Predictors of major complications and the association with oncological outcomes after radical cystectomy for bladder cancer:A nationwide registry study

Introduction:Radical cystectomy improves survival of patients with muscle invasive and high-risk non-muscle invasive bladder cancer, but is a challenging surgical procedure as patients may experience major complications after surgery.Objectives:To assess the incidence of Clavien-Dindo ≥3 complications in patients who underwent radical cystectomy and to assess the association of these complications with pre-operative and peroperative parameters. The secondary aim was to study the association of complications with long-term oncological outcome.Methods:A nationwide registry was set up in 19 Dutch hospitals that studied patients with muscle invasive bladder cancer and high-risk non-muscle invasive bladder cancer treated by radical cystectomy. Major complications were classified as complications that were related to uretero-ileal anastomosis, intra-abdominal (e.g. urinoma, bowel leakage) infectious and cardiovascular complications. Multivariable logistic regression analyses were performed to assess the correlation between these groups and perioperative, clinical and pathological factors. Kaplan-Meier survival curves were constructed to analyze the correlation between complications and overall survival.Results:The study population consisted of 1,464 patients, of whom 420 (29%) developed severe complications. The most common complications were intra-abdominal (n=328, 60%) and uretero-ileal anastomosis related (n=92, 17%). Male gender (odds ratio 1.6, p=0.007), American Society of Anaesthesiologists score ≥3 (odds ratio 1.6, p=0.003), Charlson Comorbidity Index score ≥5 (odds ratio 2.1, p=0.002) and blood loss >700ml (odds ratio 1.4, p=0.044) were associated with severe complications. In addition, open radical cystectomy was associated with multiple complications (odds ratio 2.6, p=0.001). Furthermore, the overall survival of patients with major complications was worse than those who had no major complications. The median overall survival was 3.8 years versus 6.2 years for patients with and without severe complications (p<0.001).Conclusions:In a real-world setting, 29% of patients undergoing radical cystectomy developed severe complications. The risk of severe complications was higher in men, patients with impaired pre-operative condition, and in those who underwent open surgery. Severe complications had a negative impact on overall survival

The accuracy and intra- and interobserver variability of PSMA PET/CT for the local staging of primary prostate cancer

PURPOSE: Prostate-specific membrane antigen (PSMA) positron emission tomography/ computed tomography (PET/CT) is recognized as the most accurate imaging modality for detection of metastatic high-risk prostate cancer (PCa). Its role in the local staging of disease is yet unclear. We assessed the intra- and interobserver variability, as well as the diagnostic accuracy of the PSMA PET/CT based molecular imaging local tumour stage (miT-stage) for the local tumour stage assessment in a large, multicentre cohort of patients with intermediate and high-risk primary PCa, with the radical prostatectomy specimen (pT-stage) serving as the reference standard.METHODS: A total of 600 patients who underwent staging PSMA PET/CT before robot-assisted radical prostatectomy was studied. In 579 PSMA positive primary prostate tumours a comparison was made between miT-stage as assessed by four nuclear physicians and the pT-stage according to ISUP protocol. Sensitivity, specificity and diagnostic accuracy were determined. In a representative subset of 100 patients, the intra-and interobserver variability were assessed using Kappa-estimates.RESULTS: The sensitivity and specificity of the PSMA PET/CT based miT-stage were 58% and 59% for pT3a-stage, 30% and 97% for ≥ pT3b-stage, and 68% and 61% for overall ≥ pT3-stage, respectively. No statistically significant differences in diagnostic accuracy were found between tracers. We found a substantial intra-observer agreement for PSMA PET/CT assessment of ≥ T3-stage (k 0.70) and ≥ T3b-stage (k 0.75), whereas the interobserver agreement for the assessment of ≥ T3-stage (k 0.47) and ≥ T3b-stage (k 0.41) were moderate.CONCLUSION: In a large, multicentre study evaluating 600 patients with newly diagnosed intermediate and high-risk PCa, we showed that PSMA PET/CT may have a value in local tumour staging when pathological tumour stage in the radical prostatectomy specimen was used as the reference standard. The intra-observer and interobserver variability of assessment of tumour extent on PSMA PET/CT was moderate to substantial.</p

The accuracy and intra- and interobserver variability of PSMA PET/CT for the local staging of primary prostate cancer

PURPOSE: Prostate-specific membrane antigen (PSMA) positron emission tomography/ computed tomography (PET/CT) is recognized as the most accurate imaging modality for detection of metastatic high-risk prostate cancer (PCa). Its role in the local staging of disease is yet unclear. We assessed the intra- and interobserver variability, as well as the diagnostic accuracy of the PSMA PET/CT based molecular imaging local tumour stage (miT-stage) for the local tumour stage assessment in a large, multicentre cohort of patients with intermediate and high-risk primary PCa, with the radical prostatectomy specimen (pT-stage) serving as the reference standard.METHODS: A total of 600 patients who underwent staging PSMA PET/CT before robot-assisted radical prostatectomy was studied. In 579 PSMA positive primary prostate tumours a comparison was made between miT-stage as assessed by four nuclear physicians and the pT-stage according to ISUP protocol. Sensitivity, specificity and diagnostic accuracy were determined. In a representative subset of 100 patients, the intra-and interobserver variability were assessed using Kappa-estimates.RESULTS: The sensitivity and specificity of the PSMA PET/CT based miT-stage were 58% and 59% for pT3a-stage, 30% and 97% for ≥ pT3b-stage, and 68% and 61% for overall ≥ pT3-stage, respectively. No statistically significant differences in diagnostic accuracy were found between tracers. We found a substantial intra-observer agreement for PSMA PET/CT assessment of ≥ T3-stage (k 0.70) and ≥ T3b-stage (k 0.75), whereas the interobserver agreement for the assessment of ≥ T3-stage (k 0.47) and ≥ T3b-stage (k 0.41) were moderate.CONCLUSION: In a large, multicentre study evaluating 600 patients with newly diagnosed intermediate and high-risk PCa, we showed that PSMA PET/CT may have a value in local tumour staging when pathological tumour stage in the radical prostatectomy specimen was used as the reference standard. The intra-observer and interobserver variability of assessment of tumour extent on PSMA PET/CT was moderate to substantial.</p

Development and Internal Validation of a Novel Nomogram Predicting the Outcome of Salvage Radiation Therapy for Biochemical Recurrence after Radical Prostatectomy in Patients without Metastases on Restaging Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography

BACKGROUND AND OBJECTIVE: Owing to the greater use of prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) in patients with biochemical recurrence (BCR) of prostate cancer (PCa) after robot-assisted radical prostatectomy (RARP), patient selection for local salvage radiation therapy (sRT) has changed. Our objective was to determine the short-term efficacy of sRT in patients with BCR after RARP, and to develop a novel nomogram predicting BCR-free survival after sRT in a nationwide contemporary cohort of patients who underwent PSMA PET/CT before sRT for BCR of PCa, without evidence of metastatic disease.METHODS: All 302 eligible patients undergoing PCa sRT in four reference centers between September 2015 and August 2020 were included. We conducted multivariable logistic regression analysis using a backward elimination procedure to develop a nomogram for predicting biochemical progression of PCa, defined as prostate-specific antigen (PSA) ≥0.2 ng/ml above the post-sRT nadir within 1 yr after sRT.KEY FINDINGS AND LIMITATIONS: Biochemical progression of disease within 1 yr after sRT was observed for 56/302 (19%) of the study patients. The final predictive model included PSA at sRT initiation, pathological grade group, surgical margin status, PSA doubling time, presence of local recurrence on PSMA PET/CT, and the presence of biochemical persistence (first PSA result ≥0.1 ng/ml) after RARP. The area under the receiver operating characteristic curve for this model was 0.72 (95% confidence interval 0.64-0.79). Using our nomogram, patients with a predicted risk of &gt;20% had a 30.8% chance of developing biochemical progression within 1 yr after sRT.CONCLUSIONS: Our novel nomogram may facilitate better patient counseling regarding early oncological outcome after sRT. Patients with high risk of biochemical progression may be candidates for more extensive treatment.PATIENT SUMMARY: We developed a new tool for predicting cancer control outcomes of radiotherapy for patients with recurrence of prostate cancer after surgical removal of their prostate. This tool may help in better counseling of these patients with recurrent cancer regarding their early expected outcome after radiotherapy.</p

Development and Internal Validation of a Novel Nomogram Predicting the Outcome of Salvage Radiation Therapy for Biochemical Recurrence after Radical Prostatectomy in Patients without Metastases on Restaging Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography

BACKGROUND AND OBJECTIVE: Owing to the greater use of prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) in patients with biochemical recurrence (BCR) of prostate cancer (PCa) after robot-assisted radical prostatectomy (RARP), patient selection for local salvage radiation therapy (sRT) has changed. Our objective was to determine the short-term efficacy of sRT in patients with BCR after RARP, and to develop a novel nomogram predicting BCR-free survival after sRT in a nationwide contemporary cohort of patients who underwent PSMA PET/CT before sRT for BCR of PCa, without evidence of metastatic disease.METHODS: All 302 eligible patients undergoing PCa sRT in four reference centers between September 2015 and August 2020 were included. We conducted multivariable logistic regression analysis using a backward elimination procedure to develop a nomogram for predicting biochemical progression of PCa, defined as prostate-specific antigen (PSA) ≥0.2 ng/ml above the post-sRT nadir within 1 yr after sRT.KEY FINDINGS AND LIMITATIONS: Biochemical progression of disease within 1 yr after sRT was observed for 56/302 (19%) of the study patients. The final predictive model included PSA at sRT initiation, pathological grade group, surgical margin status, PSA doubling time, presence of local recurrence on PSMA PET/CT, and the presence of biochemical persistence (first PSA result ≥0.1 ng/ml) after RARP. The area under the receiver operating characteristic curve for this model was 0.72 (95% confidence interval 0.64-0.79). Using our nomogram, patients with a predicted risk of &gt;20% had a 30.8% chance of developing biochemical progression within 1 yr after sRT.CONCLUSIONS: Our novel nomogram may facilitate better patient counseling regarding early oncological outcome after sRT. Patients with high risk of biochemical progression may be candidates for more extensive treatment.PATIENT SUMMARY: We developed a new tool for predicting cancer control outcomes of radiotherapy for patients with recurrence of prostate cancer after surgical removal of their prostate. This tool may help in better counseling of these patients with recurrent cancer regarding their early expected outcome after radiotherapy.</p

Predictors of major complications and the association with oncological outcomes after radical cystectomy for bladder cancer:A nationwide registry study

Introduction:Radical cystectomy improves survival of patients with muscle invasive and high-risk non-muscle invasive bladder cancer, but is a challenging surgical procedure as patients may experience major complications after surgery.Objectives:To assess the incidence of Clavien-Dindo ≥3 complications in patients who underwent radical cystectomy and to assess the association of these complications with pre-operative and peroperative parameters. The secondary aim was to study the association of complications with long-term oncological outcome.Methods:A nationwide registry was set up in 19 Dutch hospitals that studied patients with muscle invasive bladder cancer and high-risk non-muscle invasive bladder cancer treated by radical cystectomy. Major complications were classified as complications that were related to uretero-ileal anastomosis, intra-abdominal (e.g. urinoma, bowel leakage) infectious and cardiovascular complications. Multivariable logistic regression analyses were performed to assess the correlation between these groups and perioperative, clinical and pathological factors. Kaplan-Meier survival curves were constructed to analyze the correlation between complications and overall survival.Results:The study population consisted of 1,464 patients, of whom 420 (29%) developed severe complications. The most common complications were intra-abdominal (n=328, 60%) and uretero-ileal anastomosis related (n=92, 17%). Male gender (odds ratio 1.6, p=0.007), American Society of Anaesthesiologists score ≥3 (odds ratio 1.6, p=0.003), Charlson Comorbidity Index score ≥5 (odds ratio 2.1, p=0.002) and blood loss &gt;700ml (odds ratio 1.4, p=0.044) were associated with severe complications. In addition, open radical cystectomy was associated with multiple complications (odds ratio 2.6, p=0.001). Furthermore, the overall survival of patients with major complications was worse than those who had no major complications. The median overall survival was 3.8 years versus 6.2 years for patients with and without severe complications (p&lt;0.001).Conclusions:In a real-world setting, 29% of patients undergoing radical cystectomy developed severe complications. The risk of severe complications was higher in men, patients with impaired pre-operative condition, and in those who underwent open surgery. Severe complications had a negative impact on overall survival

Prostate cancer development is not affected by statin use in patients with elevated psa levels

Background: The role of statins in prostate cancer (PCa) remains unclear. Conflicting evidence has been found concerning risk reduction with the use of statins on biochemical recurrence (BCR). In this study, we evaluated whether statin use decreases the incidence of advanced PCa in males with elevated prostate-specific antigen (PSA; ≥4.0 ng/mL) levels and determined whether statin use reduces the risk of BCR after radical prostatectomy (RP). Methods: Patients visiting the outpatient urology clinic of the VU Medical Center between 2006 and 2018 with elevated PSA were retrospectively analyzed. Biochemical recurrence after RP was defined as a PSA level of ≥0.2 ng/mL (measured twice). Results: A total of 1566 patients were included, of which 1122 (72%) were diagnosed with PCa. At the time of diagnosis, 252 patients (23%) used statins compared to 83 patients (19%) in the non-malignancy group (p = 0.10). No differences were found in the use of statins between the different risk groups. No correlation was found between the risk of BCR after RP and the use of statins in the total (p = 0.20), the intermediate-risk group (p = 0.63) or the high-risk group (p = 0.14). Conclusion: The use of statins does not affect PCa development/progression in patients with elevated PSA levels, nor the development of BCR after RP

Nuclear imaging for bone metastases in prostate cancer: The Emergence of Modern Techniques Using Novel Radiotracers

Accurate staging of prostate cancer (PCa) at initial diagnosis and at biochemical recurrence is important to determine prognosis and the optimal treatment strategy. To date, treatment of metastatic PCa has mostly been based on the results of conventional imaging with abdominopelvic computed tomography (CT) and bone scintigraphy. However, these investigations have limited sensitivity and specificity which impairs their ability to accurately identify and quantify the true extent of active disease. Modern imaging modalities, such as those based on the detection of radioactively labeled tracers with combined positron emission tomography/computed tomography (PET/CT) scanning have been developed specifically for the detection of PCa. Novel radiotracers include18F-sodium fluoride (NaF),11C-/18F-fluorocholine (FCH),18F-fluordihydrotestosterone (FDHT),68Gallium and18F-radiolabeled prostate-specific membrane antigen (e.g.,68Ga-PSMA-11,18F-DCFPyL). PET/CT with these tracers outperforms conventional imaging. As a result of this, although their impact on outcome needs to be better defined in appropriate clinical trials, techniques like prostate-specific membrane antigen (PSMA) PET/CT have been rapidly adopted into clinical practice for (re)staging PCa. This review focuses on nuclear imaging for PCa bone metastases, summarizing the literature on conventional imaging (focusing on CT and bone scintigraphy—magnetic resonance imaging is not addressed in this review), highlighting the prognostic importance of high and low volume metastatic disease which serves as a driver for the development of better imaging techniques, and finally discussing modern nuclear imaging with novel radiotracers