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Objective: To investigate temporal trends in prostate cancer (PCa) radical prostatectomy (RP) candidates.
Materials and Methods: Patients who underwent RP for PCa between January 2014 and December 2019 were identified form our institutional database. Trend analysis and logistic regression models assessed RP trends after stratification of PCa patients according to D'Amico classification and Gleason score. Patients with neoadjuvant androgen deprivation or radiotherapy prior to RP were excluded from the analysis.
Results: Overall, 528 PCa patients that underwent RP were identified. Temporal trend analysis revealed a significant decrease in low-risk PCa patients from 17 to 9% (EAPC: −14.6%, p < 0.05) and GS6 PCa patients from 30 to 14% (EAPC: −17.6%, p < 0.01). This remained significant even after multivariable adjustment [low-risk PCa: (OR): 0.85, p < 0.05 and GS6 PCa: (OR): 0.79, p < 0.001]. Furthermore, a trend toward a higher proportion of intermediate-risk PCa undergoing RP was recorded.
Conclusion: Our results confirm that inverse stage migration represents an ongoing phenomenon in a contemporary RP cohort in a European tertiary care PCa center. Our results demonstrate a significant decrease in the proportion of low-risk and GS6 PCa undergoing RP and a trend toward a higher proportion of intermediate-risk PCa patients undergoing RP. This indicates a more precise patient selection when it comes to selecting suitable candidates for definite surgical treatment with RP.
Objective: We aimed to assess the correlation between serum prostate-specific antigen (PSA) and tumor burden in prostate cancer (PCa) patients undergoing radical prostatectomy (RP), because estimation of tumor burden is of high value, e.g., in men undergoing RP or with biochemical recurrence after RP. Patients and Methods: From January 2019 to June 2020, 179 consecutive PCa patients after RP with information on tumor and prostate weight were retrospectively identified from our prospective institutional RP database. Patients with preoperative systemic therapy (n=19), metastases (cM1, n=5), and locally progressed PCa (pT4 or pN1, n=50) were excluded from analyses. Histopathological features, including total weight of the prostate and specific tumor weight, were recorded by specialized uro-pathologists. Linear regression models were performed to evaluate the effect of PSA on tumor burden, measured by tumor weight after adjustment for patient and tumor characteristics. Results: Overall, median preoperative PSA was 7.0 ng/ml (interquartile range [IQR]: 5.41–10) and median age at surgery was 66 years (IQR: 61-71). Median prostate weight was 34 g (IQR: 26–46) and median tumor weight was 3.7 g (IQR: 1.8–7.1), respectively. In multivariable linear regression analysis after adjustment for patients and tumor characteristics, a significant, positive correlation could be detected between preoperative PSA and tumor weight (coefficient [coef.]: 0.37, CI: 0.15–0.6, p=0.001), indicating a robust increase in PSA of almost 0.4 ng/ml per 1g tumor weight. Conclusion: Preoperative PSA was significantly correlated with tumor weight in PCa patients undergoing RP, with an increase in PSA of almost 0.4 ng/ml per 1 g tumor weight. This might help to estimate both tumor burden before undergoing RP and in case of biochemical recurrence.
Objective: Many patients with localized prostate cancer (PCa) do not immediately undergo radical prostatectomy (RP) after biopsy confirmation. The aim of this study was to investigate the influence of “time-from-biopsy-to- prostatectomy” on adverse pathological outcomes.
Materials and Methods: Between January 2014 and December 2019, 437 patients with intermediate- and high risk PCa who underwent RP were retrospectively identified within our prospective institutional database. For the aim of our study, we focused on patients with intermediate- (n = 285) and high-risk (n = 151) PCa using D'Amico risk stratification. Endpoints were adverse pathological outcomes and proportion of nerve-sparing procedures after RP stratified by “time-from-biopsy-to-prostatectomy”: ≤3 months vs. >3 and < 6 months. Medians and interquartile ranges (IQR) were reported for continuously coded variables. The chi-square test examined the statistical significance of the differences in proportions while the Kruskal-Wallis test was used to examine differences in medians. Multivariable (ordered) logistic regressions, analyzing the impact of time between diagnosis and prostatectomy, were separately run for all relevant outcome variables (ISUP specimen, margin status, pathological stage, pathological nodal status, LVI, perineural invasion, nerve-sparing).
Results: We observed no difference between patients undergoing RP ≤3 months vs. >3 and <6 months after diagnosis for the following oncological endpoints: pT-stage, ISUP grading, probability of a positive surgical margin, probability of lymph node invasion (LNI), lymphovascular invasion (LVI), and perineural invasion (pn) in patients with intermediate- and high-risk PCa. Likewise, the rates of nerve sparing procedures were 84.3 vs. 87.4% (p = 0.778) and 61.0% vs. 78.8% (p = 0.211), for intermediate- and high-risk PCa patients undergoing surgery after ≤3 months vs. >3 and <6 months, respectively. In multivariable adjusted analyses, a time to surgery >3 months did not significantly worsen any of the outcome variables in patients with intermediate- or high-risk PCa (all p > 0.05).
Conclusion: A “time-from-biopsy-to-prostatectomy” of >3 and <6 months is neither associated with adverse pathological outcomes nor poorer chances of nerve sparing RP in intermediate- and high-risk PCa patients.
The aim of this study is to investigate the incidental prostate cancer (iPCa) detection rates of different embedding methods in a large, contemporary cohort of patients with bladder outlet obstruction (BOO) treated with transurethral surgery. We relied on an institutional tertiary-care database to identify BOO patients who underwent either transurethral loop resection or laser (Holmium:yttrium–aluminium garnet) enucleation of the prostate (HoLEP) between 01/2012 and 12/2019. Embedding methods differed with regard to the extent of the additional prostate tissue submitted following the first ten cassettes of primary embedding (cohort A: one [additional] cassette/10 g residual tissue vs. cohort B: complete embedding of the residual tissue). Detection rates of iPCa among the different embedding methods were compared. Subsequently, subgroup analyses by embedding protocol were repeated in HoLEP-treated patients only. In the overall cohort, the iPCa detection rate was 11% (46/420). In cohort A (n = 299), tissue embedding resulted in a median of 8 cassettes/patient (range 1–38) vs. a median of 15 (range 2–74) in cohort B (n = 121) (p < .001). The iPCa detection rate was 8% (23/299) and 19% (23/121) in cohort A vs. cohort B, respectively (p < .001). Virtual reduction of the number of tissue cassettes to ten cassettes resulted in a iPCa detection rate of 96% in both cohorts, missing one stage T1a/ISUP grade 1 carcinoma. Increasing the number of cassettes by two and eight cassettes, respectively, resulted in a detection rate of 100% in both cohorts without revealing high-grade carcinomas. Subgroup analyses in HoLEP patients confirmed these findings, demonstrated by a 100 vs. 96% iPCa detection rate following examination of the first ten cassettes, missing one case of T1a/ISUP 1. Examination of 8 additional cassettes resulted in a 100% detection rate. The extent of embedding of material obtained from transurethral prostate resection correlates with the iPCa detection rate. However, the submission of 10 cassettes appears to be a reasonable threshold to reduce resource utilization while maintaining secure cancer detection.
Background: To test the value of immunohistochemistry (IHC) staining in prostate biopsies for changes in biopsy results and its impact on treatment decision-making. Methods: Between January 2017–June 2020, all patients undergoing prostate biopsies were identified and evaluated regarding additional IHC staining for diagnostic purpose. Final pathologic results after radical prostatectomy (RP) were analyzed regarding the effect of IHC at biopsy. Results: Of 606 biopsies, 350 (58.7%) received additional IHC staining. Of those, prostate cancer (PCa) was found in 208 patients (59.4%); while in 142 patients (40.6%), PCa could be ruled out through IHC. IHC patients harbored significantly more often Gleason 6 in biopsy (p < 0.01) and less suspicious baseline characteristics than patients without IHC. Of 185 patients with positive IHC and PCa detection, IHC led to a change in biopsy results in 81 (43.8%) patients. Of these patients with changes in biopsy results due to IHC, 42 (51.9%) underwent RP with 59.5% harboring ≥pT3 and/or Gleason 7–10. Conclusions: Patients with IHC stains had less suspicious characteristics than patients without IHC. Moreover, in patients with positive IHC and PCa detection, a change in biopsy results was observed in >40%. Patients with changes in biopsy results partly underwent RP, in which 60% harbored significant PCa.
Background: The impact of MRI-lesion targeted (TB) and systematic biopsy (SB) Gleason score (GS) as a predictor for final pathological GS still remains unclear. Methods: All patients with TB + SB, and subsequent radical prostatectomy (RP) between 01/2014-12/2020 were analyzed. Rank correlation coefficient predicted concordance with pathological GS for patients’ TB and SB GS, as well as for the combined effect of SB + TB. Results: Of 159 eligible patients, 77% were biopsy naïve. For SB taken in addition to TB, a Spearman’s correlation of +0.33 was observed regarding final GS. Rates of concordance, upgrading, and downgrading were 37.1, 37.1 and 25.8%, respectively. For TB, a +0.52 correlation was computed regarding final GS. Rates of concordance, upgrading and downgrading for TB biopsy GS were 45.9, 33.3, and 20.8%, respectively. For the combination of SB + TB, a correlation of +0.59 was observed. Rates of concordance, upgrading and downgrading were 49.7, 15.1 and 35.2%, respectively. The combined effect of SB + TB resulted in a lower upgrading rate, relative to TB and SB (both p < 0.001), but a higher downgrading rate, relative to TB (p < 0.01). Conclusions: GS obtained from TB provided higher concordance and lower upgrading and downgrading rates, relative to SB GS with regard to final pathology. The combined effect of SB + TB led to the highest concordance rate and the lowest upgrading rate.
The objective of the study was to test the impact of implementing standard full functional-length urethral sphincter (FFLU) and neurovascular bundle preservation (NVBP) with intraoperative frozen section technique (IFT) on long-term urinary continence in patients undergoing robotic-assisted radical prostatectomy (RARP). We relied on an institutional tertiary-care database to identify patients who underwent RARP between 01/2014 and 09/2019. Until 10/2017, FFLU was not performed and decision for NVBP was taken without IFT. From 11/2017, FFLU and IFT-guided NVBP was routinely performed in all patients undergoing RARP. Long-term continence (≥ 12 months) was defined as the usage of no or one safety- pad. Uni- and multivariable logistic regression models tested the correlation between surgical approach (standard vs FFLU + NVBP) and long-term continence. Covariates consisted of age, body mass index, prostate volume and extraprostatic extension of tumor. The study cohort consisted of 142 patients, with equally sized groups for standard vs FFLU + NVBP RARP (68 vs 74 patients). Routine FFLU + NVBP implementation resulted in a long-term continence rate of 91%, compared to 63% in standard RARP (p < 0.001). Following FFLU + NVBP RARP, 5% needed 1–2, 4% 3–5 pads/24 h and no patient (0%) suffered severe long-term incontinence (> 5 pads/24 h). No significant differences in patient or tumor characteristics were recorded between both groups. In multivariable logistic regression models, FFLU + NVBP was a robust predictor for continence (Odds ratio [OR]: 7.62; 95% CI 2.51–27.36; p < 0.001). Implementation of FFLU and NVBP in patients undergoing RARP results in improved long-term continence rates of 91%.
Objectives: Within the tertiary-case database, the authors tested for differences in long-term continence rates (≥ 12 months) between prostate cancer patients with extraprostatic vs. organ-confined disease who underwent Robotic-Assisted Radical Prostatectomy (RARP).
Method: In the institutional tertiary-care database the authors identified prostate cancer patients who underwent RARP between 01/2014 and 01/2021. The cohort was divided into two groups based on tumor extension in the final RARP specimen: patients with extraprostatic (pT3/4) vs. organ-confined (pT2) disease. Additionally, the authors conducted subgroup analyses within both the extraprostatic and organ-confined disease groups to compare continence rates before and after the implementation of the new surgical technique, which included Full Functional-Length Urethra preservation (FFLU) and Neurovascular Structure-Adjacent Frozen-Section Examination (NeuroSAFE). Multivariable logistic regression models addressing long-term continence were used.
Results: Overall, the authors identified 201 study patients of whom 75 (37 %) exhibited extraprostatic and 126 (63 %) organ-confined disease. There was no significant difference in long-term continence rates between patients with extraprostatic and organ-confined disease (77 vs. 83 %; p = 0.3). Following the implementation of FFLU+ NeuroSAFE, there was an overall improvement in continence from 67 % to 89 % (Δ = 22 %; p < 0.001). No difference in the magnitude of improved continence rates between extraprostatic vs. organ-confined disease was observed (Δ = 22 % vs. Δ = 20 %). In multivariable logistic regression models, no difference between extraprostatic vs. organ-confined disease in long-term continence was observed (Odds Ratio: 0.91; p = 0.85).
Conclusion: In this tertiary-based institutional study, patients with extraprostatic and organ-confined prostate cancer exhibited comparable long-term continence rates.
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: We aimed to determine the concordance between the radiologic stage (rT), using multiparametric magnetic resonance imaging (mpMRI), and pathologic stage (pT) in patients with high-risk prostate cancer and its influence on nerve-sparing surgery compared to the use of the intraoperative frozen section technique (IFST). Methods: The concordance between rT and pT and the rates of nerve-sparing surgery and positive surgical margin were assessed for patients with high-risk prostate cancer who underwent radical prostatectomy. Results: The concordance between the rT and pT stages was shown in 66.4% (n = 77) of patients with clinical high-risk prostate cancer. The detection of patients with extraprostatic disease (≥pT3) by preoperative mpMRI showed a sensitivity, negative predictive value and accuracy of 65.1%, 51.7% and 67.5%. In addition to the suspicion of extraprostatic disease in mpMRI (≥rT3), 84.5% (n = 56) of patients with ≥rT3 underwent primary nerve-sparing surgery with IFST, resulting in 94.7% (n = 54) of men with at least unilateral nerve-sparing surgery after secondary resection with a positive surgical margin rate related to an IFST of 1.8% (n = 1). Conclusion: Patients with rT3 should not be immediately excluded from nerve-sparing surgery, as by using IFST some of these patients can safely undergo nerve-sparing surgery.