Transitioning from transrectal to transperineal prostate biopsy using a freehand cognitive approach.

OBJECTIVES: To report a single-centre experience of a complete transition from transrectal (TR) to transperineal (TP) prostate biopsy under local anaesthesia using a freehand cognitive coaxial approach and without use of antibiotic prophylaxis. PATIENTS AND METHODS: Analysis was performed of a prospective database of patients undergoing prostate biopsy performed by four surgeons between 1 June 2018 and 31 May 2022. Outcomes of interest were complications, cancer detection rate, inter-operator reliability, and tolerability. RESULTS: Overall, 1915 patients underwent 2337 separate prostate biopsy sessions. Only 2.4% patients in the TP group received antibiotic prophylaxis, while 100% received antibiotics in the TR group. The complication rate was significantly lower in the TP group compared to the TR group (0.3% vs 5.0%, P < 0.001). In contrast to the TR group, there were no cases of urosepsis or admissions to intensive care in the TP group. The total cancer detection rate by TP biopsy was 70% and the overall pathology detection rate was 88.4%. There was no difference in cancer or pathology detection between operators. A stable level of cancer detection was reached early on for both Prostate Imaging-Reporting and Data System 4 and 5 lesions. All cases performed were performed successfully without need for early termination. CONCLUSION: Implementing a complete transition from TR to TP biopsy can result in a significant reduction in complications and hospital re-admissions. A cognitive freehand coaxial technique is well tolerated by patients and achieves a high cancer detection rate.

A phase I prospective, non-randomized trial of autologous dendritic cell-based cryoimmunotherapy in patients with metastatic castration-resistant prostate cancer.

Metastatic castration-resistant prostate cancer (mCRPC) is an immunologically cold disease with dismal outcomes. Cryoablation destroys cancer tissue, releases tumor-associated antigens and creates a pro-inflammatory microenvironment, while dendritic cells (DCs) activate immune responses through processing of antigens. Immunotherapy combinations could enhance the anti-tumor efficacy. This open-label, single-arm, single-center phase I trial determined the safety and tolerability of combining cryoablation and autologous immature DC, without and with checkpoint inhibitors. Immune responses and clinical outcomes were evaluated. Patients with mCRPC, confirmed metastases and intact prostate gland were included. The first participants underwent prostate cryoablation with intratumoral injection of autologous DCs in a 3 + 3 design. In the second part, patients received cryoablation, the highest acceptable DC dose, and checkpoint inhibition with either ipilimumab or pembrolizumab. Sequentially collected information on adverse events, quality of life, blood values and images were analyzed by standard descriptive statistics. Neither dose-limiting toxicities nor adverse events > grade 3 were observed in the 18 participants. Results indicate antitumor activity through altered T cell receptor repertoires, and 33% durable (> 46 weeks) clinical benefit with median 40.7 months overall survival. Post-treatment pain and fatigue were associated with circulating tumor cell (CTC) presence at inclusion, while CTC responses correlated with clinical outcomes. This trial demonstrates that cryoimmunotherapy in mCRPC is safe and well tolerated, also for the highest DC dose (2.0 × 108) combined with checkpoint inhibitors. Further studies focusing on the biologic indications of antitumor activity and immune system activation could be considered through a phase II trial focusing on treatment responses and immunologic biomarkers.

Magnetic resonance radiomics for prediction of extraprostatic extension in non-favorable intermediate- and high-risk prostate cancer patients.

BACKGROUND: To investigate whether magnetic resonance (MR) radiomic features combined with machine learning may aid in predicting extraprostatic extension (EPE) in high- and non-favorable intermediate-risk patients with prostate cancer. PURPOSE: To investigate the diagnostic performance of radiomics to detect EPE. MATERIAL AND METHODS: MR radiomic features were extracted from 228 patients, of whom 86 were diagnosed with EPE, using prostate and lesion segmentations. Prediction models were built using Random Forest. Further, EPE was also predicted using a clinical nomogram and routine radiological interpretation and diagnostic performance was assessed for individual and combined models. RESULTS: The MR radiomic model with features extracted from the manually delineated lesions performed best among the radiomic models with an area under the curve (AUC) of 0.74. Radiology interpretation yielded an AUC of 0.75 and the clinical nomogram (MSKCC) an AUC of 0.67. A combination of the three prediction models gave the highest AUC of 0.79. CONCLUSION: Radiomic analysis combined with radiology interpretation aid the MSKCC nomogram in predicting EPE in high- and non-favorable intermediate-risk patients.

Impact of positive surgical margins on secondary treatment, palliative radiotherapy and prostate cancer-specific mortality. A population-based study of 13 198 patients.

BACKGROUND: The results of studies evaluating the impact of positive surgical margins on prostate cancer-specific mortality have been inconsistent. We, therefore, evaluated the impact of surgical margin status on subsequent secondary treatment, palliative radiotherapy, and prostate cancer-specific mortality. METHODS: A total of 14 837 men treated with radical prostatectomy (RP) during the period 2001 to 2015 were identified from the Cancer Registry of Norway. Of those, 13 198 (89%) patients had complete data on the preoperative prostate-specific antigen level, pathological T-category, Gleason score in the prostatectomy specimen, and margin status. Multivariable Cox proportional hazards models were used to evaluate the risk, and flexible parametric models for the cumulative incidence were fitted to predict the probabilities of secondary treatment (salvage radiotherapy or prophylactic breast radiation), palliative radiotherapy, and prostate cancer-specific mortality. RESULTS: After a median follow-up time of 5.2 years (3591 patients with ≥8 years of follow-up), positive surgical margins (PSMs) were independently predictive of secondary treatment (hazard ratio [HR] = 2.43, 95% confidence interval [CI] = 2.21-2.66) and palliative radiotherapy (HR = 1.45, 95% CI = 1.03-2.05). After 10 years, the absolute increased risk for palliative radiotherapy in patients with PSMs after RP varied between 0.1% in pT2 tumors with a Gleason score of 6, to 12% for pT3b tumors with a Gleason score of 9 to 10. PSMs were not independently associated with prostate cancer-specific mortality (HR = 1.14, 95% CI = 0.82-1.59). CONCLUSION: PSMs were associated with increased application of secondary treatment and palliative radiotherapy but were not predictive of prostate cancer-specific mortality. As the use of palliative radiotherapy was only marginally increased in patients with PSMs and the lowest-risk disease characteristics, avoiding PSMs may be of greatest prognostic relevance in patients with higher-risk disease characteristics.

The Prognostic Value of Human Papillomavirus Status in Penile Cancer: Outcomes From a Norwegian Cohort Study.

INTRODUCTION: Penile squamous cell carcinoma (PSCC) can develop from human papillomavirus (HPV) infection. This study investigates if the prognostic value of the TNM stage groups or the components tumor stage (pT), grade of differentiation (Grade), lymphovascular invasion (LVI), and nodular stage (pN) depend on HPV status. Also, whether the value of tumor parameters (pT, Grade, and LVI) for predicting node-positive disease depends on HPV status was investigated. PATIENTS AND METHODS: Stored tumor tissue from 226 patients treated for PSCC in Western Norway between 1973 and 2023 was investigated for HPV DNA. Histopathological variables were reevaluated according to the current TNM classification. Disease course was registered from hospital records. Inclusion of an interaction term between HPV and TNM stage groups in Cox regression enabled analysis of whether cancer-specific survival (CSS) of the stage groups depended on HPV status. This was also done separately for pT, Grade, LVI, and pN. Logistic regression with interaction terms between HPV and the tumor parameters were used to investigate if their predictive value depended on HPV status. RESULTS: HPV DNA was detected in 43% of the tumors. Stratified by HPV status, there was no significant interaction term in the Cox regression between HPV status and TNM stage groups (P = .74). Similar results were found for pT (P = .94), Grade (P = .08), LVI (P = .91) and pN (P = .77). Moreover, there were no significant interaction terms in the logistic regression between HPV status and the tumor parameters pT, Grade, and LVI (all P > .2). CONCLUSIONS: This study found that prognosis of the TNM stage groups and the components pT, Grade, LVI, and pN were not modified by HPV in PSCC. The value of pT, Grade, and LVI for predicting lymph node-positive disease was not affected by HPV status.

Salvage Reirradiation for Locally Recurrent Prostate Cancer: Results From a Prospective Study With 7.2 Years of Follow-Up.

PURPOSE: There are no well-established re-treatment options for local recurrence after primary curative radiation therapy for prostate cancer (PCa), as prospective studies with long-term follow-up are lacking. Here, we present results from a prospective study on focal salvage reirradiation with external-beam radiation therapy with a median follow-up of 7.2 years. MATERIALS AND METHODS: From 2013 to 2017, 38 patients with biopsy-proven locally recurrent PCa >2 years after previous treatment and absence of grade 2-3 toxicity from the first course of radiation were included. The treatment was 35 Gy in five fractions to the MRI-based target volume and 6 months of androgen-deprivation therapy starting 3 months before radiation. The Phoenix criteria defined biochemical recurrence-free survival (bRFS), and toxicity was scored according to Radiation Therapy Oncology Group criteria. RESULTS: Median age was 70 years, and median time from primary radiation to prostate-specific antigen (PSA) recurrence was 83 months. The actuarial 2-year and 5-year bRFS were 81% (95% CI, 69 to 94) and 58% (95% CI, 49 to 74), respectively. The actuarial 5-year local recurrence-free survival was 93% (95% CI, 82 to 100), metastasis-free survival was 82% (95% CI, 69 to 95), and overall survival was 87% (95% CI, 76 to 98). Two patients (5%) had durable grade 3 genitourinary toxicity, one combined with GI grade 3 toxicity. A PSA doubling time ≤6 months at salvage, a Gleason score >7, and a PSA nadir ≥0.1 ng/mL predicted a worse outcome. CONCLUSION: Reirradiation with EBRT for locally recurrent PCa after primary curative radiation therapy is clinically feasible and demonstrated a favorable outcome with acceptable toxicity in this prospective study with long-term follow-up.

Refractory Bladder Neck Contracture (BNC) After Radical Prostatectomy: Prevalence, Impact and Management Challenges.

Bladder neck contracture is a recognised complication associated with radical prostatectomy. The management can be challenging, especially when refractory to initial intervention strategies. For the patient, the burden of disease is high and continence status cannot be overlooked. This review serves to provide an overview of the management of this recognised clinical pathology. Consideration needs to be given to minimally invasive approaches such as endoscopic incision, injectables, implantable devices as well as major reconstructive surgery where the condition persists. For the latter, this can involve open and robotic surgery as well as use of grafts and artificial sphincter surgery. These elements underline the need for a tailored and a patient centred approach.

Complications and device failures associated with urolift: Findings from the MAUDE database.

INTRODUCTION: Urolift is an established intervention for symptoms of bladder outflow obstruction caused by benign prostate enlargement. Reported advantages include its minimally invasive profile, short learning curve and feasibility as a day case procedure. Our aim was to use a national registry as a means to evaluate the nature of complications and device failures that have been documented to occur. METHODS: Retrospective review was performed of the US Manufacturer and User Facility Device Experience (MAUDE) database, a prospective register, which contains voluntarily submitted adverse events associated with surgical devices. Information collected include event timing, underlying cause, procedural completion, complications and mortality status. RESULTS: Between 2016 and 2023, 103 device failures, 5 intra-operative complications and 165 post-operative complications (early: 151, late: 14) were registered. The commonest device problem (56%, n = 58) was failure of the implant to deploy with subsequent requirement for complete replacement. There were 50 cases of documented urosepsis. 62 patients with post operative haematuria were registered including 12 that underwent emergency embolisation. Other complications included stroke (n = 5), pulmonary embolism (n = 3) and necrotising fasciitis (n = 1). Twelve ITU admissions were registered. In the reports, 22 cases were filed that recorded a hospital stay of 7 days or more. Eleven deaths were captured in the database over the study period. CONCLUSION: While urolift is recognised as less invasive intervention compared to alternatives such as transurethral resection of the prostate, serious adverse events have been reported to occur including death. Our findings can provide learning points for surgeons and allow for improved patient counselling and treatment planning accordingly.

Penile Cancers Attributed to Human Papillomavirus Are Associated with Improved Survival for Node-positive Patients. Findings from a Norwegian Cohort Study Spanning 50 Years.

BACKGROUND: Human papillomavirus (HPV) infection is a risk factor for the development of penile squamous cell carcinoma (PSCC). It remains inconclusive whether HPV-related PSCC has a different prognosis from non-HPV-related PSCC. OBJECTIVE: To investigate the relationship between HPV status and survival as well as temporal changes in the proportion of HPV-related PSCC. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort of 277 patients treated in Norway between 1973 and 2022 was investigated for HPV DNA in tumor tissue. Clinicopathological variables and disease course were registered. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Kaplan-Meier curves and Cox regression were used to investigate the determinants of cancer-specific survival (CSS). The chi-square test for trend in proportions enabled investigation of temporal changes in the HPV-related proportion of PSCC patients treated in Western Norway (n = 211). RESULTS AND LIMITATIONS: HPV DNA was detected in tumor tissue from 131 (47%) patients. Stratified by HPV status, 5-yr CSS did not differ between groups (p = 0.37). When investigating only node-positive patients, however, presence of HPV DNA was an independent predictor of better survival in multivariable Cox regression after adjustment for age, nodal stage, and adjuvant therapy (hazard ratio 0.54, 95% confidence interval: [0.30-0.99], p = 0.04). In cases from Western Norway, an increasing proportion of HPV-related cases over time was found (p = 0.01). The main limitation is the retrospective study design. CONCLUSIONS: HPV DNA in tumor tissue was associated with significantly better CSS for node-positive patients. The proportion of HPV DNA-positive PSCC has increased significantly in Western Norway over the past 50 yr. PATIENT SUMMARY: We investigated the impact of human papillomavirus (HPV) on the survival of penile cancer patients treated over a 50-yr period in Norway. We found that for patients with lymph node metastasis, survival was better for HPV-related cases. We also found that the proportion of cases due to HPV has increased in Western Norway.

Enhancing PSMA-PET/CT with intravenous contrast: Improved tracer clearance in the prostate bed.

AIMS: We observed hitherto unreported layering of radioactivity in the bladder on PET/CT in prostate cancer (PC) when combined with contrast-enhanced CT (CECT). This effect facilitates assessment of the prostate bed in PC. METHODS: Among 128 patients imaged with [18F]PSMA-1007, we selected all 8 studies without and 28 studies with CECT. 20 patients also underwent PET/MR. As controls, we chose 20 and 16 males studied with [18F]FDG for extrapelvic disease with and without CECT. Posterior anterior (PA) ratio was calculated as SUVpost/SUVant * 100 % based on maximal standard uptake values (SUV) in 20 mm spheres in the anterior and posterior bladder. Four nuclear physicians scored assessibility of the bladder base on a 3-point Likert scale (3 = optimal, 1 = poor). We acquired serial PET/CT over 4 hours of a flask with layering of 100 ml intravenous contrast agent and 100 ml physiological saline with 40 MBq of [18F]PSMA-1007, while a control flask was shaken at the start of the experiment. RESULTS: Layering of tracer was observed in all PET/CT studies with CE-CT, but not in studies without contrast. Median PA ratios were 44 % (interquartile range 33-62) for [18F]PSMA-1007 and 73 % (52-67) for [18F]FDG, respectively. Intravenous contrast improved assessibility scores in PET of the bladder base, but the effect only reached significance in the PET/MR data. In the in vitro data, radioactivity was retained in the aqueous supernatant over the entire experiment whereas there was no separation of phases in the control flask over time. CONCLUSION: When performing PET combined with CECT, sedimentation of contrast agent in the bladder leads to upward displacement of radioactivity, enhancing clarity of PET images in the posterior bladder and the prostate bed on both PET/CT and PET/MR.

Assessing Extraprostatic Extension with Multiparametric MRI of the Prostate: Mehralivand Extraprostatic Extension Grade or Extraprostatic Extension Likert Scale?

Purpose: To validate the MRI grading system proposed by Mehralivand et al in 2019 (the "extraprostatic extension [EPE] grade") in an independent cohort and to compare the Mehralivand EPE grading system with EPE interpretation on the basis of a five-point Likert score ("EPE Likert"). Materials and Methods: A total of 310 consecutive patients underwent multiparametric MRI according to a standardized institutional protocol before radical prostatectomy was performed by using the same 1.5-T MRI unit at a single institution between 2010 and 2012. Two radiologists blinded to clinical information assessed EPE according to standardized criteria. On the basis of the readings performed until 2017, the diagnostic performance of EPE Likert and Mehralivand EPE score were compared using receiver operating characteristics (ROC) and decision curve methodology against histologic EPE as standard of reference. Prediction of biochemical recurrence-free survival (BRFS) was assessed by Kaplan-Meier analysis and log rank test. Results: Of the 310 patients, 80 patients (26%) had EPE, including 33 with radial distance 1.1 mm or greater. Interrater reliability was fair (weighted κ 0.47 and 0.45) for both EPE grade and EPE Likert. Sensitivity for identifying EPE using EPE grade versus EPE Likert was 0.83 versus 0.86 and 0.86 versus 0.91 for radiologist 1 and 2, respectively. Specificity was 0.48 versus 0.58 and 0.39 versus 0.70 (P < .05 for radiologist 2). There were no significant differences in the ROC area under the curve or on decision curve analysis. Both EPE grade and EPE Likert were significant predictors of BRFS. Conclusion: Mehralivand EPE grade and EPE Likert have equivalent diagnostic performance for predicting EPE and BRFS with a similar degree of observer dependence.© RSNA, 2020Keywords: MR-Imaging, Neoplasms-Primary, Observer Performance, Outcomes Analysis, Prostate, StagingSupplemental material is available for this article.See also the commentary by Choyke in this issue.