RESUMO
The lack of in vitro prostate cancer models that recapitulate the diversity of human prostate cancer has hampered progress in understanding disease pathogenesis and therapy response. Using a 3D organoid system, we report success in long-term culture of prostate cancer from biopsy specimens and circulating tumor cells. The first seven fully characterized organoid lines recapitulate the molecular diversity of prostate cancer subtypes, including TMPRSS2-ERG fusion, SPOP mutation, SPINK1 overexpression, and CHD1 loss. Whole-exome sequencing shows a low mutational burden, consistent with genomics studies, but with mutations in FOXA1 and PIK3R1, as well as in DNA repair and chromatin modifier pathways that have been reported in advanced disease. Loss of p53 and RB tumor suppressor pathway function are the most common feature shared across the organoid lines. The methodology described here should enable the generation of a large repertoire of patient-derived prostate cancer lines amenable to genetic and pharmacologic studies.
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Técnicas de Cultura , Organoides , Neoplasias da Próstata/patologia , Xenoenxertos , Humanos , Masculino , Metástase Neoplásica/patologia , Organoides/patologia , Farmacologia/métodos , Proteínas Supressoras de Tumor/metabolismoRESUMO
BACKGROUND: Patients with localized, unfavorable intermediate-risk and high-risk prostate cancer have an increased risk of relapse after radical prostatectomy (RP). The authors previously reported on part 1 of this phase 2 trial testing neoadjuvant apalutamide, abiraterone, prednisone, plus leuprolide (AAPL) or abiraterone, prednisone, and leuprolide (APL) for 6 months followed by RP. The results demonstrated favorable pathologic responses (tumor <5 mm) in 20.3% of patients (n = 24 of 118). Herein, the authors report the results of part 2. METHODS: For part 2, patients were randomized 1:1 to receive either AAPL for 12 months (arm 2A) or observation (arm 2B), stratified by neoadjuvant therapy and pathologic tumor classification. The primary end point was 3-year biochemical progression-free survival. Secondary end points included safety and testosterone recovery (>200 ng/dL). RESULTS: Overall, 82 of 118 patients (69%) enrolled in part 1 were randomized to part 2. A higher proportion of patients who were not randomized to adjuvant therapy had a favorable prostatectomy pathologic response (32.3% in nonrandomized patients compared with 17.1% in randomized patients). In the intent-to-treat analysis, the 3-year biochemical progression-free survival rate was 81% for arm 2A and 72% for arm 2B (hazard ratio, 0.81; 90% confidence interval, 0.43-1.49). Of the randomized patients, 81% had testosterone recovery in the AAPL group compared with 95% in the observation group, with a median time to recovery of <12 months in both arms. CONCLUSIONS: In this study, because 30% of patients declined adjuvant treatment, part B was underpowered to detect differences between arms. Future perioperative studies should be biomarker-directed and include strategies for investigator and patient engagement to ensure compliance with protocol procedures.
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Antígeno Prostático Específico , Neoplasias da Próstata , Masculino , Humanos , Leuprolida/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/diagnóstico , Antagonistas de Androgênios/efeitos adversos , Androgênios , Prednisona , Resultado do Tratamento , Recidiva Local de Neoplasia/cirurgia , Prostatectomia/métodos , TestosteronaRESUMO
PURPOSE: Incisional hernias are a frequent complication following robotic radical prostatectomy. Observational data in men undergoing robotic prostatectomy suggest that transverse closure resulted in lower hernia rates than vertical closure. We sought to compare the incidence of incisional hernia after robotic radical prostatectomy after vertical and transverse extraction site closure. MATERIALS AND METHODS: We conducted a clinically integrated, crossover, cluster randomized trial at a single tertiary referral center (January 2016-September 2021) comparing the rate of hernia after transverse vs vertical extraction site excision in 1356 patients treated with minimally invasive radical prostatectomy. The primary outcome was between-group incidence of incisional hernia within 15 months of prostatectomy defined by physical examination and self-reported patient surveys. RESULTS: Overall, 197 (20%) patients developed an incisional hernia within 15 months, 797 did not have an incisional hernia within this period, and 362 had missing outcome data regarding incisional hernia. We found no significant difference in hernia rates between the 2 incision types (absolute between-group difference 1.8%; 95% CI -3.4%, 6.6%; P = .5) in the primary analysis or in the 3 sensitivity analyses. Notably, because of the inclusive definition of hernia used, these data cannot be used as an estimate of the true prevalence of incisional hernia. CONCLUSIONS: Surgeons should choose the incision and closure approach they are most comfortable with when extracting specimens. Studies of modifications to the surgical technique are best conducted as randomized comparisons, and the clinically integrated, crossover, cluster randomized trial allows large trials to be completed at a single center and at low cost. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01407263.
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Estudos Cross-Over , Hérnia Incisional , Prostatectomia , Procedimentos Cirúrgicos Robóticos , Humanos , Prostatectomia/métodos , Prostatectomia/efeitos adversos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Procedimentos Cirúrgicos Robóticos/métodos , Masculino , Pessoa de Meia-Idade , Hérnia Incisional/epidemiologia , Hérnia Incisional/etiologia , Hérnia Incisional/prevenção & controle , Idoso , Incidência , Neoplasias da Próstata/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologiaRESUMO
PURPOSE: There have been conflicting studies on the association between phosphodiesterase type 5 inhibitor (PDE5i) use and biochemical recurrence (BCR) following radical prostatectomy (RP). Our aim was to determine whether PDE5i drug exposure after RP increases the risk of BCR in patients undergoing RP. MATERIALS AND METHODS: An institutional database of prostate cancer patients treated between January 2009 and December 2020 was reviewed. BCR was defined as 2 PSA measurements greater than 0.1 ng/mL. PDE5i exposure was defined using a 0 to 3 scale, with 0 representing never use, 1 sometimes use, 2 regularly use, and 3 routinely use. The risk of BCR with any PDE5i exposure, the quantity of exposure, and the duration of PDE5i exposure were assessed by multivariable Cox proportional hazards models. RESULTS: The sample size included 4630 patients to be analyzed, with 776 patients having BCR. The median follow-up for patients without BCR was 27 (IQR 12, 49) months. Eighty-nine percent reported taking a PDE5i at any time during the first 12 months after RP, and 60% reported doing so for 6 or more months during the year after RP. There was no evidence of an increase in the risk of BCR associated with any PDE5i use (HR 1.05, 95% CI 0.84, 1.31, P = .7) or duration of PDE5i use in the first year (HR 0.98 per 1 month duration, 95% CI 0.96, 1.00, P = .055). Baseline oncologic risk was lower in patients using PDE5i, but differences between groups were small, suggesting that residual confounding is unlikely to obscure any causal association with BCR. CONCLUSIONS: Prescription of PDE5i to men after RP can be based exclusively on quality of life considerations. Patients receiving PDE5is can be reassured that their use does not increase the risk of BCR.
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Inibidores da Fosfodiesterase 5 , Neoplasias da Próstata , Humanos , Masculino , Inibidores da Fosfodiesterase 5/efeitos adversos , Qualidade de Vida , Próstata , Prostatectomia/efeitos adversos , Neoplasias da Próstata/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Antígeno Prostático Específico , Estudos RetrospectivosRESUMO
BACKGROUND: Despite the extensive literature supporting distress screening at relevant transitions of care, the implementation of distress screening remains limited in ambulatory surgery settings. Our multidisciplinary team completed a pilot study to assess the feasibility and acceptability of including a standardized psychosocial assessment, the Distress Thermometer (DT), with the collection of admission vital signs by Patient Care Technicians (PCTs) in patients undergoing oncology surgery. METHODS: We assessed feasibility by the response rate and acceptability through discussions with the PCTs. RESULTS: Of the 189 men who underwent radical prostatectomy at our center, 71 were approached with the DT scale, and all patients who were approached completed the DT with no missing data. The staff reported no issues with data collection. A total of 21/71 (30%; 95% CI 19%, 42%) reported a clinically relevant distress DT ≥ 4. CONCLUSION: Our results demonstrated that incorporating the DT into vital sign collection was feasible, acceptable, and provided a valuable assessment.
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PURPOSE: In response to a nationwide fentanyl shortage, our institution assessed whether changing our first-line postoperative intravenous opioid from fentanyl to hydromorphone impacted patient outcomes. The primary research aim was to evaluate the association between first-line opioid and rapidity of recovery. DESIGN: The study team retrospectively obtained data on all consecutive patients extracted from the electronic medical record. The rapidity of recovery was defined as the time from entry into the postanesthesia care unit to the transition to Phase 2 for ambulatory extended recovery patients and as the length of total postanesthesia care unit stay for outpatients. METHODS: Following intent-to-treat-principles, we tested the association between study period and rapidity of recovery (a priori clinically meaningful difference: 20 minutes) using multivariable linear regression, adjusting for anesthesia type (general vs monitored anesthesia care), American Society of Anesthesiologst physical status (ASA) score (1-2 vs 3-4), age, service, robotic procedure, and surgery start time. FINDINGS: Ambulatory extended recovery patients treated in the hydromorphone period had, on average, a 0.25 minute (95% confidence interval [CI] -6.5, 7.0), nonstatistically significant (P > .9) longer time to transition. For outpatient procedures, those who received hydromorphone had, on average, 8.5-minute longer stays (95% CI 3.7-13, P < .001). Although we saw statistical evidence of an increased risk of resurgery associated with receiving hydromorphone (0.5%; 95% CI -0.1%, 1.0%; P = .039 on univariate analysis), the size of the estimate is clinically and biologically implausible and is most likely a chance finding related either to multiple testing or confounding. CONCLUSIONS: The multidisciplinary team concluded that the increase in postoperative length of stay associated with hydromorphone was not clinically significant and the decrease waste of prefilled syringes outweighed the small potential increased risk of resurgery compared to the shorter-acting fentanyl. We will therefore use hydromorphone moving forward.
Assuntos
Analgésicos Opioides , Fentanila , Hidromorfona , Dor Pós-Operatória , Humanos , Hidromorfona/administração & dosagem , Hidromorfona/uso terapêutico , Fentanila/administração & dosagem , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/uso terapêutico , Masculino , Pessoa de Meia-Idade , Feminino , Estudos Retrospectivos , Dor Pós-Operatória/tratamento farmacológico , Idoso , Neoplasias/cirurgia , Neoplasias/tratamento farmacológico , Procedimentos Cirúrgicos Ambulatórios/métodos , Procedimentos Cirúrgicos Ambulatórios/estatística & dados numéricos , Adulto , Tempo de Internação/estatística & dados numéricosRESUMO
BACKGROUND: Magnetic resonance imaging (MRI)-targeted prostate biopsy (MRI-biopsy) detects high-Grade Group (GG) prostate cancers not identified by systematic biopsy (S-biopsy). However, questions have been raised whether cancers detected by MRI-biopsy and S-biopsy, grade-for-grade, are of equivalent oncologic risk. The authors evaluated the relative oncologic risk of GG diagnosed by S-biopsy and MRI-biopsy. METHODS: This was a retrospective analysis of all patients who had both MRI-biopsy and S-biopsy and underwent with prostatectomy (2014-2022) at Memorial Sloan Kettering Cancer Center. Three logistic regression models were used with adverse pathology as the primary outcome (primary pattern 4, any pattern 5, seminal vesicle invasion, or lymph node involvement). The first model included the presurgery prostate-specific antigen level, the number of positive and negative S-biopsy cores, S-biopsy GG, and MRI-biopsy GG. The second model excluded MRI-biopsy GG to obtain the average risk based on S-biopsy GG. The third model excluded S-biopsy GG to obtain the risk based on MRI-biopsy GG. A secondary analysis using Cox regression evaluated the 12-month risk of biochemical recurrence. RESULTS: In total, 991 patients were identified, including 359 (36%) who had adverse pathology. MRI-biopsy GG influenced oncologic risk compared with S-biopsy GG alone (p < .001). However, if grade was discordant between biopsies, then the risk was intermediate between grades. For example, the average risk of advanced pathology for patients who had GG2 and GG3 on S-biopsy was 19% and 66%, respectively, but the average risk was 47% for patients who had GG2 on S-biopsy and patients who had GG3 on MRI-biopsy. The equivalent estimates for 12-month biochemical recurrence were 5.8%, 15%, and 10%, respectively. CONCLUSIONS: The current findings cast doubt on the practice of defining risk group based on the highest GG. Because treatment algorithms depend fundamentally on GG, further research is urgently required to assess the oncologic risk of prostate tumors depending on detection technique. PLAIN LANGUAGE SUMMARY: Using magnetic resonance imaging (MRI) to help diagnose prostate cancer can help identify more high-grade cancers than using a systematic template biopsy alone. However, we do not know if high-grade cancers diagnosed with the help of an MRI are as dangerous to the patient as high-grade cancers diagnosed with a systematic biopsy. We examined all of our patients who had an MRI biopsy and a systematic biopsy and then had their prostates removed to find out if these patients had risk factors and signs of aggressive cancer (cancer that spread outside the prostate or was very high grade). We found that, if there was a difference in grade between the systematic biopsy and the MRI-targeted biopsy, the risk of aggressive cancer was between the two grades.
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Próstata , Neoplasias da Próstata , Masculino , Humanos , Próstata/diagnóstico por imagem , Próstata/cirurgia , Próstata/patologia , Glândulas Seminais/patologia , Estudos Retrospectivos , Gradação de Tumores , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/cirurgia , Prostatectomia , Imageamento por Ressonância Magnética/métodos , Biópsia Guiada por Imagem/métodosRESUMO
OBJECTIVE: To assess long-term outcomes with robotic versus laparoscopic/thoracoscopic and open surgery for colorectal, urologic, endometrial, cervical, and thoracic cancers. BACKGROUND: Minimally invasive surgery provides perioperative benefits and similar oncological outcomes compared with open surgery. Recent robotic surgery data have questioned long-term benefits. METHODS: A systematic review and meta-analysis of cancer outcomes based on surgical approach was conducted based on Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines using Pubmed, Scopus, and Embase. Hazard ratios for recurrence, disease-free survival (DFS), and overall survival (OS) were extracted/estimated using a hierarchical decision tree and pooled in RevMan 5.4 using inverse-variance fixed-effect (heterogeneity nonsignificant) or random effect models. RESULTS: Of 31,204 references, 199 were included (7 randomized, 23 database, 15 prospective, 154 retrospective studies)-157,876 robotic, 68,007 laparoscopic/thoracoscopic, and 234,649 open cases. Cervical cancer: OS and DFS were similar between robotic and laparoscopic [1.01 (0.56, 1.80), P =0.98] or open [1.18 (0.99, 1.41), P =0.06] surgery; 2 papers reported less recurrence with open surgery [2.30 (1.32, 4.01), P =0.003]. Endometrial cancer: the only significant result favored robotic over open surgery [OS; 0.77 (0.71, 0.83), P <0.001]. Lobectomy: DFS favored robotic over thoracoscopic surgery [0.74 (0.59, 0.93), P =0.009]; OS favored robotic over open surgery [0.93 (0.87, 1.00), P =0.04]. Prostatectomy: recurrence was less with robotic versus laparoscopic surgery [0.77 (0.68, 0.87), P <0.0001]; OS favored robotic over open surgery [0.78 (0.72, 0.85), P <0.0001]. Low-anterior resection: OS significantly favored robotic over laparoscopic [0.76 (0.63, 0.91), P =0.004] and open surgery [0.83 (0.74, 0.93), P =0.001]. CONCLUSIONS: Long-term outcomes were similar for robotic versus laparoscopic/thoracoscopic and open surgery, with no safety signal or indication requiring further research (PROSPERO Reg#CRD42021240519).
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Neoplasias Colorretais , Laparoscopia , Neoplasias da Próstata , Procedimentos Cirúrgicos Robóticos , Masculino , Humanos , Procedimentos Cirúrgicos Robóticos/métodos , Estudos Retrospectivos , Estudos Prospectivos , Neoplasias da Próstata/cirurgia , Pulmão , Neoplasias Colorretais/cirurgia , Laparoscopia/métodosRESUMO
PURPOSE: We compare health-related quality of life using a broad range of validated measures in patients randomized to robotic-assisted radical cystectomy vs open radical cystectomy. METHODS: We retrospectively analyzed patients that had enrolled in both a randomized controlled trial comparing robotic-assisted laparoscopic radical cystectomy vs open radical cystectomy and a separate prospective study of health-related quality of life. The prospective health-related quality of life study collected 14 patient-reported outcomes measures preoperatively and at 3, 6, 12, 18, and 24 months postoperatively. Linear mixed-effects models with an interaction term (study arm×time) were used to test for differences in mean domain scores and differing effects of approach over time, adjusting for baseline scores. RESULTS: A total of 72 patients were analyzed (n=32 robotic-assisted radical cystectomy, n=40 open radical cystectomy). From 3-24 months post-radical cystectomy, no significant differences in mean scores were detected. Mean differences were small in the following European Organization for Research and Treatment of Cancer QLQ-C30 (Core Quality of Life Questionnaire) domains: Global Quality of Life (-1.1; 95% CI -8.4, 6.2), Physical Functioning (-0.4; 95% CI -5.8, 5.0), Role Functioning (0.7; 95% CI -8.6, 10.0). Mean differences were also small in bladder cancer-specific domains (European Organization for Research and Treatment of Cancer QLQ-BLM30 [Muscle Invasive Bladder Cancer Quality of Life Questionnaire]): Body Image (2.9; 95% CI -7.2, 13.1), Urinary Symptoms (8.0; 95% CI -3.0, 19.0). In Urostomy Symptoms, there was a significant interaction term (P < .001) due to lower open radical cystectomy scores at 3 and 24 months. Other domains evaluating urinary, bowel, sexual, and psychosocial health-related quality of life were similar. CONCLUSIONS: Over a broad range of health-related quality of life domains comparing robotic-assisted radical cystectomy and open radical cystectomy, there are unlikely to be clinically relevant differences in the medium to long term, and therefore health-related quality of life over this time period should not be a consideration in choosing between approaches.
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Procedimentos Cirúrgicos Robóticos , Neoplasias da Bexiga Urinária , Humanos , Cistectomia/métodos , Estudos Prospectivos , Estudos Retrospectivos , Qualidade de Vida , Procedimentos Cirúrgicos Robóticos/métodos , Neoplasias da Bexiga Urinária/cirurgia , Resultado do Tratamento , Complicações Pós-Operatórias/cirurgiaRESUMO
PURPOSE: To determine whether ß-microseminoprotein or any of the kallikrein forms in blood-free, total or intact PSA or total hK2-predict metastasis in patients with evidence of detectable levels of PSA in blood after radical prostatectomy. METHOD: We determined marker concentrations in blood from 173 men treated with radical prostatectomy and evidence of detectable levels of PSA in the blood (PSA ≥ 0.05) after surgery between 2014 and 2015 and at least 1 year after any adjuvant therapy. We used Cox regression to determine whether any marker was associated with metastasis using both univariate and multivariable models that included standard clinical predictors. RESULTS: Overall, 42 patients had metastasis, with a median follow-up of 67 months among patients without an event. The levels of intact and free PSA and free-to-total PSA ratio were significantly associated with metastasis. Discrimination was highest for free PSA (c-index: 0.645) and free-to-total PSA ratio (0.625). Only free-to-total PSA ratio remained associated with overall metastasis (either regional or distant) after including standard clinical predictors (p = 0.025) and increased discrimination from 0.686 to 0.697. Similar results were found using distant metastasis as an outcome (p = 0.011; c-index increased from 0.658 to 0.723). CONCLUSION: Our results provide evidence that free-to-total PSA ratio can risk stratifying patients with evidence of detectable levels of PSA in blood after RP. Further research is warranted on the biology of prostate cancer markers in patients with evidence of detectable levels of PSA in blood after radical prostatectomy. Our findings on the free-to-total ratio for predicting adverse oncologic outcomes need to be validated in other cohorts.
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Neoplasias da Próstata , Proteínas Secretadas pela Próstata , Masculino , Humanos , Calicreínas , Antígeno Prostático Específico , Neoplasias da Próstata/patologia , Prostatectomia , Recidiva Local de NeoplasiaRESUMO
BACKGROUND: The lack of evidence-based guidelines for postoperative opioid prescriptions following breast reconstruction contributes to a wide variation in prescribing practices and increases potential for misuse and abuse. METHODS: Between August and December 2019, women who underwent outpatient breast reconstruction were surveyed 7-10 days before (n = 97) and after (n = 101) implementing a standardized opioid prescription reduction initiative. We compared postoperative opioid use, pain control, and refills in both groups. Patient reported outcomes were compared using the BREAST-Q physical wellbeing of the chest domain and a novel symptom Recovery Tracker. RESULTS: Before changes in prescriptions, patients were prescribed a median of 30 pills and consumed three pills (interquartile range [IQR: 1,9]). After standardization, patients were prescribed eight pills and consumed three pills (IQR: 1,6). There was no evidence of a difference in the proportion of patients experiencing moderate to very severe pain on the Recovery Tracker or in the early BREAST-Q physical wellbeing of the chest scores (p = 0.8 and 0.3, respectively). CONCLUSION: Standardizing and reducing opioid prescriptions for patients undergoing reconstructive breast surgery is feasible and can significantly decrease the number of excess pills prescribed. The was no adverse impact on early physical wellbeing, although larger studies are needed to obtain further data.
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Analgésicos Opioides , Mamoplastia , Dor Pós-Operatória , Procedimentos de Cirurgia Plástica , Feminino , Humanos , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/efeitos adversos , Mamoplastia/efeitos adversos , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controle , Dor Pós-Operatória/diagnóstico , Procedimentos de Cirurgia Plástica/efeitos adversos , Padrões de Prática Médica , Prescrições de Medicamentos/normas , Prescrições de Medicamentos/estatística & dados numéricosRESUMO
BACKGROUND: Changes in surgical technique and postoperative care that target improvements in functional outcomes are widespread in the literature. Radical prostatectomy (RP) is one such procedure that has seen multiple advances over the past decade. The objective of this study was to leverage RP as an index case to determine whether practice changes over time produced observable improvements in patient-reported outcomes. METHODS: This study analyzed patients undergoing RP by experienced surgeons at a tertiary care center with prospectively maintained patient-reported outcome data from 2008 to 2019. Four patient-reported urinary function outcomes at 6 and 12 months after RP were defined with a validated instrument: good urinary function (domain score ≥ 17), no incontinence (0 pads per day), social continence (≤1 pad per day), and severe incontinence (≥3 pads per day). Multivariable logistic regressions evaluated changes in outcomes based on the surgical date. RESULTS: Among 3945 patients meeting the inclusion criteria, excellent urinary outcomes were reported throughout the decade but without consistent observable improvements over time. Specifically, there were no improvements in good urinary function at 12 months (P = .087) based on the surgical date, and there were countervailing effects on no incontinence (worsening; P = .005) versus severe incontinence (improving; P = .003). Neither approach (open, laparoscopic, or robotic), nor nerve sparing, nor membranous urethral length mediated changes in outcomes. CONCLUSIONS: In a decade with multiple advances in surgical and postoperative care, there was evidence of improvements in severe incontinence, but no measurable improvements across 3 other urinary outcomes. Although worsening disease factors could contribute to the stable observed outcomes, a more systematic approach to evaluating techniques and implementing patient selection and postoperative care advances is needed. LAY SUMMARY: Although there have been advances in radical prostatectomy over the past decade, consistent observable improvements in postoperative incontinence were not reported by patients. To improve urinary function outcomes beyond the current high standard, the approach to studying innovations in surgical technique needs to be changed, and further development of other aspects of prostatectomy care is needed.
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Laparoscopia , Prostatectomia , Incontinência Urinária , Humanos , Masculino , Próstata , Prostatectomia/efeitos adversos , Prostatectomia/métodos , Incontinência Urinária/epidemiologia , Incontinência Urinária/etiologiaRESUMO
BACKGROUND: Accurate markers for prostate cancer (PC) risk stratification could aid decision-making for initial management strategies. The 4Kscore has an undefined role in predicting outcomes after radical prostatectomy (RP). METHODS: We included 1476 patients with 4Kscore measured prior to RP at two institutions. The 4Kscore was assessed for prediction of adverse pathology at RP and biochemical recurrence (BCR) relative to a clinical model. We pre-specified that all analyses would be assessed in biopsy Grade Group 1 (GG1) or 2 (GG2) PC patients, separately. RESULTS: The 4Kscore increased discrimination for adverse pathology in all patients (delta area under the receiver operative curve (AUC) 0.009, 95% confidence interval (CI) 0.002, 0.016; clinical model AUC 0.767), driven by GG1 (delta AUC 0.040, 95% CI 0.006, 0.073) rather than GG2 patients (delta AUC 0.005, 95% CI -0.012, 0.021). Adding 4Kscore improved prediction of BCR in all patients (delta C-index 0.014, 95% CI 0.007, 0.021; preop-BCR nomogram C-index 0.738), again with larger changes in GG1 than in GG2. CONCLUSIONS: This study validates prior investigations on the use of 4Kscore in men with biopsy-confirmed PC. Men with GG1 PC and a high 4Kscore may benefit from additional testing to guide treatment selection. Further research is warranted regarding the value of the 4Kscore in men with biopsy GG2 PC.
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Calicreínas , Neoplasias da Próstata , Humanos , Masculino , Gradação de Tumores , Próstata/patologia , Antígeno Prostático Específico , Prostatectomia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgiaRESUMO
PURPOSE: Gleason Score 7 prostate cancer comprises a wide spectrum of disease risk, and precise substratification is paramount. Our group previously demonstrated that the total length of Gleason pattern (GP) 4 is a better predictor than %GP4 for adverse pathological outcomes at radical prostatectomy. We aimed to determine the association of GP4 length on prostate biopsy with post-prostatectomy oncologic outcomes. MATERIALS AND METHODS: We compared 4 GP4 quantification methods-including maximum %GP4 in any single core, overall %GP4, total length GP4 (mm) across all cores and length GP4 (mm) in the highest volume core-for prediction of biochemical recurrence-free survival after radical prostatectomy using multivariable Cox proportional hazards regression. RESULTS: A total of 457 men with grade group 2 prostate cancer on biopsy subsequently underwent radical prostatectomy. The 3-year biochemical recurrence-free survival probability was 85% (95% CI 81-88). On multivariable analysis, all 4 GP4 quantification methods were associated with biochemical recurrence-maximum %GP4 (HR=1.30; 95% CI 1.07-1.59; p=0.009), overall %GP4 (HR=1.61; 95% CI 1.21-2.15; p=0.001), total length GP4 (HR=2.48; 95% CI 1.36-4.52; p=0.003) and length GP4 in highest core (HR=1.32; 95% CI 1.11-1.57; p=0.001). However, we were unable to identify differences between methods of quantification with a relatively low event rate. CONCLUSIONS: These findings support further studies on GP4 quantification in addition to the ratio of GP3 and GP4 to classify prostate cancer risk. Research should also be conducted on whether GP4 quantification could provide a surrogate endpoint for disease progression for trials in active surveillance.
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Neoplasias da Próstata , Biópsia , Humanos , Masculino , Gradação de Tumores , Recidiva Local de Neoplasia/patologia , Próstata/patologia , Próstata/cirurgia , Antígeno Prostático Específico , Prostatectomia , Neoplasias da Próstata/patologiaRESUMO
PURPOSE: The impact of germline mutations associated with hereditary cancer syndromes in patients on active surveillance (AS) for prostate cancer is poorly defined. We examined the association between family history of prostate cancer (FHP) or family history of cancer (FHC) and risk of progression or adverse pathology at radical prostatectomy (RP) in patients on AS. MATERIALS AND METHODS: Patients on AS at a single tertiary-care center between 2000-2019 were categorized by family history. Disease progression was defined as an increase in Gleason grade on biopsy. Adverse pathology was defined as upgrading/upstaging at RP. Multivariable Cox and logistic regression models were used to assess association between family history and time to progression or adverse pathology, respectively. RESULTS: Among 3,211 evaluable patients, 669 (21%) had FHP, 34 (1%) had FHC and 95 (3%) had both; 753 progressed on AS and 481 underwent RP. FHP was associated with increased risk of progression (HR 1.31; 95% CI, 1.11-1.55; p=0.002) but FHC (HR 0.67; 95% CI, 0.30-1.50; p=0.3) or family history of both (HR 1.22; 95% CI, 0.81-1.85; p=0.3) were not. FHP, FHC or both were not associated with adverse pathology at RP (p >0.4). CONCLUSIONS: While FHP was associated with an increased risk of progression on AS, wide confidence intervals render this outcome of unclear clinical significance. FHC was not associated with risk of progression on AS. In the absence of known genetically defined hereditary cancer syndrome, we suggest FHP and/or FHC should not be used as a sole trigger to preclude patients from enrolling on AS.
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Neoplasias da Próstata , Conduta Expectante , Humanos , Masculino , Gradação de Tumores , Antígeno Prostático Específico , Prostatectomia , Neoplasias da Próstata/patologiaRESUMO
PURPOSE: Many patients will experience symptoms in the initial days after radical prostatectomy (RP), but early patient-reported symptoms have not been well characterized. Our objective was to illustrate the pattern of symptoms experienced after RP and the relation of severe symptoms to postoperative complications. MATERIALS AND METHODS: In 2016, electronic patient-reported symptom monitoring began at our institution's ambulatory surgery center. We retrospectively reviewed patients treated with minimally invasive RP who were sent a daily questionnaire completed using a web interface until postoperative day 10. Severe symptoms automatically generate a "yellow alert," which messages the clinic, while very severe symptoms generate a "red alert," additionally prompting the patient to call. We summarized rates of moderate-to-very severe symptoms and fit local polynomial regressions. We compared rates of 30-day or 90-day complications (grade ≥2) based on the presence of alert symptoms. RESULTS: Of 2,266 men undergoing RP, 1,942 (86%) completed surveys. Among moderate-to-very severe symptom levels, pain (72%) and dyspnea (11%) were most common. Pain, nausea and dyspnea consistently decreased over time; fever and vomiting had a flat pattern. In patients experiencing red-alert symptoms, we observed a higher risk of 30-day complications, but rates were low and differences between groups were nonsignificant (2.9% vs 1.9%; difference 1.1%; 95% CI -1.3-3.5; p=0.3). Results were similar examining 90-day complications. CONCLUSIONS: While symptoms are common after RP, substantial improvements occur over the first 10 days. Severe or very severe symptoms conferred at most a small absolute increase in complication risk, which should be reassuring to patients and clinicians.
Assuntos
Laparoscopia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Prostatectomia/efeitos adversos , Neoplasias da Próstata/cirurgia , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Próstata/patologia , Próstata/cirurgia , Prostatectomia/métodos , Neoplasias da Próstata/patologia , Estudos Retrospectivos , Medição de Risco/métodos , Índice de Gravidade de Doença , Fatores de TempoRESUMO
OBJECTIVES: To analyse the risk of uretero-enteric anastomotic stricture in patients randomised to open (ORC) or robot-assisted radical cystectomy (RARC) with extracorporeal urinary diversion. PATIENTS AND METHODS: We included 118 patients randomised to RARC (n = 60) or ORC (n = 58) at a single, high-volume institution from March 2010 to April 2013. Urinary diversion was performed by experienced open surgeons. Stricture was defined as non-malignant obstruction on imaging, corroborated by clinical status, and requiring procedural intervention. The risk of stricture within 1 year was compared between groups using Fisher's exact test. RESULTS: In all, 58 and 60 patients were randomised to RARC and ORC, respectively. We identified five strictures, all in the ORC group. In patients with ≥1 year of follow-up, the increase in risk of stricture from open surgery was 9.3% (95% confidence interval 1.5%, 17%). Of the five strictures, three were managed endoscopically while two required open revision. There was no evidence that perioperative Grade 3-5 complications were associated with development of a stricture (P = 1) and no evidence of a difference in 24-month estimated glomerular filtration rate between arms (P = 0.15). CONCLUSIONS: In this study at a high-volume centre, RARC with extracorporeal urinary diversion achieved excellent ureteric anastomotic outcomes. Purported increased risk of stricture is not a reason to avoid RARC. Future research should examine the impact of different surgical techniques and operator experience on the risk of stricture, especially as more intracorporeal diversions are performed.
Assuntos
Procedimentos Cirúrgicos Robóticos , Robótica , Neoplasias da Bexiga Urinária , Derivação Urinária , Humanos , Cistectomia/efeitos adversos , Cistectomia/métodos , Constrição Patológica/etiologia , Constrição Patológica/cirurgia , Neoplasias da Bexiga Urinária/patologia , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Procedimentos Cirúrgicos Robóticos/métodos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Resultado do Tratamento , Derivação Urinária/efeitos adversos , Derivação Urinária/métodosRESUMO
PURPOSE: We aimed to report the morbidity profile of salvage radical prostatectomy (SRP) after radiotherapy failure and assess the impact of minimally invasive surgery (MIS) on postoperative complications and functional outcomes. MATERIALS AND METHODS: Between 1985 and 2019, a total of 293 patients underwent SRP; 232 underwent open SRP; and 61 underwent laparoscopic SRP with or without robotic assistance. Complications were recorded and classified into standardized categories per the Clavien-Dindo classification. RESULTS: Twenty-nine patients (10%) experienced grade 3 complications within 30 days, 22 (9.5%) after open and 7 (11%) after MIS (p = 0.6). Between 30 and 90 days after surgery, 7.3% of patients in the open group and 10% in the MIS group had grade 3 complications (p = 0.5). The most common complication was bladder neck contracture (BNC), representing 40% of the 30-90 day complications. Within one year of SRP, 81 patients (31%, 95% CI 25%, 37%) developed BNC; we saw non-significant lower rates in MIS (25 vs 32%; p = 0.4). Functional outcomes were poor after SRP and showed no difference between open and MIS groups for urinary continence (16 vs 18%, p = 0.7) and erectile function (7 vs 13%, p = 0.4). 5 year cancer-specific survival and overall survival was 95% and 88% for the entire cohort, respectively. CONCLUSIONS: Our outcomes suggest poor functional recovery after SRP, regardless of the operative approach. Currently there is no evidence favoring the use of open or MIS approach. Further studies are required to ensure comparable outcomes between these approaches.
Assuntos
Prostatectomia , Terapia de Salvação , Humanos , Masculino , Procedimentos Cirúrgicos Minimamente Invasivos , Morbidade , Próstata/cirurgia , Resultado do TratamentoRESUMO
PURPOSE: Prophylactic antibiotics are routinely given at the time of catheter removal post-radical prostatectomy (RP). The low rate of infectious complications entails that large sample sizes are required for randomized controlled trials, a challenge given the cost of standard randomized controlled trials. We evaluated infectious complications associated with 1 vs 3 days of prophylactic antibiotics at the time of catheter removal post-RP using a novel, clinically integrated trial with randomization at the surgeon level. MATERIALS AND METHODS: Surgeons were cluster randomized for periods of 3 months to prescribe 1-day vs 3-day regimen of prophylactic antibiotics at the time of catheter removal. The primary end point was an infectious complication as routinely captured by nursing phone call within 10 days of catheter removal and defined as positive urine cultures (≥105 CFU) and at least 1 of the following symptoms: fever (>38°C), urgency, frequency, dysuria or suprapubic tenderness. RESULTS: A total of 824 patients were consented and underwent RP with, respectively, 389 and 435 allocated to 1-day and 3-day antibiotics, predominantly ciprofloxacin. Accrual was achieved within 3 years: 95% vs 88% of patients received the allocated 3-day vs 1-day antibiotic regimen. There were 0 urinary tract infections (0%) in the 1-day regimen and 3 urinary tract infections (0.7%) in the 3-day regimen, meeting our prespecified criterion for declaring the 1-day regimen to be noninferior. CONCLUSIONS: A clinically integrated trial using cluster randomization accrued rapidly with no important logistical problems and negligible burden on surgeons. If surgeons choose to prescribe empiric prophylactic antibiotics after catheter removal following RP, then the duration should not exceed 1 day.
Assuntos
Antibioticoprofilaxia/métodos , Infecções Relacionadas a Cateter/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Prostatectomia/efeitos adversos , Infecções Urinárias/epidemiologia , Idoso , Antibacterianos/administração & dosagem , Antibioticoprofilaxia/estatística & dados numéricos , Infecções Relacionadas a Cateter/microbiologia , Infecções Relacionadas a Cateter/prevenção & controle , Catéteres/efeitos adversos , Ciprofloxacina/administração & dosagem , Estudos Cross-Over , Remoção de Dispositivo/efeitos adversos , Esquema de Medicação , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/microbiologia , Complicações Pós-Operatórias/prevenção & controle , Próstata/cirurgia , Neoplasias da Próstata/cirurgia , Fatores de Tempo , Resultado do Tratamento , Cateterismo Urinário/efeitos adversos , Cateterismo Urinário/instrumentação , Infecções Urinárias/microbiologia , Infecções Urinárias/prevenção & controleRESUMO
PURPOSE: This multicenter randomized phase 2 trial investigates the impact of intense androgen deprivation on radical prostatectomy pathologic response and radiographic and tissue biomarkers in localized prostate cancer (NCT02903368). MATERIALS AND METHODS: Eligible patients had a Gleason score ≥4+3=7, prostate specific antigen >20 ng/mL or T3 disease and lymph nodes <20 mm. In Part 1, patients were randomized 1:1 to apalutamide, abiraterone acetate, prednisone and leuprolide (AAPL) or abiraterone, prednisone, leuprolide (APL) for 6 cycles (1 cycle=28 days) followed by radical prostatectomy. Surgical specimens underwent central review. The primary end point was the rate of pathologic complete response or minimum residual disease (minimum residual disease, tumor ≤5 mm). Secondary end points included prostate specific antigen response, positive margin rate and safety. Magnetic resonance imaging and tissue biomarkers of pathologic outcomes were explored. RESULTS: The study enrolled 118 patients at 4 sites. Median age was 61 years and 94% of patients had high-risk disease. The combined pathologic complete response or minimum residual disease rate was 22% in the AAPL arm and 20% in the APL arm (difference: 1.5%; 1-sided 95% CI -11%, 14%; 1-sided p=0.4). No new safety signals were observed. There was low concordance and correlation between posttherapy magnetic resonance imaging assessed and pathologically assessed tumor volume. PTEN-loss, ERG positivity and presence of intraductal carcinoma were associated with extensive residual tumor. CONCLUSIONS: Intense neoadjuvant hormone therapy in high-risk prostate cancer resulted in favorable pathologic responses (tumor <5 mm) in 21% of patients. Pathologic responses were similar between treatment arms. Part 2 of this study will investigate the impact of adjuvant hormone therapy on biochemical recurrence.