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Salvage radical prostatectomy following focal therapy: functional and oncological outcomes

Herrera-Caceres, Jaime O; Nason, Gregory J; Salgado-Sanmamed, Noelia; Goldberg, Hanan; Woon, Dixon T S; Chandrasekar, Thenappen; Ajib, Khaled; Tan, Guan Hee; Alhunaidi, Omar; van der Kwast, Theodorus; Finelli, Antonio; Zlotta, Alexandre R; Hamilton, Robert J; Berlin, Alejandro; Perlis, Nathan; Fleshner, Neil E
OBJECTIVES:To report the oncological and functional outcomes of salvage radical prostatectomy (sRP) after focal therapy (FT). PATIENTS AND METHODS:A retrospective review of all patients who underwent sRP after FT was performed. Clinical and pathological outcomes focussed on surgical complications, oncological, and functional outcomes. RESULTS:In all, 34 patients were identified. The median (interquartile range [IQR]) age was 61 (8.25) years. FT modalities included high-intensity focussed ultrasound (19 patients), laser ablation (13), focal brachytherapy (one) and cryotherapy (one). The median (IQR) time from FT to recurrence was 10.9 (17.6) months. There were no rectal or ureteric injuries. Two (5.9%) patients had iatrogenic cystotomies and four (11.8%) developed bladder neck contractures. The mean (sd) hospital stay was 2.5 (2.1) days. The T-stage was pT2 in 14 (41.2%) patients, pT3a in 16 (47.1%), and pT3b in four (11.8%). In all, 13 (38%) patients had positive surgical margins (PSMs). Six (17.6%) patients received adjuvant radiotherapy (RT). At a mean follow-up of 4.3 years, seven (20.6%) patients developed biochemical recurrence (BCR), and of these, six (17.6%) patients required salvage RT. PSMs were associated with worse BCR-free survival (hazard ratio 6.624, 95% confidence interval 2.243-19.563; P < 0.001). The median (IQR) preoperative International Prostate Symptom Score and International Index of Erectile Function score was 7 (4.5-9.5) and 23.5 (15.75-25) respectively, while in the final follow-up the median (IQR) values were 7 (3.5-11) and 6 (5-12.25), respectively (P = 0.088 and P < 0.001). At last follow-up, 31 (91.2%) patients were continent, two (5.9%) had moderate (>1 pad/day) incontinence, and one (2.9%) required an artificial urinary sphincter. CONCLUSIONS:sRP should be considered as an option for patients who have persistent clinically significant prostate cancer or recurrence after FT. PSMs should be recognised as a risk for recurrent disease after sRP.
PMID: 31863617
ISSN: 1464-410x
CID: 4954062

Photoselective vaporization of the prostate: study outcomes as a function of risk of bias, conflicts of interest, and industrial sponsorship

Wettstein, Marian S; Pazhepurackel, Clinsy; Neumann, Aline S; Woon, Dixon T S; Herrera-Caceres, Jaime O; Kozomara, Marko; Poyet, Cédric; Sulser, Tullio; Kulkarni, Girish S; Hermanns, Thomas
PURPOSE/OBJECTIVE:To investigate the outcomes of comparative studies on photoselective vaporization of the prostate (PVP) as a function of risk of bias (RoB), conflicts of interest (COI), and industrial sponsorship (IS). METHODS:We performed a systematic literature search for comparative studies on PVP [randomized controlled trials (RCTs) and non-randomized comparative studies (NRCSs)]. Study selection as well as comprehensive assessment of RoB, COIs, and IS were performed in duplicate. The identified studies were further rated by two independent board-certified urologists as either PVP-favourable or PVP-unfavourable. Descriptive statistics were performed among all identified studies and among the subgroups of studies rated as favourable and unfavourable, respectively. RESULTS:Sixty-five studies qualified for inclusion (25 RTCs and 40 NRCSs) of which 56 (86%) were rated favourable and 9 (14%) unfavourable. A majority of all studies mentioned the absence/presence of potential COIs (78%). In contrast, a sponsorship statement was only found in 29% of the investigations. Studies rated favourable demonstrated a higher percentage of COIs (39% versus 22%). IS was exclusively found among favourable studies. Furthermore, a serious or critical RoB was more often found in favourably rated NRCSs. CONCLUSIONS:COIs and IS seem to be associated with favourable study outcomes in comparative studies on PVP. The transparency of the whole research process from study conception to the dissemination of the results has to be further improved to prevent a harmful effect of COIs and IS on the internal validity of studies.
PMID: 31087122
ISSN: 1433-8726
CID: 4954022

Questioning the Status Quo: Should Gleason Grade Group 1 Prostate Cancer be Considered a "Negative Core" in Pre-Radical Prostatectomy Risk Nomograms? An International Multicenter Analysis

Leong, Joon Yau; Herrera-Caceres, Jaime O; Goldberg, Hanan; Tham, Elwin; Teplitsky, Seth; Gomella, Leonard G; Trabulsi, Edouard J; Lallas, Costas D; Fleshner, Neil E; Tilki, Derya; Chandrasekar, Thenappan
OBJECTIVE:To assess the impact of excluding Gleason Grade Group 1 (GG1) prostate cancer (CaP) cores from current pre-radical prostatectomy (RP) nomograms. METHODS:Multi-institutional retrospective chart review was performed on all RP patients with prostate biopsy between 2008 and 2018. Patients were individually assessed using the Memorial Sloan Kettering Cancer Center (MSKCC) and Briganti nomograms using the following iterations: (1) Original [ORIG] - all available core data and (2) Selective [SEL] - GG1 cores considered negative. Nomogram outcomes - lymph node invasion (LNI), extracapsular extension (ECE), organ-confined disease (OCD), seminal vesicle invasion (SVI), were compared across iterations and stratified based on biopsy GG. Clinically significant impact on management (CSIM) was defined as change in LNI risk above or below 2% or 5% (Δ2/Δ5). Nomogram outcomes were validated with RP pathology. RESULTS:7718 men met inclusion criteria. In men with GG2 who also had GG1 cores, SEL better predicted LNI (MSKCC - ORIG 4.97% vs SEL 3.50%; Briganti - ORIG 4.81% vs SEL 2.49%, RP outcome 2.46%), OCD (MSKCC - ORIG 40.91% vs SEL 48.44%, RP outcome: 68.46%) and ECE (MSKCC - ORIG 57.87% vs SEL 50.38%, RP outcome: 30.41%), but not SVI (MSKCC - ORIG 5.42% vs SEL 3.34%, RP outcome: 5.62%). This was also consistent in patients with GG3-5 disease. The greatest CSIM was on GG1-2 CaP; Δ2 and Δ5 in GG1 patients was 26.3%-31.0% and 1.5%-5.2%, respectively, and Δ2 and Δ5 in GG2 patients was 3.4%-22.2% and 12.3%-13.6%, respectively. CONCLUSION/CONCLUSIONS:Excluding GG1 CaP cores from pre-RP nomograms better predicts final RP pathologic outcomes. More importantly, this may better reflect extent of true cancer burden.
PMID: 31705947
ISSN: 1527-9995
CID: 4954052

Smarter screening for prostate cancer

Tan, Guan Hee; Nason, Gregory; Ajib, Khaled; Woon, Dixon Teck Sing; Herrera-Caceres, Jaime; Alhunaidi, Omar; Perlis, Nathan
PURPOSE/OBJECTIVE:Prostate cancer is the second commonest cancer among men. In the large European Randomized Study of Screening for Prostate Cancer (ERSPC) trial, prostate-specific antigen (PSA) screening has been shown to substantially reduce prostate cancer mortality. However, PSA screening is known to lead to more unnecessary prostate biopsies and over-diagnosis of clinically insignificant cancer. Therefore, it is imperative that smarter screening methods be developed to overcome the weaknesses of PSA screening. This review explores the novel screening tools that are available. METHODS:A comprehensive literature search was performed using PubMed regarding newer biomarkers, imaging techniques and risk-predicting models that are used to screen for prostate cancer in mainly biopsy-naïve men. RESULTS:and prostate health index (PHI) are generally better than PSA alone in detecting clinically significant cancer. Similarly, urine-based biomarkers like prostate cancer antigen 3 (PCA3) and HOXC6/DLX1 have been shown to be more accurate than PSA screening. More recently, multiparametric magnetic resonance imaging (mpMRI) is gaining popularity for its ability to detect clinically significant cancer. There is also evidence that combining individual tests to develop prediction models can reliably predict high-risk prostate cancers while reducing the number of unnecessary biopsies. Combinations such as the Stockholm-3 model (STHLM3) and other novel combinations are presented in this review. CONCLUSION/CONCLUSIONS:While we continue to find the smarter screening methods that are reliable, precise, and cost-effective, we continue to advocate shared decision-making in prostate cancer screening in order to work in our patients' best interests.
PMID: 30859272
ISSN: 1433-8726
CID: 4954012

The who, when, and why of primary adrenal malignancies: Insights into the epidemiology of a rare clinical entity

Chandrasekar, Thenappan; Goldberg, Hanan; Klaassen, Zachary; Wallis, Christopher J D; Woon, Dixon T S; Herrera-Caceres, Jaime O; Kulkarni, Girish S; Fleshner, Neil E
BACKGROUND:Primary malignancies of the adrenal glands are rare. Epidemiologic assessment of primary adrenal malignancies is lacking and has been limited to case reports and series. Population-level data can provide a better understanding of the incidence, distribution, and prognostic factors associated with these rare malignancies. METHODS:The Surveillance, Epidemiology, and End Results database (1973-2013) was queried for all patients who were diagnosed with primary adrenal malignancies, categorized in 5 histologic groups: adrenocortical carcinoma (ACC), pheochromocytoma and paraganglioma (PH), neuroblastoma (NE), non-Hodgkin lymphoma (NHL), and sarcoma (SA). Age-adjusted incidence, distribution trends, and cancer-specific survival (CSS) for each group were analyzed. RESULTS:In total, 4695 patients with primary adrenal malignancies were identified, including 2057 with ACC, 512 with PH, 1863 with NE, 202 with NHL, and 61 with SA. The age-adjusted incidence of all 5 histologic subtypes was rising. Age at presentation differed substantially by histologic group: NE was the most prevalent during the first decade of life, whereas ACC predominated after age 30 years, and NHL outnumbered PH after age 70 years. Patient-specific factors were not associated with advanced disease at the time of presentation. The 5-year CSS rate for each histologic subtype was 38% for ACC, 69% for PH, 64% for NE, 38% for NHL, and 42% for SA. Survival outcomes for patients with ACC, NHL, PH and SA remained unchanged over the 40-year study period. Multimodal therapy was associated with higher CSS in patients with NE. CONCLUSIONS:This first population-level analysis of all primary adrenal malignancies provides important initial data regarding presentation and clinical outcomes. Notably, except for patients with NE, the survival of patients with these rare cancers has not improved over the past 40 years.
PMID: 30561782
ISSN: 1097-0142
CID: 4953992

Renal tumor biopsy: indicators, technique, safety, accuracy results, and impact on treatment decision management

Herrera-Caceres, Jaime O; Finelli, Antonio; Jewett, Michael A S
CONTEXT/BACKGROUND:Renal tumor biopsy (RTB), as distinct from the more common renal biopsy for medical renal disease, is an option for patients with renal masses. It is mainly used for small renal masses (SRM) but it may also be indicated for larger masses and even in the presence of metastatic disease. Its main indication in SRM is to avoid intervention for benign kidney tumors but increasingly enables more personalized treatment for kidney cancer patients. OBJECTIVE:The objective of this paper is to provide a comprehensive review of the most recent literature available for RTB including the indications, the technique and also the possible complications. RESULTS:The urological community continues to optimize the indications for RTB. Non-operative treatment modalities, such as active surveillance, ablative modalities, and immunotherapy, may have different results influenced by tumor histology. Continuing concern regarding complications and accuracy and, therefore, the utility of RTB has been addressed. Recent reports support the potential benefit of RTB, safely avoiding a significant number of interventions with good results and minimal complications. CONCLUSION/CONCLUSIONS:Urologists should be aware of the benefits of RTB and develop experience with this technique to optimize the results. This diagnostic strategy should be discussed with patients and adopted as it has been with other solid tumors.
PMID: 30022406
ISSN: 1433-8726
CID: 4953972

Future developments in ureteral stents

Wiesinger, Clemens G; Lee, Jason; Herrera-Caceres, Jaime O
PURPOSE OF REVIEW:We present a review of recent literature to summarize the most recent evidence on the use of ureteral stents, including the use of different materials and treatment of stent-related symptoms. RECENT FINDINGS:Metal stents are able to resist lumen occlusion from extrinsic compression allowing longer indwelling time and making them an option for long-term use. Biodegradable stents have the advantage not to require secondary procedures; however, they have not proven their safety in the clinical setting yet. Coated and drug-eluting stents seem to be promising concepts to prevent stent-related symptoms, but still have to be considered as experimental approaches. The most commonly used stent type is the standard double J stent, named for its J-shaped curled ends and manufactured from polyurethane, silicone or various polymers. SUMMARY:After more than 5 decades of using stents there are promising advancements in their designs and materials aiming to maintain their patency and control stent-related symptoms. Long-term metallic stents and coated stents are good options that should be considered in selected patients. Biodegradable stents are promising developments but not sophisticated yet. Pain medication, alpha-blocker and antimuscarinic medications are still frequently used and necessary. Treatment combinations can result in better outcomes than monotherapy.
PMID: 30531433
ISSN: 1473-6586
CID: 4953982

Active surveillance in intermediate risk prostate cancer

Chandrasekar, Thenappan; Herrera-Caceres, Jaime O; Klotz, Laurence
OBJECTIVES:Active Surveillance (AS) has become an established treatment option for men with low-risk prostate cancer (PCa), demonstrating superior functional outcomes and excellent oncologic outcomes.As such, it has been appealing to extend AS to patients with intermediate risk PCa. We provide a review of the current experience with AS in the intermediate-risk PCa population. METHODS:Risk stratification is the key to treatment success. Many clinical factors (age, percent Gleason 4, PSA density, race/ethnicity, and genetic predisposition) and genomic markers have proven prognostic value in the AS population. We performed a systematic review of the currently available data (randomized trials and prospective cohort studies) to establish the status of AS in the intermediate risk patient population. RESULTS:Our ability to predict the natural history of intermediate risk prostate cancer is imperfect. While the benefits of AS make it an appealing option for men with intermediate risk disease, the published experience todate demonstrates that AS for all men with intermediate risk disease leads to higher rates of metastatic disease and loss of the opportunity for cure. These same studiesalso demonstrate that a subset of patients with intermediate risk disease have indolent disease that may benefit from AS. This heterogeneity is not adequately captured with traditional histopathologic staging. Clinical, genomic, and radiologic biomarkers play a key role in appropriate risk stratification and patient selection. The optimal use of these biomarkers in the intermediate riskpatient is currently the subject of intense evaluation. CONCLUSION:Active surveillance for men at the favorable end of intermediate risk prostate cancer is an appealing alternative to radical therapy, but carries a modest but increased risk of metastatic disease compared to low risk cancer. Many biomarkers are currently being evaluated to enhance precise risk stratification of this important subgroup of patients.
PMID: 30855017
ISSN: 0004-0614
CID: 4954002

Incorporating mpMRI biopsy data into established pre-RP nomograms: potential impact of an increasingly common clinical scenario

Leong, Joon Yau; Herrera-Caceres, Jaime O; Goldberg, Hanan; Tham, Elwin; Teplitsky, Seth; Gomella, Leonard G; Fleshner, Neil E; Lallas, Costas D; Trabulsi, Edouard J; Chandrasekar, Thenappan
Background/UNASSIGNED:We examine the practical application of multiparametric MRI (mpMRI) prostate biopsy data using established pre-RP nomograms and its potential implications on RP intraoperative decision-making. We hypothesize that current nomograms are suboptimal in predicting outcomes with mpMRI targeted biopsy (TBx) data. Materials and methods/UNASSIGNED:Patients who underwent mpMRI-based TBx prior to RP were assessed using the MSKCC and Briganti nomograms with the following iterations: (1) Targeted (T) (targeted only), (2) Targeted and Systematic (TS) and (3) Targeted Augmented (TA) (targeted core data; assumed negative systematic cores for 12 total cores). Nomogram outcomes, lymph node involvement (LNI), extracapsular extension (ECE), organ-confined disease (OCD), seminal vesicle invasion (SVI), were compared across iterations. Clinically significant impact on management was defined as a change in LNI risk above or below 2% (Δ2) or 5% (Δ5). Results/UNASSIGNED:A total of 217 men met inclusion criteria. Overall, the TA iteration had more conservative nomogram outcomes than the T. Moreover, TA better predicted RP pathology for all four outcomes when compared with the T. In the entire cohort, Δ2 and Δ5 were 16.6-25.8% and 20.3-39.2%, respectively. In the subset of 190 patients with targeted and systematic cores, TA was a better approximation of TS outcomes than T in 71% (MSKCC) and 82% (Briganti) of patients. Conclusion/UNASSIGNED:In established pre-RP nomograms, mpMRI-based TBx often yield variable and discordant results when compared with systematic biopsies. Future nomograms must better incorporate mpMRI TBx core data. In the interim, augmenting TBx data may serve to bridge the gap.
PMID: 31662795
ISSN: 1756-2872
CID: 4954042

Prevalence and variables associated with an abnormal ankle-brachial index among patients with human immunodeficiency virus/acquired immunodeficiency syndrome

Hinojosa, Carlos A; Nunez-Salgado, Ana E; Anaya-Ayala, Javier E; Laparra-Escareno, Hugo; Ortiz-Lopez, Laura J; Herrera-Caceres, Jaime O; Crabtree-Ramirez, Brenda E; Sierra-Madero, Juan G
Objectives The longer survival of patients with human immunodeficiency virus/acquired immunodeficiency syndrome and the introduction of the highly active antiretroviral therapy have increased the number of chronic conditions; among these, cardiovascular diseases. The aim of this study is to determine patient, disease, and factors associated with peripheral arterial disease in a population of patients with human immunodeficiency virus/acquired immunodeficiency syndrome. Methods A prospective nested case-control study of a cohort of patients with human immunodeficiency virus/acquired immunodeficiency syndrome was conducted in a tertiary medical center in Mexico City. A sample size of 206 patients was calculated. Medical history, relevant laboratory data, peripheral arterial exam, and screening ankle-brachial index tests were obtained. Results The prevalence of abnormal ankle-brachial indexes was 20% (42 patients). Patient's mean age was 44 years ±13. The majority (98.5%) were actively receiving highly active antiretroviral therapy; active smoking was reported in 55 (27%), arterial hypertension and type 2 diabetes mellitus were found in 24 (12%) and 22 (11%) patients. Median time from the human immunodeficiency virus diagnosis was eight years (Interquartile range ±11); the mean CD4 count was 481, with a mean viral load of 13,557 copies (SD ± 69025.27) and 1889.18 (SD ± 9052.77) for patients with normal and abnormal ankle-brachial index and a median of 40 (IQ ± 2). Viral load ( p = 0.04) and number of years with human immunodeficiency virus/acquired immunodeficiency syndrome ( p = 0.04) were significantly associated with abnormal ankle-brachial indexes. Conclusions Abnormal ankle-brachial index seems to be more frequent in Mexican patients with human immunodeficiency virus/acquired immunodeficiency syndrome when compared with the general population at the same age. The most important factors associated with arterial disease were the viral load and the number of years with human immunodeficiency virus/acquired immunodeficiency syndrome.
PMID: 29649953
ISSN: 1708-539x
CID: 4953942