Primary Whole-gland Ablation for the Treatment of Clinically Localized Prostate Cancer: A Focal Therapy Society Best Practice Statement.

CONTEXT: Whole-gland ablation is a feasible and effective minimally invasive treatment for localized prostate cancer (PCa). Previous systematic reviews supported evidence for favorable functional outcomes, but oncological outcomes were inconclusive owing to limited follow-up. OBJECTIVE: To evaluate the real-world data on the mid- to long-term oncological and functional outcomes of whole-gland cryoablation and high-intensity focused ultrasound (HIFU) in patients with clinically localized PCa, and to provide expert recommendations and commentary on these findings. EVIDENCE ACQUISITION: We performed a systematic review of PubMed, Embase, and Cochrane Library publications through February 2022 according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. As endpoints, baseline clinical characteristics, and oncological and functional outcomes were assessed. To estimate the pooled prevalence of oncological, functional, and toxicity outcomes, and to quantify and explain the heterogeneity, random-effect meta-analyses and meta-regression analyses were performed. EVIDENCE SYNTHESIS: Twenty-nine studies were identified, including 14 on cryoablation and 15 on HIFU with a median follow-up of 72 mo. Most of the studies were retrospective (n = 23), with IDEAL (idea, development, exploration, assessment, and long-term study) stage 2b (n = 20) being most common. Biochemical recurrence-free survival, cancer-specific survival, overall survival, recurrence-free survival, and metastasis-free survival rates at 10 yr were 58%, 96%, 63%, 71-79%, and 84%, respectively. Erectile function was preserved in 37% of cases, and overall pad-free continence was achieved in 96% of cases, with a 1-yr rate of 97.4-98.8%. The rates of stricture, urinary retention, urinary tract infection, rectourethral fistula, and sepsis were observed to be 11%, 9.5%, 8%, 0.7%, and 0.8%, respectively. CONCLUSIONS: The mid- to long-term real-world data, and the safety profiles of cryoablation and HIFU are sound to support and be offered as primary treatment for appropriate patients with localized PCa. When compared with other existing treatment modalities for PCa, these ablative therapies provide nearly equivalent intermediate- to long-term oncological and toxicity outcomes, as well as excellent pad-free continence rates in the primary setting. This real-world clinical evidence provides long-term oncological and functional outcomes that enhance shared decision-making when balancing risks and expected outcomes that reflect patient preferences and values. PATIENT SUMMARY: Cryoablation and high-intensity focused ultrasound are minimally invasive treatments available to selectively treat localized prostate cancer, considering their nearly comparable intermediate- to long term cancer control and preservation of urinary continence to other radical treatments in the primary setting. However, a well-informed decision should be made based on one's values and preferences.

Axumin (18F-Fluciclovine) PET imaging in men exhibiting no clinically significant cancer on initial negative biopsy of PI-RADS 4 and 5 regions of interest.

PURPOSE: The objective of the study was to determine whether Axumin (18F-Fluciclovine) PET/MRI informs the decision to perform an early repeat biopsy of PI-RADS 4/5 region of interest (ROI) exhibiting no clinically significant prostate cancer (csPCa) on initial biopsy. METHODS: This prospective study enrolled men with at least one PI-RADS 4/5 ROI on multi-parametric MRI and no csPCa on prior biopsy defined as Gleason grade group (GGG) > 1. All men underwent an Axumin PET/MRI and only-persistent PI-RADS > 2 ROI were advised to undergo a repeat biopsy. A PET cancer suspicion score (PETCSS) was internally developed to stratify PET avid lesions according to their suspicion of harboring csPCa. The sensitivity, specificity, positive (PPV) and negative predictive value (NPV) of the PETCSS for predicting csPCa were assessed. Relative risk was calculated to analyze the association of baseline variables with csPCa on repeat biopsy. RESULTS: Thirty-eight ROI on 36 enrolled men were analyzed. Fourteen (36.8%) were downgraded to PI-RADS 1/2 and were not subjected to repeat biopsy. Thirteen (92.9%) of these downgraded scans also exhibited low-risk PETCSS. Overall, 18/22 (81.2%) subjects underwent a repeat per protocol biopsy. Of the 20 ROI subjected to repeat biopsy, eight (40%) were found to harbour csPCa. The sensitivity, specificity, PPV and NPV of the PETCSS were 50, 50, 40, and 60%, respectively. No predictor of csPCa was found in the risk analysis. CONCLUSION: Our pilot study showed that both MRI and PET sequences have limited performance for identifying those persistently suspicious PI-RADS 4/5 ROI that are found to harbor csPCa on repeat biopsy.

A prospective study of cancer detection rates following early repeat imaging and biopsy of PI-RADS 4 and 5 regions of interest exhibiting no clinically significant prostate cancer on prior biopsy.

INTRODUCTION: We aimed to determine cancer detection rates following early repeat multiparametric magnetic resonance imaging (mpMRI) and biopsy of Prostate Imaging-Reporting and Data System (PI-RADS), v2.1 4 and 5 regions of interest (ROI) exhibiting no clinically significant prostate cancer (csPCa) on prior biopsy and to identify predictors for these missed csPCa. METHODS: Between January 2019 and August 2020, 36 men with 38 PI-RADS 4 or 5 ROI with no evidence of csPCa (defined as Gleason grade group [GGG] >1) on prior MRI fusion target biopsy (MRFTB) + systematic biopsy (SB) were invited to participate in the present prospective study. All men underwent repeat mpMRI and persistent PI-RADS >2 ROI were advised to undergo repeat MRFTB + SB. Cancer detection rates of any and csPCa were determined. Relative risk was calculated to analyze association of baseline variables with the finding of csPCa on repeat biopsy. RESULTS: Of the 38 initial PI-RADS 4 and 5 ROI, on followup mpMRI, 14 were downgraded to PI-RADS 1/2 and, per protocol, did not undergo repeat biopsy and; eight (33%), 12 (50%), and four (17%) were PI-RADS 3, 4, and 5, respectively. Of these 24 persistently suspicious mpMRI ROI, 20 (83%) underwent repeat biopsy and six (30%), six (30%), and eight (40%) were benign, GGG 1, and GGG >1, respectively. Only prostate-specific antigen ≥10 ng/mL was a predictor for missed csPCa. CONCLUSIONS: Our prospective study supports a recommendation for early repeat mpMRI of all PI-RADS 4 or 5 ROI exhibiting no csPCa, with repeat MRFTB + SB of persistent PI-RADS >2 ROI.

MRI predicts prostatic urethral involvement in men undergoing radical prostatectomy: implications for cryo-ablation of localized prostate cancer.

PURPOSE: To determine whether multi-parametric magnetic resonance imaging (mpMRI) can reliably predict proximity of prostate cancer to the prostatic urethra in a contemporary series of men undergoing radical prostatectomy (RP) at two academic centers. METHODS: Clinical characteristics of consecutive men undergoing pre-operative mpMRI prior to RP and whole-mount axial serial step-sectioned pathology examination at two academic centers between Jun 2016 and Oct 2018 were analyzed retrospectively. Every tumor was characterized by its pathologic minimum distance to the prostatic urethral lumen (pMDUL). Only the cancer closest to the urethra represented the prostatic urethral index lesion. The radiologic minimum distance of the index lesion to the prostatic urethral lumen was measured and noted as ≤ 5 mm versus > 5 mm. The sensitivity, specificity, positive and negative predicting values (PPV and NPV) and area under the receivers operating characteristics curve (AUC) were calculated for performance of mpMRI for predicting pMDUL ≤ 5 mm. RESULTS: Of the 163 surgical specimens examined, 112 (69%) exhibited a pMDUL ≤ 5 mm. These men had significantly higher grade group (GG) and advanced pathological and clinical stage. The rates of high PI-RADS score and presence of gross extracapsular extension were also significantly greater for the group with pMDUL ≤ 5 mm. The AUC, sensitivity, specificity, PPV, and NPV were 0.641, 51.8, 76.5, 82.9, and 42.4%, respectively, for mpMRI to predict pMDUL < 5 mm. CONCLUSIONS: Nearly 70% of men undergoing RP present with tumor within 5 mm of the prostatic urethra. These tumors present higher risk characteristics, and mpMRI exhibited moderate performance and high PPV in their pre-operative detection. Physicians performing partial gland ablation should take these results into consideration during treatment selection and planning.

Early oncological control following partial gland cryo-ablation: a prospective experience specifying reflex MRI guided biopsy of the ablation zone.

BACKGROUND: Several consensus statements recommend serial serum prostate-specific antigen (PSA), multi parametric magnetic resonance imaging (mpMRI), and prostate biopsy following partial gland ablation. We determined the rate of persistent in-field disease following primary partial gland cryo-ablation and whether PSA or mpMRI are reliable predictors of in-field disease persistence. METHODS: Between March 2017 and July 2019, subjects meeting eligibility criteria for partial gland cryoablation were enrolled into an IRB approved outcomes registry. PSA, mpMRI, and prostate biopsy (four cores targeting the ablation zone + six ipsilateral systematic cores) were performed per protocol 6 months following intervention. Binary logistic regression was employed to calculate odds ratio (OR) of PSA decrease, and suspicious mpMRI effect on cancer persistence. The performance of mpMRI for predicting in-field persistence of PCa was evaluated by area under the receiver operation characteristics curve (AUC). RESULTS: Of the 83 eligible men undergoing partial gland cryoablation, 70 (84.3%) underwent 6-month protocol prostate biopsy. Five (7.1%) biopsies exhibited any in-field disease persistence. Only one (1.4%) of these cancers was Gleason grade > 1. Neither PSA decrease or suspicious mpMRI reliably predicted cancer persistence, with OR of 1.6 (0.25-8.6) and 1.5 (0.02-1.3), respectively. AUC of mpMRI for predicting in-field disease persistence was 0.554. CONCLUSIONS: In this cohort of patients undergoing partial gland cryo-ablation, the incidence of persistent disease was low. PSA and mpMRI were not reliable predictors of in-field disease persistence. Based on these data, consideration may be given to deferring early follow-up biopsy in appropriate patients.

Primary Robot-assisted Retroperitoneal Lymph Node Dissection for Men with Nonseminomatous Germ Cell Tumor: Experience from a Multi-institutional Cohort.

BACKGROUND: Primary robot-assisted retroperitoneal lymph node dissection (RA-RPLND) for men with nonseminomatous germ cell tumor (NSGCT) is an alternative to open RPLND for stage I and select stage II patients. OBJECTIVE: To report the complication rates and oncologic outcomes from a multi-institutional series, and to estimate reduction in chemotherapy by using upfront minimally invasive surgery. DESIGN, SETTING, AND PARTICIPANTS: A retrospective chart review of men undergoing primary robot-assisted RPLND between 2014 and 2019 in five institutions by eight urologists experienced in testis cancer and robotic surgery. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Variables such as demographic and clinicopathologic information, operative parameters and complication rates, oncologic outcomes, sexual recovery, and hospital length of stay were collected. Descriptive statistics are presented. RESULTS AND LIMITATIONS: Forty-nine patients were analyzed with a median follow-up of 15.0 mo (interquartile range 6.5-29.1 mo). Median operative time was 288 min, estimated blood loss was 100 ml, and lymph node yield was 32. Median length of stay was 1 d. There were nine postoperative complications, 44% (4/9) of which were Clavien grade 1. There were no Clavien grade IV complications. Twenty-one patients had metastatic NSGCT (42.8%), of whom nine (18.4%) received adjuvant chemotherapy. Four patients experienced recurrence (three out-of-field and one in-field recurrence). Limitations include the retrospective study design and various surgical techniques among surgeons. CONCLUSIONS: Primary robot-assisted RPLND for NSGCT can be performed safely, with low complication rates and acceptable oncologic outcomes reducing the need for chemotherapy. For a population in which compliance with surveillance is typically challenging, robot-assisted RPLND may improve quality of care and outcomes for patients with NSGCT. PATIENT SUMMARY: In experienced centers, robot-assisted retroperitoneal lymph node dissection can be performed safely with similar oncologic outcomes to an open approach, while providing an option that may reduce the need for chemotherapy.

Minimally Invasive Surgery for Patients with Locally Advanced and/or Metastatic Renal Cell Carcinoma.

Despite advances in systemic therapy and immunotherapy, surgery continues to have a role in management of advanced renal cell carcinoma (aRCC). Minimally invasive surgery (MIS) is considered standard of care for smaller, localized tumors due to faster recovery without compromising oncologic outcomes. There are concerns about MIS for aRCC due to a potential risk of inferior oncologic outcomes and unusual patterns of disease recurrence. Recent studies, however, suggest that in properly selected patients with aRCC, MIS can provide improved peri-operative outcomes without compromising oncologic control.

Oncological control following partial gland ablation for intermediate-risk prostate cancer.

Historically, the primary objection to partial gland ablation (PGA) for management of prostate cancer (CaP) has been disease multifocality and inability to localize significant disease. Improved disease localization and risk stratification with multiparametric magnetic resonance imaging and targeted biopsy, along with its minimal adverse impact on quality of life has enabled PGA to gain acceptance. Today, the primary barrier for adopting PGA is its unknown oncological outcomes. Objectives of this review are to provide a rationale for PGA for managing intermediate-risk (IR) CaP; review oncological outcomes following PGA for IR disease; and assess whether there is adequate data to justify PGA for management of IR CaP. There is no consensus how to assess or define oncological outcomes following PGA. We propose the following definitions for oncological outcomes: Oncological control (detection of any cancer following biopsy), oncological failure (detection of Gleason grade group >1 on follow-up biopsy), and oncological treatment failure (any disease that precipitate salvage treatment). There are only 3 reports in the literature where inclusion criteria specified pretreatment targeted biopsy and reflex prostate biopsy within 1 year of PGA in cohorts of men where >50% had Gleason grade group >1 disease. These studies reported that prostate-specific antigen is not a reliable surrogate and multiparametric magnetic resonance imaging is reliable when prevalence of in-field CaP is high. "Freedom from failure" is used to assess longer-term oncologic outcomes, and is defined by freedom from CaP mortality, androgen deprivation therapy, or whole-gland treatment. Rationale for PGA in selected cases of IR CaP is compelling and early oncological studies are reassuring. If patient selection is done judiciously, oncologic outcomes are disclosed, and follow-up plan is rigorously implemented, it is unlikely rates of metastasis or CaP mortality with be adversely impacted and many men will avoid or defer adverse effects of whole-gland treatment.

Concordance and Performance of 4Kscore and SelectMDx for Informing Decision to Perform Prostate Biopsy and Detection of Prostate Cancer.

OBJECTIVES: To compare both the concordance between the 4Kscore and SelectMDx for informing decision to perform prostate biopsy (PB) and the performance of these tests for detecting clinically significant prostate cancer (csPCa). Several biomarkers were developed to inform decisions whether to perform a PB based on the probability of detecting csPCa. There is a paucity of studies directly comparing them METHODS: Between 11/2018 and 4/2019, all new referrals with the diagnosis of elevated PSA were advised to undergo 4Kscore and SelectMDx in order to guide the selection of candidates for PB. Men were advised to undergo PB if the reported biomarker risk for detecting csPCA was ≥7.5%, or if they presented a Prostate Image Reporting and Data System ≥1 MRI. Cohen's Kappa was used to assess the concordance between the binary 4Kscore and SelectMDx results using externally validated cutoffs of 7.5% and 12%. Receiver operating characteristics curve and area under the curve (AUC) assessed the performance of each biomarker for distinguishing csPCa. RESULTS: Of 128 consecutive patients referred, 114 (89.1%) underwent 4Kscore and SelectMDx. The kappa coefficient between the biomarkers using the 7.5% cutoff was 0.184 (poor concordance) and 0.22 using the 12% cutoff. The two biomarkers yielded discordant guidance whether to proceed with PB in 46% and 38% of cases, respectively. csPCa was found in 22 of the 50 patients who underwent PB (44%). The AUC for 4Kscore and SelectMDx was 0.830 (95% confidence interval [CI]: 0.710 - 0.949) and 0.672 (95%CI: 0.517 - 0.828; P = .036) for csPCa, respectively. CONCLUSION: The discordance observed between the 4Kscore and SelectMDx is disconcerting. The 4Kscore when combined with magnetic resonance imaging was superior to the SelectMDx for detecting csPCa. Prospective comparative studies must be performed to optimize implementation of biomarkers for selecting candidates for PB.

Dorsal oral mucosa graft in combination with ventral penile flap as an alternative to repair obliterative stenosis of the anterior urethra in a single surgical time

ABSTRACT Purpose: Obliterative urethral stenosis is a type of urethral lesion that compromises the whole corpus spongiosum's circumference. We present our experience in resolving complex long segment urethral obliteration in a single procedure using a combination of dorsal onlay oral mucosa graft (OMG) and ventral fasciocutaneous penile skin flap. Materials and methods: A prospectively maintained database was reviewed, which included data of men presenting long, obliterative strictures. Patients were excluded if they were lost to follow-up before one year. Failure was defined as need for further urethral instrumentation. The surgical technique used consisted on the fixation of OMG to the tunica albuginea of the corpus cavernosum, thus creating a new urethral plate. Penile or foreskin flaps were employed to complete the ventral aspect. Postoperative follow-up was done with a voiding cystourethrography at week 3. Results: A total of 21 patients were included with a median age of 49 years. Mean follow-up was 25 months. Failure was found for 3 patients (2 of them needing dilations and only one required a new urethral reconstruction). Conclusion: Single stage combination of dorsal OMG with ventral fasciocutaneous penile flap showed good results for selected patients affected with obliterative urethral stenosis.

Dorsal oral mucosa graft in combination with ventral penile flap as an alternative to repair obliterative stenosis of the anterior urethra in a single surgical time.

PURPOSE: Obliterative urethral stenosis is a type of urethral lesion that compromises the whole corpus spongiosum's circumference. We present our experience in resolving complex long segment urethral obliteration in a single procedure using a combination of dorsal onlay oral mucosa graft (OMG) and ventral fasciocutaneous penile skin flap. MATERIALS AND METHODS: A prospectively maintained database was reviewed, which included data of men presenting long, obliterative strictures. Patients were excluded if they were lost to follow-up before one year. Failure was defined as need for further urethral instrumentation. The surgical technique used consisted on the fixation of OMG to the tunica albuginea of the corpus cavernosum, thus creating a new urethral plate. Penile or foreskin flaps were employed to complete the ventral aspect. Postoperative follow-up was done with a voiding cystourethrography at week 3. RESULTS: A total of 21 patients were included with a median age of 49 years. Mean follow-up was 25 months. Failure was found for 3 patients (2 of them needing dilations and only one required a new urethral reconstruction). CONCLUSION: Single stage combination of dorsal OMG with ventral fasciocutaneous penile flap showed good results for selected patients affected with obliterative urethral stenosis.

Update on the guideline of guidelines: non-muscle-invasive bladder cancer.

Non-muscle-invasive bladder cancer (NMIBC) is the most common form of bladder cancer, with frequent recurrences and risk of progression. Risk-stratified treatment and surveillance protocols are often used to guide management. In 2017, BJUI reviewed guidelines on NMIBC from four major organizations: the American Urological Association/Society of Urological Oncology, the European Association of Urology, the National Comprehensive Cancer Network, and the National Institute for Health and Care Excellence. The present update will review major changes in the guidelines and broadly summarize new recommendations for treatment of NMIBC in an era of bacillus Calmette-Guérin shortage and immense novel therapy development.

Prostate Cancer Screening and Management in Solid Organ Transplant Candidates and Recipients.

The number of solid organ transplantations is increasing worldwide. Major medical advances have allowed for incremented survival in this population, which, because approximately 50% of recipients are over age 50 years, makes for an increasingly older population of transplant survivors. This article discusses controversies and current guidelines related to prostate cancer (PCa) screening, detection, and treatment for men in the general population. The relevant literature is reviewed in order to provide insights on how to optimize PCa screening, detection, and treatment pre- and post-solid organ transplantation. There is compelling evidence that immunosuppression does not increase the risk for the development or progression of PCa following solid organ transplantation. Therefore, PCa screening, detection, or treatment should not be influenced by the impact of immunosuppression on the biology of the disease. Prostate-specific antigen (PSA) appears to be as reliable for PCa screening of transplant candidates and recipients as it is for the general population. There is no consensus on how or when it should be implemented. Evidence is also equivocal as to the suggested waiting time between treatment and transplantation. Surgery and radiation therapy appear to be safe and provide good outcomes for managing PCa in solid organ transplant candidates and recipients. However, certain precautions should be taken with this vulnerable population, especially for kidney transplant patients given the pelvic location of the renal graft. Partial gland ablation of PCa should be considered in appropriate candidates.

Autologous fat as a rectal-prostate spacer for prostate brachytherapy: Results at 6 months.

PURPOSE: Implanted rectal spacers (IRS) have been developed to increase the distance between the prostate and the rectum, thus optimizing dose escalation. Cost is a disadvantage and there are still uncertainties as to their durability. We have developed an autologous fat transfer (AFT) technique to use as an IRS. We aim to present the feasibility and durability at 6 months of AFT placed immediately after the implant of the seeds in low-dose-rate brachytherapy (BT). METHODS AND MATERIALS: Thirty-five patients underwent AFT (12 were treated with primary BT, 7 with a combined primary treatment of external beam radiotherapy + BT, 16 with salvage BT). The isodose used for primary BT was 14400 cGy, 11,000 cGy after 4600 cGy of external beam radiotherapy in the combined group, and 14400 cGy for the salvage group. Patients underwent a CT scan at 1, 3, and 6 months to measure the distance between the rectum and the prostate. RESULTS: An average of 32.7 cc (20-40) of fat was transferred successfully in 100% of cases. The mean distance to the rectum at the level of the base, middle, and apex at 1 and 6 months were 11.2, 9.7, and 7.6 mm; 8.3, 8.1, and 5.9 mm, respectively. No rectal toxicity or major complications were reported. CONCLUSIONS: The use of fat as an IRS seems to be a valid alternative to reduce rectal toxicity after BT, achieving equivalent distances to synthetic IRS. It is feasible, safe, and the loss of distance at 6 months is small. Cost is lower than other alternatives.