Implementation and Validation of an Automated, Longitudinal Robotic Surgical Evaluation and Feedback Program at a High-volume Center and Impact on Training.

Background: Surgical education lacks a standardized, proficiency-based approach to evaluation and feedback. Objective: To assess the implementation and reception (ie, feasibility) of an automated, standardized, longitudinal surgical skill assessment and feedback system, and identify baseline trainee (resident and fellow) characteristics associated with achieving proficiency in robotic surgery while learning robotic-assisted laparoscopic prostatectomy. Design setting and participants: A quality improvement study assessing a pilot of a surgical experience tracking program was conducted over 1 yr. Participants were six fellows, eight residents, and nine attending surgeons at a tertiary cancer center. Intervention: Trainees underwent baseline self-assessment. After each surgery, an evaluation was completed independently by the trainee and attending surgeons. Performance was rated on a five-point anchored Likert scale (trainees were considered "proficient" when attending surgeons' rating was ≥4). Technical skills were assessed using the Global Evaluative Assessment of Robotic Skills (GEARS) and Prostatectomy Assessment and Competency Evaluation (PACE). Outcome measurements and statistical analysis: Program success and utility were assessed by evaluating completion rates, evaluation completion times, and concordance rates between attending and trainee surgeons, and exit surveys. Baseline characteristics were assessed to determine associations with achieving proficiency. Results and limitations: Completion rates for trainees and attending surgeons were 72% and 77%, respectively. Fellows performed more steps/cases than residents (median [interquartile range]: 5 [3-7] and 3 [2-4], respectively; p < 0.01). Prior completion of robotics or laparoscopic skill courses and surgical experience measures were associated with achieving proficiency in multiple surgical steps and GEARS domains. Interclass correlation coefficients on individual components were 0.27-0.47 on GEARS domains. Conclusions: An automated surgical experience tracker with structured, longitudinal evaluation and feedback can be implemented with good participation and minimal participant time commitment, and can guide curricular development in a proficiency-based education program by identifying modifiable factors associated with proficiency, individualizing education, and identifying improvement areas within the education program. Patient summary: An automated, standardized, longitudinal surgical skill assessment and feedback system can be implemented successfully in surgical education settings and used to inform education plans and predict trainee proficiency.

Changes in the Perioperative Management and Outcomes of Patients With Upper Tract Urothelial Carcinoma Undergoing Radical Nephroureterectomy at Memorial Sloan Kettering Cancer Center: Over 20 Years of Experience.

INTRODUCTION: We evaluated surgical trends, perioperative management evolution, and oncologic outcomes in patients who underwent radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) at a tertiary cancer center over a 24-year period. METHODS: Between 1995 and 2018, we evaluated 743 consecutive patients with UTUC who underwent RNU. Generalized additive models were used to estimate the associations between date of surgery and continuous outcomes using a linear model, dichotomous outcomes using a logit link, categorical outcomes using multinomial models, and 2- and 5-year survival outcomes using Cox proportional hazards models. RESULTS: Over the study period, preoperative diagnostic endoscopic biopsies increased from 10% to 66%, along with the proportion of patients who underwent RNU for high-grade disease from 55% to 91%. The rate of open RNU declined from 100% to 56% with a rise in minimally invasive approaches. Median lymph node yield increased with more retroperitoneal lymph node dissections performed. Neoadjuvant chemotherapy utilization increased with a contemporary utilization rate of 32%, coinciding with an increase in pT0 rate from 2% to 8%. Cancer-specific survival probabilities improved over the study period, while metastasis-free and overall survival remained stable. CONCLUSIONS: We found several changes in treatment patterns and outcomes for patients with UTUC over the past 2 decades. How individual alterations in management factors, such as patient selection, perioperative chemotherapy, lymphadenectomy, and salvage therapies, impact patient outcomes is challenging in the setting of multiple overlapping practice changes for this rare disease and warrants further investigation.

Do Phosphodiesterase Type 5 Inhibitors Increase the Risk of Biochemical Recurrence After Radical Prostatectomy?

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.

Comparison of salvage radical prostatectomy vs. salvage ablation therapy for biopsy-proven radio-recurrent localized prostate cancer.

INTRODUCTION: Radiation therapy for prostate cancer is associated with a 15-20% five-year recurrence rate. Patients with recurrence in the prostate only are candidates for salvage local therapies; however, there is no consensus on modality. This study uses registries at Memorial Sloan Kettering Cancer Center (MSKCC) and University of Western Ontario (UWO) to compare the oncologic outcomes of salvage radical prostatectomy (SRP) and salvage ablation (SA). METHODS: A total of 444 patients were available for analysis. Due to intergroup differences, propensity score methodology was used and identified 378 patients with more comparable pre-salvage prostate-specific antigen (PSA), Gleason score, and primary radiation treatment. Patients underwent SRP at MSKCC and SA at UWO. RESULTS: Of the 378 patients, 48 died of disease, with a 6.0-year median (interquartile range [IQR] 3.0, 9.7) followup among survivors; 88 developed metastases, with a median 4.6-year (IQR 2.3, 7.9) followup among metastasis-free survivors. There was a non-significantly higher rate of cancer-specific (hazard ratio [HR ] 1.02, 95% confidence interval [CI] 0.51, 2.06, p=0.9) and improved metastasis-free survival (HR 0.71, 95% CI 0.44, 1.13, p=0.15) among patients undergoing SA compared to patients undergoing SRP. There were 143 patients who received hormonal therapy, with higher rates of androgen deprivation therapy (ADT) in SA (HR 1.42, 95% CI 0.97, 2.08, p=0.068), although this did not meet conventional levels of significance. CONCLUSIONS: This propensity score analysis of salvage therapy for radio-recurrent prostate cancer identified no statistically significant differences in oncologic outcome between SRP and SA; however, there was evidence of a lower risk of ADT in the cohort undergoing SRP. Given they are both potentially curative therapies, these treatments are viable options for men with clinically localized, radio-recurrent prostate cancer rather than ADT alone. Future research may further elucidate subpopulations that may be more amenable to either SRP or SA.

Adding a Coefficient for Race to the 4Kscore Improves Calibration for Black Men.

PURPOSE: Black men face a higher incidence of high-risk prostate cancer (PCa) compared with non-Black men. While the 4Kscore is a widely utilized commercial test for PCa risk assessment, it does not currently account for racial differences. The aim of this study is to describe and validate a prespecified race coefficient for the 4Kscore with the goal of improving the accuracy of this test for Black men. MATERIALS AND METHODS: Using data from 85 Black men from the initial US prospective validation study, a race coefficient of 0.6 on the log-odds scale was prespecified. We calculated discrimination, calibration, and clinical utility of the 4Kscore with and without this coefficient for Black race in our primary analysis cohort of 205 Black men undergoing biopsy for PCa in a Veterans Affairs (VA) institution. We performed a sensitivity analysis using a combined cohort from the US prospective validation and the VA studies. RESULTS: The mean probability of high-grade PCa from the 4Kscore in the primary cohort increased from 25% to 37% with race coefficient addition. Incorporating the race coefficient improved 4Kscore's calibration in Black men, with consequent improvements in clinical utility based on decision curve analysis. Model discrimination was maintained (AUC 0.825 vs 0.828, P = .14) in the combined cohort of Black and non-Black men from the US prospective and VA studies and the calibration remained largely unchanged. CONCLUSIONS: Incorporating a prespecified coefficient for Black race improved calibration and clinical utility of the 4Kscore among Black men and should be added to the 4Kscore.

Accuracy of a faecal immunochemical test in patients under colonoscopy surveillance of colorectal adenoma and cancer.

Background: Surveillance of colorectal neoplasia place great strain on colonoscopy resources, and faecal immunochemical tests (FIT) are under-investigated for this purpose. The aim of this study was to report the outcome of FIT among patients scheduled for post-polypectomy and post-resection colorectal cancer (CRC) surveillance. Methods: Patients scheduled for colonoscopy surveillance at five endoscopy units in mid-Sweden in 2016-2020 were eligible. They provided a faecal sample from 2 separate days, which were analysed by iFOBT QuikRead go® (Aidian Oy). Both the colonoscopies, and the FIT analyses were conducted by staff blinded to the other. Results: Out of 216 included patients, 157 (73%) underwent both a complete colonoscopy and had at least one FIT analysed prior to the examination. The indication for surveillance was previous adenoma in 69 (44%) and post-resection CRC in 88 (56%) patients. Two (1%) in the CRC surveillance group were diagnosed with a metachronous CRC, whereas 49 (56%) patients in the CRC surveillance, and 17 (25%) in the adenoma group had no pathology identified at colonscopy (P < 0.001). The proportion of patients diagnosed with adenomas requiring surveillance according to European Society of Gastrointestinal Society (ESGE) guidelines 2020 was 6 (7%) in the post-CRC resection versus 7 (10%) in the adenoma surveillance group (P = 0.4). Based on one FIT and at cut-off 10 µg Hb/g, sensitivity for CRC was 100%, specificity 83% (95% confidence interval [CI]: 77-89), Positive Predictive Value (PPV) 7% (-2 to 16) and Negative Predictive Value (NPV) 100%. All patients with an adenoma requiring surveillance had a FIT below this cut-off. Adding a second FIT decreased the specificity. Conclusion: Larger studies to evaluate the accuracy and consequences of using FIT for surveillance of colorectal neoplasia are needed. FIT may be more interesting for post-resection CRC surveillance than follow-up of adenoma.

Predictive value of kallikrein forms and ß-microseminoprotein in blood from patients with evidence of detectable levels of PSA after radical prostatectomy.

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.

The effect of the da Vinci® Vessel Sealer on robot-assisted laparoscopic prostatectomy complications.

The da Vinci® Vessel Sealer is a major contributor to the total cost of robot-assisted laparoscopic prostatectomy (RALP). We aimed to assess whether the use of the Vessel Sealer is associated with better surgical outcomes in a population of patients that underwent RALP with lymphadenectomy. We tested whether the use of the Vessel Sealer is associated with the development of lymphocele and/or other surgical outcomes. Most surgeons used the Vessel Sealer in almost all or almost no patients. Thus, to avoid the potential confounding variable of surgeon skill, we performed the initial analyses using data from a single surgeon who changed practice over time, and then using the entire population. Overall, the Vessel Sealer was used in 500 (36%) RALPs. Surgeon 1 performed 492 surgeries, and used the Vessel Sealer in 191 (39%). The Vessel Sealer was not associated with better surgical outcomes in patients operated on by Surgeon 1. The odds ratio for development of lymphocele was 1.95 (95% confidence interval [CI] 0.57-6.75). In the entire population, use of the sealer was significantly associated with a very small reduction of blood loss (22 cc, CI 13-30) but with a 32-min increase in the operating room time (CI 26-37). Use of the Vessel Sealer will have, at best, a very small effect on RALP outcomes that is of highly questionable relevance given its cost. In light of these results, the Vessel Sealer will only be used at our institution in the context of clinical trials.

Feeling safe or falling through the cracks-Patients' experiences of healthcare in cirrhosis illness: A qualitative study.

INTRODUCTION: Patients with cirrhosis have a long-lasting relationship with medical personnel. Hierarchy in the healthcare contacts and feeling stigmatised may affect the patient's interactions with these care providers. Despite healthcare professionals' awareness of patients' increased self-care needs, patients report getting insufficient information and support. The patients' expectations and experiences of interacting with healthcare professionals in cirrhosis care is hence a research area that needs further investigation. PURPOSE: To capture patients' descriptions of healthcare experiences in relation to cirrhosis illness. MATERIAL AND METHODS: Data comprise semi-structured interviews (N = 18) and open-ended questionnaire responses (N = 86) of patients with cirrhosis. Braun and Clarke's thematic analysis process was used, including both semantic and inductive elements. The study is reported following the COREQ guidelines. FINDINGS: The analysis resulted in two themes: 1) Struggle to be in a dialogue and 2) Being helped or harmed. Six sub-themes were identified concerning aspects of experiences within each theme during the analysis. These sub-themes included: 'getting information', 'being involved', 'being perceived as a person', 'enduring care', 'feeling lost in the healthcare organisation', and 'not being taken care of'. CONCLUSIONS: Patients with cirrhosis express concerns regarding where to turn in the continuum of cirrhosis care. They emphasise the importance of being involved in the dialogue with the healthcare professional, to be perceived as a person with a unique need to be informed. The healthcare organisation and continuity of care are either viewed as confusing or as helping to shape a safe and trustful contact, which was an important difference in feeling helped or harmed. Hence, patients wished for improved collaboration with healthcare professionals and to receive increased information about their disease. Person-centred communication in nurse-led clinics may increase patient satisfaction and prevent patients from falling through the cracks.

Does a brief surgeon training in negotiation theory principles decrease rates of contralateral prophylactic mastectomy?

PURPOSE: Despite the lack of any oncologic benefit, contralateral prophylactic mastectomy (CPM) use among women with unilateral breast cancer is increasing. This patient-driven trend is influenced by fear of recurrence and desire for peace of mind. Traditional educational strategies have been ineffective in reducing CPM rates. Here we employ training in negotiation theory strategies for counseling and determine the effect on CPM rates. METHODS: In consecutive patients with unilateral breast cancer treated with mastectomy from 05/2017 to 12/2019, we examined CPM rates before and after a brief surgeon training in negotiation skills. This comprised a systematic framework for patient counseling utilizing early setting of the default option, leveraging social proof, and framing. RESULTS: Among 2144 patients, 925 (43%) were treated pre-training and 744 (35%) post-training. Those treated in the 6-month transition period were excluded (n = 475, 22%). Median patient age was 50 years; most patients had T1-T2 (72%), N0 (73%), and estrogen receptor-positive (80%) tumors of ductal histology (72%). The CPM rate was 47% pre-training versus 48% post-training, with an adjusted difference of -3.7% (95% CI -9.4 to 2.1, p = 0.2). In a standardized self-assessment survey, all 15 surgeons reported a high baseline use of negotiation skills and no significant change in conversational difficulty with the structured approach. CONCLUSION: Brief surgeon training did not affect self-reported use of negotiation skills or reduce CPM rates. The choice of CPM is a highly individual decision influenced by patient values and decision styles. Further research to identify effective strategies to minimize surgical overtreatment with CPM is needed.

Health-related Quality of Life After Robotic-assisted vs Open Radical Cystectomy: Analysis of a Randomized Trial.

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.

Final Results of a Phase I Trial of WST-11 (TOOKAD Soluble) Vascular-targeted Photodynamic Therapy for Upper Tract Urothelial Carcinoma.

PURPOSE: Vascular-targeted photodynamic therapy with the intravascular photosensitizing agent padeliporfin (WST-11/TOOKAD-Soluble) has demonstrated therapeutic efficacy as an ablative treatment for localized cancer with potential adaptation for endoscopic management of upper tract urothelial carcinoma. This Phase I trial (NCT03617003) evaluated the safety of vascular-targeted photodynamic therapy with WST-11 in upper tract urothelial carcinoma. MATERIALS AND METHODS: Nineteen patients underwent up to 2 endoscopic vascular-targeted photodynamic therapy treatments, with follow-up for up to 6 months. Patients who had residual or recurrent upper tract urothelial carcinoma (any grade/size) failing prior endoscopic treatment or unable or unwilling to undergo surgical resection were eligible for inclusion. The primary endpoint was to identify the maximally tolerated dose of laser light fluence. A dose escalation model was employed, with increasing light fluence (100-200 mW/cm) using a modified continual reassessment method. The secondary endpoint was treatment efficacy, defined by absence of visible tumor and negative urine cytology 30 days posttreatment. RESULTS: Fourteen (74%) patients received the maximally tolerated dose of 200 mW/cm, 2 (11%) of whom experienced a dose-limiting toxicity. The initial 30-day treatment response rate was 94% (50% complete, 44% partial). Eight patients underwent a second treatment, with a final observed 68% complete response rate. Leading toxicities were flank pain (79%) and hematuria (84%), which were transient. No ureteral strictures associated with treatment were identified during follow-up. CONCLUSIONS: Vascular-targeted photodynamic therapy with WST-11 has an acceptable safety profile with strong potential as an effective, kidney-sparing endoscopic management option for upper tract urothelial carcinoma. The recently initiated multicenter Phase 3 ENLIGHTED trial (NCT04620239) is expected to provide further evidence on this therapy.

Association of smoking history on health-related quality of life in patients undergoing radical cystecomy.

PURPOSE: Radical cystectomy (RC) has the potential to impact health-related quality of life (HRQOL). Many patients who undergo RC are current or former smokers. To better inform preoperative patient counseling, we examined the association between smoking status and HRQOL after RC. MATERIALS AND METHODS: A secondary analysis was performed on a prospective, longitudinal study (2008-2014) examining HRQOL in patients undergoing RC for bladder cancer. We analyzed 12 validated patient-reported outcome measures that focused on functional, symptomatic, psychosocial, and global HRQOL domains. Measures were collected pre-operatively and 3-, 6-, 12-, 18-, and 24-months postoperatively. For each HRQOL domain, we estimated the mean domain scores using a generalized estimation equation linear regression model. Each model included survey time, smoking status, and time-smoking interaction as covariates. Pairwise comparisons of current, former, and never smokers were estimated from the models. RESULTS: Of the 411 patients available for analysis, 29% (n = 119) never smoked, 59% (n = 244) were former smokers, and 12% (n = 48) were current smokers. Over the follow-up period, never smokers compared to current smokers had better global QOL scores (mean difference = +8.9; 95% CI 1.3-16; p = 0.023) and lower pain levels (mean difference = -10; 95% CI -19 to -0.54; p = 0.036). Compared to current smokers, former smokers had marginal improvements in global QOL (+6.9 points) and pain (-7.5 points) during the follow-up period. CONCLUSIONS: Current smokers reported worse HRQOL recovery in the 24-months after RC. These findings can be used to counsel patients who smoke on recovery expectations.

Multicenter Phase II Clinical Trial of Gemcitabine and Cisplatin as Neoadjuvant Chemotherapy for Patients With High-Grade Upper Tract Urothelial Carcinoma.

PURPOSE: Neoadjuvant chemotherapy (NAC) has proven survival benefits for patients with invasive urothelial carcinoma of the bladder, yet its role for upper tract urothelial carcinoma (UTUC) remains undefined. We conducted a multicenter, single-arm, phase II trial of NAC with gemcitabine and split-dose cisplatin (GC) for patients with high-risk UTUC before extirpative surgery to evaluate response, survival, and tolerability. METHODS: Eligible patients with defined criteria for high-risk localized UTUC received four cycles of split-dose GC before surgical resection and lymph node dissection. The primary study end point was rate of pathologic response (defined as < ypT2N0). Secondary end points included progression-free survival (PFS), overall survival (OS), and safety and tolerability. RESULTS: Among 57 patients evaluated, 36 (63%) demonstrated pathologic response (95% CI, 49 to 76). A complete pathologic response (ypT0N0) was noted in 11 patients (19%). Fifty-one patients (89%) tolerated at least three complete cycles of split-dose GC, 27 patients (47%) tolerated four complete cycles, and all patients proceeded to surgery. With a median follow up of 3.1 years, 2- and 5-year PFS rates were 89% (95% CI, 81 to 98) and 72% (95% CI, 59 to 87), while 2- and 5-year OS rates were 93% (95% CI, 86 to 100) and 79% (95% CI, 67 to 94), respectively. Pathologic complete and partial responses were associated with improved PFS and OS compared with nonresponders (≥ ypT2N any; 2-year PFS 100% and 95% v 76%, P < .001; 2-year OS 100% and 100% v 80%, P < .001). CONCLUSION: NAC with split-dose GC for high-risk UTUC is a well-tolerated, effective therapy demonstrating evidence of pathologic response that is associated with favorable survival outcomes. Given that these survival outcomes are superior to historical series, these data support the use of NAC as a standard of care for high-risk UTUC, and split-dose GC is a viable option for NAC.

A data processing pipeline for the AACR project GENIE biopharma collaborative data with the {genieBPC} R package.

MOTIVATION: Data from the American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange Biopharma Collaborative (GENIE BPC) represent comprehensive clinical data linked to high-throughput sequencing data, providing a multi-institution, pan-cancer, publicly available data repository. GENIE BPC data provide detailed demographic, clinical, treatment, genomic and outcome data for patients with cancer. These data result in a unique observational database of molecularly characterized tumors with comprehensive clinical annotation that can be used for health outcomes and precision medicine research in oncology. Due to the inherently complex structure of the multiple phenomic and genomic datasets, the use of these data requires a robust process for data integration and preparation in order to build analytic models. RESULTS: We present the {genieBPC} package, a user-friendly data processing pipeline to facilitate the creation of analytic cohorts from the GENIE BPC data that are ready for clinico-genomic modeling and analyses. AVAILABILITY AND IMPLEMENTATION: {genieBPC} is available on CRAN and GitHub.

Oncologic outcomes of patients with lymph node invasion at prostatectomy and post-prostatectomy biochemical persistence.

BACKGROUND: Pathologic nodal invasion at prostatectomy is frequently associated with persistently elevated prostate-specific antigen (PSA) and with increased risk of disease recurrence. Management strategies for these patients are poorly defined. We aimed to explore the long-term oncologic outcomes and patterns of disease progression. METHODS: We included men treated between 2000 and 2017 who had lymph node invasion at radical prostatectomy and persistently detectable prostate-specific antigen post-prostatectomy. Postoperative imaging and management strategies were collated. Patterns of recurrence and probability of metastasis-free survival, prostate cancer-specific survival, and overall survival (OS) were assessed. RESULTS: Among our cohort of 253 patients, 126 developed metastasis. Twenty-five had a positive scan within 6 months of surgery; of these, 15 (60%) had a nodal metastasis, 10 (40%) had a bone metastasis, and 4 (16%) had local recurrence. For metastasis-free survival, 5- and 10-year probabilities were 52% (95% CI 45%, 58%) and 37% (95% CI 28%, 46%), respectively. For prostate cancer-specific survival, 5- and 10-year probabilities were 89% (95% CI 84%, 93%) and 67% (95% CI 57%, 76%), respectively. A total of 221 patients proceeded to hormonal deprivation treatment alone. Ten patients received postoperative radiotherapy. CONCLUSIONS: Biochemical persistence in patients with lymph node invasion is associated with high risk of disease progression and reduced prostate cancer-specific survival. Management was hindered by the limitation of imaging modalities utilized during the study period in accurately detecting residual disease. Novel molecular imaging may improve staging and help design a therapeutic strategy adapted to patients' specific needs.

Outcomes of Grade Group 2 and 3 Prostate Cancer on Initial Versus Confirmatory Biopsy: Implications for Active Surveillance.

BACKGROUND: Active surveillance (AS) is recommended as the preferred treatment for men with low-risk disease. In order to optimize risk stratification and exclude undiagnosed higher-grade disease, most AS protocols recommend a confirmatory biopsy. OBJECTIVE: We aimed to compare outcomes among men with grade group (GG) 2/3 prostate cancer on initial biopsy with those among men whose disease was initially GG1 but was upgraded to GG2/3 on confirmatory biopsy. DESIGN, SETTING, AND PARTICIPANTS: We reviewed patients undergoing radical prostatectomy (RP) in two cohorts: "immediate RP group," with GG2/3 cancer on diagnostic biopsy, and "AS group," with GG1 cancer on initial biopsy that was upgraded to GG2/3 on confirmatory biopsy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Probabilities of biochemical recurrence (BCR) and salvage therapy were determined using multivariable Cox regression models with risk adjustment. Risks of adverse pathology at RP were also compared using logistic regression. RESULTS AND LIMITATIONS: The immediate RP group comprised 4009 patients and the AS group comprised 321 patients. The AS group had lower adjusted rates of adverse pathology (27% vs 35%, p = 0.003). BCR rates were lower in the AS group, although this did not reach conventional significance (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.50-1.06, p = 0.10) compared with the immediate RP group. Risk-adjusted 1- and 5-yr BCR rates were 4.6% (95% CI 3.0-6.5%) and 10.4% (95% CI 6.9-14%), respectively, for the AS group compared with 6.3% (95% CI 5.6-7.0%) and 20% (95% CI 19-22%), respectively, in the immediate RP group. A nonsignificant association was observed for salvage treatment-free survival favoring the AS group (HR 0.67, 95% CI 0.42, 1.06, p = 0.087). CONCLUSIONS: We found that men with GG1 cancer who were upgraded on confirmatory biopsy tend to have less aggressive disease than men with the same grade found at initial biopsy. These results must be confirmed in larger series before recommendations can be made regarding a more conservative approach in men with upgraded pathology on surveillance biopsy. PATIENT SUMMARY: We studied men with low-risk prostate cancer who were initially eligible for active surveillance but presented with more aggressive cancer on confirmatory biopsy. We found that outcomes for these men were better than the outcomes for those diagnosed initially with more serious cancer.

The Surgical Learning Curve for Biochemical Recurrence After Robot-assisted Radical Prostatectomy.

BACKGROUND: Improved cancer control with increasing surgical experience-the learning curve-was demonstrated for open and laparoscopic prostatectomy. In a prior single-center study, we found that this might not be the case for robot-assisted radical prostatectomy (RARP). OBJECTIVE: To investigate the relationship between prior experience of a surgeon and biochemical recurrence (BCR) after RARP. DESIGN, SETTING, AND PARTICIPANTS: We retrospectively analyzed the data of 8101 patients with prostate cancer treated with RARP by 46 surgeons at nine institutions between 2003 and 2021. Surgical experience was coded as the total number of robotic prostatectomies performed by the surgeon before the patient operation. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We evaluated the relationship of prior surgeon experience with the probability of BCR adjusting for preoperative prostate-specific antigen, pathologic stage, grade, lymph-node involvement, and year of surgery. RESULTS AND LIMITATIONS: Overall, 1047 patients had BCR. The median follow-up for patients without BCR was 33 mo (interquartile range: 14, 61). After adjusting for case mix, the relationship between surgical experience and the risk of BCR after surgery was not statistically significant (p = 0.2). The 5-yr BCR-free survival rates for a patient treated by a surgeon with prior 10, 250, and 1000 procedures performed were, respectively, 82.0%, 82.7%, and 84.8% (absolute difference between 10 and 1000 prior procedures: 1.6% [95% confidence interval: 0.4%, 3.3%). Results were robust to a number of sensitivity analyses. CONCLUSIONS: These findings suggest that, as opposed to open and laparoscopic radical prostatectomy, surgeons performing RARP achieve adequate cancer control in the early phase of their career. Further research should explore why the learning curve for robotic surgery differs from prior findings for open and laparoscopic radical prostatectomy. We hypothesize that surgical education, including simulation training and the adoption of objective performance metrics, is an important mechanism for flattening the learning curve. PATIENT SUMMARY: We investigated the relationship between biochemical recurrence after robot-assisted radical prostatectomy and surgeon's experience. Surgeons at an early stage of their career had similar outcomes to those of more experienced surgeons, and we hypothesized that surgical education in robotics might be an important determinant of such a finding.