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Background: Prostate cancer is a major health concern in aging men. Paralleling an aging society, prostate cancer prevalence increases emphasizing the need for efcient diagnostic algorithms.
Methods: Retrospectively, 106 prostate tissue samples from 48 patients (mean age,
66 ± 6.6 years) were included in the study. Patients sufered from prostate cancer (n = 38) or benign prostatic hyperplasia (n = 10) and were treated with radical prostatectomy or Holmium laser enucleation of the prostate, respectively. We constructed tissue microarrays (TMAs) comprising representative malignant (n = 38) and benign (n = 68) tissue cores. TMAs were processed to histological slides, stained, digitized and assessed for the applicability of machine learning strategies and open–source tools in diagnosis of prostate cancer. We applied the software QuPath to extract features for shape, stain intensity, and texture of TMA cores for three stainings, H&E, ERG, and PIN-4. Three machine learning algorithms, neural network (NN), support vector machines (SVM), and random forest (RF), were trained and cross-validated with 100 Monte Carlo random splits into 70% training set and 30% test set. We determined AUC values for single color channels, with and without optimization of hyperparameters by exhaustive grid search. We applied recursive feature elimination to feature sets of multiple color transforms.
Results: Mean AUC was above 0.80. PIN-4 stainings yielded higher AUC than H&E and
ERG. For PIN-4 with the color transform saturation, NN, RF, and SVM revealed AUC of 0.93 ± 0.04, 0.91 ± 0.06, and 0.92 ± 0.05, respectively. Optimization of hyperparameters improved the AUC only slightly by 0.01. For H&E, feature selection resulted in no increase of AUC but to an increase of 0.02–0.06 for ERG and PIN-4.
Conclusions: Automated pipelines may be able to discriminate with high accuracy between malignant and benign tissue. We found PIN-4 staining best suited for classifcation. Further bioinformatic analysis of larger data sets would be crucial to evaluate the reliability of automated classifcation methods for clinical practice and to evaluate potential discrimination of aggressiveness of cancer to pave the way to automatic precision medicine.
Background: To examine overall survival rates within a large cohort of German prostate cancer (PCa) patients and to compare these with life-expectancy (LE) predictions derived from German life tables. We hypothesized that the advantage of good general health in radical prostatectomy (RP) patients combined with favorable cancer outcomes might lead to even higher overall survival rates over 10 years compared to the LE of a general population.
Methods: A total of 6483 patients were treated with RP between 1992 and 2007 at the Martini-Klinik Prostate Cancer Center. Preoperative risk classification was performed according to D'Amico. Postoperative risk classification was performed according to the Cancer of the Prostate Risk Assessment score (CAPRA-S). A simulated cohort was created that resembled the exact age distribution of the RP population using Monte Carlo simulation which was based on data derived from official male German life tables (1992–2017). Markov chain was used to represent natural age progression of the simulated cohort. Kaplan–Meier plots were created to display the differences between 10-year observed overall survival (OS) and the simulated, predicted LE.
Results: For D'Amico low risk and intermediate risk, 10-year OS was 12.0% and 9.2% above predicted LE in the simulated cohort, respectively. For D'Amico high risk, OS was virtually the same as predicted LE (0.8% difference in favor of RP treated patients). For CAPRA-S low and intermediate risk, OS was 11.8% and 9.7% above predicted LE. For CAPRA-S high risk, OS was virtually the same as predicted LE (0.3% difference in favor of the simulated cohort).
Conclusions: Low- and intermediate risk PCa patients treated with RP can expect a very favorable overall survival, that even exceeds LE predictions. High risk patients' overall survival perfectly aligns with LE predictions.
Objectives: To test the effect of race/ethnicity on cancer-specific mortality after radical prostatectomy or external beam radiotherapy in localized prostate cancer patients. Methods: In the Surveillance, Epidemiology and End Results database 2004–2016, we identified intermediate-risk and high-risk white (n = 151 632), Asian (n = 11 189), Hispanic/Latino (n = 20 077) and African American (n = 32 550) localized prostate cancer patients, treated with external beam radiotherapy or radical prostatectomy. Race/ethnicity-stratified cancer-specific mortality analyses relied on competing risks regression, after propensity score matching for patient and cancer characteristics. Results: Compared with white patients, Asian intermediate- and high-risk external beam radiotherapy patients showed lower cancer-specific mortality (hazard ratio 0.58 and 0.70, respectively, both P ≤ 0.02). Additionally, Asian high-risk radical prostatectomy patients also showed lower cancer-specific mortality than white patients (hazard ratio 0.72, P = 0.04), but not Asian intermediate-risk radical prostatectomy patients (P = 0.08). Conversely, compared with white patients, African American intermediate-risk radical prostatectomy patients showed higher cancer-specific mortality (hazard ratio 1.36, P = 0.01), but not African American high-risk radical prostatectomy or intermediate- and high-risk external beam radiotherapy patients (all P ≥ 0.2). Finally, compared with white people, no cancer-specific mortality differences were recorded for Hispanic/Latino patients after external beam radiotherapy or radical prostatectomy, in both risk levels (P ≥ 0.2). Conclusions: Relative to white patients, an important cancer-specific mortality advantage applies to intermediate-risk and high-risk Asian prostate cancer patients treated with external beam radiotherapy, and to high-risk Asian patients treated with radical prostatectomy. These observations should be considered in pretreatment risk stratification and decision-making.
Objectives: To test the effect of race/ethnicity on cancer-specific mortality after radical prostatectomy or external beam radiotherapy in localized prostate cancer patients. Methods: In the Surveillance, Epidemiology and End Results database 2004–2016, we identified intermediate-risk and high-risk white (n = 151 632), Asian (n = 11 189), Hispanic/Latino (n = 20 077) and African American (n = 32 550) localized prostate cancer patients, treated with external beam radiotherapy or radical prostatectomy. Race/ethnicity-stratified cancer-specific mortality analyses relied on competing risks regression, after propensity score matching for patient and cancer characteristics. Results: Compared with white patients, Asian intermediate- and high-risk external beam radiotherapy patients showed lower cancer-specific mortality (hazard ratio 0.58 and 0.70, respectively, both P ≤ 0.02). Additionally, Asian high-risk radical prostatectomy patients also showed lower cancer-specific mortality than white patients (hazard ratio 0.72, P = 0.04), but not Asian intermediate-risk radical prostatectomy patients (P = 0.08). Conversely, compared with white patients, African American intermediate-risk radical prostatectomy patients showed higher cancer-specific mortality (hazard ratio 1.36, P = 0.01), but not African American high-risk radical prostatectomy or intermediate- and high-risk external beam radiotherapy patients (all P ≥ 0.2). Finally, compared with white people, no cancer-specific mortality differences were recorded for Hispanic/Latino patients after external beam radiotherapy or radical prostatectomy, in both risk levels (P ≥ 0.2). Conclusions: Relative to white patients, an important cancer-specific mortality advantage applies to intermediate-risk and high-risk Asian prostate cancer patients treated with external beam radiotherapy, and to high-risk Asian patients treated with radical prostatectomy. These observations should be considered in pretreatment risk stratification and decision-making.
Background: A trend towards inverse stage migration in prostate cancer (PCa) was reported. However, previous analyses did not take into account potential differences in sampling strategies (number of biopsy cores), which might have confounded these reports.
Material and Methods: Within our single-institutional database we identified PCa patients treated with radical prostatectomy (RP) between 2000 and 2020 (n = 21,646). We calculated the estimated annual percentage change (EAPC) for D'Amico risk groups, biopsy Gleason Grade Group (GGG), PSA and cT stage as well as postoperative RP GGG and pT stage relying on log linear regression methodology. Subsequently, we repeated the analyses after adjustment for number of cores obtained at biopsy.
Results: Absolute rates of D'Amico low risk decreased (−30.1%), while intermediate and high risk increased (+21.2% and +9.0%, respectively). Rates of GGG I decreased (−50.0%), while GGG II–V increased, with the largest increase in GGG II (+22.5%). This trend, albeit less pronounced, was also recorded after adjusted EAPC analyses (p < .05). Specifically, EAPC values for D'Amico low vs intermediate vs high risk were −1.07%, +0.37%, +0.45%, respectively, and EAPC values for GGG ranged between −0.71% (GGG I) and +0.80% (GGG IV). Finally, an increase in ≥cT2 (EAPC: +3.16%) was displayed (all p < .001). These trends were confirmed in EAPC calculations in RP GGG and pT stages (p < .001).
Conclusion: Our findings confirm the trend towards less frequent treatment of low risk PCa and more frequent treatment of high risk PCa, also after adjustment for number of biopsy cores.
Purpose: To test the value of preoperative and postoperative cystatin C (CysC) as a predictor on kidney function after partial (PN) or radical nephrectomy (RN) in renal cell carcinoma (RCC) patients with normal preoperative renal function.
Methods: From 01/2011 to 12/2014, 195 consecutive RCC patients with a preoperative estimated glomerular filtration rate (eGFR) > 60 ml/min/1.73m2 underwent surgical RCC treatment with either PN or RN. Logistic and linear regression models tested for the effect of CysC as a predictor of new-onset chronic kidney disease in follow-up (eGFR < 60 ml/min/1.73m2). Moreover, postoperative CysC and creatinine values were compared for kidney function estimation.
Results: Of 195 patients, 129 (66.2%) underwent PN. In postoperative and in follow-up setting (median 14 months, IQR 10–20), rates of eGFR < 60 ml/min/1.73m2 were 55.9 and 30.2%. In multivariable logistic regression models, preoperative CysC [odds ratio (OR): 18.3] and RN (OR: 13.5) were independent predictors for a reduced eGFR < 60 ml/min/1.73m2 in follow-up (both p < 0.01), while creatinine was not. In multivariable linear regression models, a difference of the preoperative CysC level of 0.1 mg/dl estimated an eGFR decline in follow-up of about 5.8 ml/min/1.73m2. Finally, we observed a plateau of postoperative creatinine values in the range of 1.2–1.3 mg/dl, when graphically depicted vs. postoperative CysC values (‘creatinine blind area’).
Conclusion: Preoperative CysC predicts renal function impairment following RCC surgery. Furthermore, CysC might be superior to creatinine for renal function monitoring in the early postoperative setting.
Background: We hypothesized that lymph node dissection (LND) at salvage radical prostatectomy may be associated with lower cancer-specific mortality (CSM) and we tested this hypothesis.
Methods: We relied on surveillance, epidemiology, and end results (2004–2016) to identify all salvage radical prostatectomy patients. Categorical, as well as univariate and multivariate Cox regression models tested the effect of LND (LND performed vs. not), as well as at its extent (log-transformed lymph node count) on CSM.
Results: Of 427 salvage radical prostatectomy patients, 120 (28.1%) underwent LND with a median lymph node count of 6 (interquartile range [IQR], 3–11). According to LND status, no significant or clinically meaningful differences were recorded in PSA at diagnosis, stage and biopsy Gleason score at diagnosis, except for age at prostate cancer diagnosis (LND performed 63 vs. 68 years LND not performed, p < .001). LND status (performed) was an independent predictor of lower CSM (hazard ratio [HR] 0.47; p = .03). Similarly, lymph node count (log transformed) also independently predicted lower CSM (HR: 0.60; p = .01). After the 7th removed lymph node, the effect of CSM became marginal. The effect of N-stage on CSM could not be tested due to insufficient number of observations.
Conclusions: Salvage radical prostatectomy is rarely performed and LND at salvage radical prostatectomy is performed in a minority of patients. However, LND at salvage radical prostatectomy is associated with lower CSM. Moreover, LND extent also exerts a protective effect on CSM. These observations should be considered in salvage radical prostatectomy candidates.
Background: To test the effect of urological primary cancers (bladder, kidney, testis, upper tract, penile, urethral) on overall mortality (OM) after secondary prostate cancer (PCa). Methods: Within the Surveillance, Epidemiology and End Results (SEER) database, patients with urological primary cancers and concomitant secondary PCa (diagnosed 2004-2016) were identified and were matched in 1:4 fashion with primary PCa controls. OM was compared between secondary and primary PCa patients and stratified according to primary urological cancer type, as well as to time interval between primary urological cancer versus secondary PCa diagnoses. Results: We identified 5,987 patients with primary urological and secondary PCa (bladder, n = 3,287; kidney, n = 2,127; testis, n = 391; upper tract, n = 125; penile, n = 47; urethral, n = 10) versus 531,732 primary PCa patients. Except for small proportions of Gleason grade group and age at diagnosis, PCa characteristics between secondary and primary PCa were comparable. Conversely, proportions of secondary PCa patients which received radical prostatectomy were smaller (29.0 vs. 33.5%), while no local treatment rates were higher (34.2 vs. 26.3%). After 1:4 matching, secondary PCa patients exhibited worse OM than primary PCa patients, except for primary testis cancer. Here, no OM differences were recorded. Finally, subgroup analyses showed that the survival disadvantage of secondary PCa patients decreased with longer time interval since primary cancer diagnosis. Conclusions: After detailed matching for PCa characteristics, secondary PCa patients exhibit worse survival, except for testis cancer patients. The survival disadvantage is attenuated, when secondary PCa diagnosis is made after longer time interval, since primary urological cancer diagnosis.
Background: To test the effect of urological primary cancers (bladder, kidney, testis, upper tract, penile, urethral) on overall mortality (OM) after secondary prostate cancer (PCa). Methods: Within the Surveillance, Epidemiology and End Results (SEER) database, patients with urological primary cancers and concomitant secondary PCa (diagnosed 2004-2016) were identified and were matched in 1:4 fashion with primary PCa controls. OM was compared between secondary and primary PCa patients and stratified according to primary urological cancer type, as well as to time interval between primary urological cancer versus secondary PCa diagnoses. Results: We identified 5,987 patients with primary urological and secondary PCa (bladder, n = 3,287; kidney, n = 2,127; testis, n = 391; upper tract, n = 125; penile, n = 47; urethral, n = 10) versus 531,732 primary PCa patients. Except for small proportions of Gleason grade group and age at diagnosis, PCa characteristics between secondary and primary PCa were comparable. Conversely, proportions of secondary PCa patients which received radical prostatectomy were smaller (29.0 vs. 33.5%), while no local treatment rates were higher (34.2 vs. 26.3%). After 1:4 matching, secondary PCa patients exhibited worse OM than primary PCa patients, except for primary testis cancer. Here, no OM differences were recorded. Finally, subgroup analyses showed that the survival disadvantage of secondary PCa patients decreased with longer time interval since primary cancer diagnosis. Conclusions: After detailed matching for PCa characteristics, secondary PCa patients exhibit worse survival, except for testis cancer patients. The survival disadvantage is attenuated, when secondary PCa diagnosis is made after longer time interval, since primary urological cancer diagnosis.
The effect of race/ethnicity on cancer-specific mortality after salvage radical prostatectomy
(2022)
Background: To test the effect of race/ethnicity on cancer-specific mortality (CSM) after salvage radical prostatectomy (SRP).
Material and methods: We relied on the Surveillance, Epidemiology and End Results database (SEER, 2004–2016) to identify SRP patients of all race/ethnicity background. Univariate and multivariate Cox regression models addressed CSM according to race/ethnicity.
Results: Of 426 assessable SRP patients, Caucasians accounted for 299 (69.9%) vs. 68 (15.9%) African-Americans vs. 39 (9.1%) Hispanics vs. 20 (4.7%) Asians. At diagnosis, African-Americans (64 years) were younger than Caucasians (66 years), but not younger than Hispanics (66 years) and Asians (67 years). PSA at diagnosis was significantly higher in African-Americans (13.2 ng/ml), Hispanics (13.0 ng/ml), and Asians (12.2 ng/ml) than in Caucasians (7.8 ng/ml, p = 0.01). Moreover, the distribution of African-Americans (10.3%–36.6%) and Hispanics (0%–15.8%) varied according to SEER region. The 10-year CSM was 46.5% in African-Americans vs. 22.4% in Caucasians vs. 15.4% in Hispanics vs. 15.0% in Asians. After multivariate adjustment (for age, clinical T stage, lymph node dissection status), African-American race/ethnicity was an independent predictor of higher CSM (HR: 2.2, p < 0.01), but not Hispanic or Asian race/ethnicity. The independent effect of African-American race/ethnicity did not persist after further adjustment for PSA.
Conclusion: African-Americans treated with SRP are at higher risk of CSM than other racial/ethnic groups and also exhibited the highest baseline PSA. The independent effect of African-American race/ethnicity on higher CSM no longer applies after PSA adjustment since higher PSA represents a distinguishing feature in African-American patients.