Society, it is currently estimated that approximately 81,800 new cases of kidney cancer will be diagnosed in the United States in 2023 [...].

Urologic Oncology Survivorship Guidelines: An Overview of the Evidence and the Current Implementation Gap.

Cancer survivorship is particularly significant for patients with urologic malignancies, who account for >25% of cancer survivors. The American Cancer Society has a guideline on survivorship care in prostate cancer and the American Urological Association has published a core curriculum on cancer survivorship in urologic cancers. However, there is a lack of high-quality evidence on survivorship strategies to inform guideline recommendations. Future efforts need to focus on producing high-quality survivorship research and on increasing appropriate resources to improve the implementation of survivorship care. PATIENT SUMMARY: There are few guidelines on survivorship care for patients with prostate, bladder, penile, or kidney cancer. More funding is needed for research into care for cancer survivors.

Pudendal nerve block prior to inflatable penile prosthesis implantation: decreased intra-operative narcotic requirements.

The opioid epidemic has proven to be a public health crisis over the past two decades and efforts to decrease opioid exposure are sorely needed. Our objective was to determine whether pudendal nerve block utilization in the immediate pre-operative setting decreases intra-operative opioid analgesic requirements in veteran patients undergoing a primary inflatable penile prosthesis implantation. We performed a retrospective cohort analysis of all patients undergoing penile prosthesis implantation between January 2017 and July 2020 at the Charlie Norwood Veterans Affairs Medical Center in Augusta, GA. Univariable and multivariable gamma regression analyses were performed to evaluate the association between pudendal nerve block utilization and intra-operative opioid analgesic requirements. The study cohort consisted of 110 patients, 35 (31.8%) of whom underwent a pudendal nerve block. Median intra-operative opioid analgesic requirements were significantly lower in the pudendal nerve block group (16.3 versus 25.8 morphine milliequivalents, p = 0.037). Receipt of the nerve block was associated with significantly lower intra-operative opioid analgesic requirements on multivariable (coefficient 0.84, p = 0.038) regression analysis. There was no significant difference in post-operative opioid analgesic requirements (p = 0.18). In conclusion, pre-operative pudendal nerve blocks decrease intra-operative opioid analgesic requirements in veteran patients undergoing a primary inflatable penile prosthesis implantation.