Abstract Context Pelvic lymph node dissection (PLND) in prostate cancer is the most effective method for detecting lymph node metastases. However, a decline in the rate of PLND during radical ...prostatectomy (RP) has been noted. This is likely the result of prostate cancer stage migration in the prostate-specific antigen-screening era, and the introduction of minimally invasive approaches such as robot-assisted radical prostatectomy (RARP). Objective To assess the efficacy, limitations, and complications of PLND during RARP. Evidence acquisition A review of the literature was performed using the Medline, Scopus, and Web of Science databases with no restriction of language from January 1990 to December 2012. The literature search used the following terms: prostate cancer, radical prostatectomy, robot-assisted , and lymph node dissection. Evidence synthesis The median value of nodal yield at PLND during RARP ranged from 3 to 24 nodes. As seen in open and laparoscopic RP series, the lymph node positivity rate increased with the extent of dissection during RARP. Overall, PLND-only related complications are rare. The most frequent complication after PLND is symptomatic pelvic lymphocele, with occurrence ranging from 0% to 8% of cases. The rate of PLND-associated grade 3–4 complications ranged from 0% to 5%. PLND is associated with increased operative time. Available data suggest equivalence of PLND between RARP and other surgical approaches in terms of nodal yield, node positivity, and intraoperative and postoperative complications. Conclusions PLND during RARP can be performed effectively and safely. The overall number of nodes removed, the likelihood of node positivity, and the types and rates of complications of PLND are similar to pure laparoscopic and open retropubic procedures.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract Background Gleason grading is the strongest prognostic parameter in prostate cancer. Gleason grading is categorized as Gleason ≤6, 3 + 4, 4 + 3, 8, and 9–10, but there is variability within ...these subgroups. For example, Gleason 4 components may range from 5–45% in a Gleason 3 + 4 = 7 cancer. Objective To assess the clinical relevance of the fractions of Gleason patterns. Design, setting, and participants Prostatectomy specimens from 12 823 consecutive patients and of 2971 matched preoperative biopsies for which clinical data with an annual follow-up between 2005 and 2014 were available from the Martini-Klinik database. Outcome measurements and statistical analysis To evaluate the utility of quantitative grading, the fraction of Gleason 3, 4, and 5 patterns seen in biopsies and prostatectomies were recorded. Gleason grade fractions were compared with prostatectomy findings and prostate-specific antigen recurrence. Results and limitations Our data suggest a striking utility of quantitative Gleason grading. In prostatectomy specimens, there was a continuous increase of the risk of prostate-specific antigen recurrence with increasing percentage of Gleason 4 fractions with remarkably small differences in outcome at clinically important thresholds (0% vs 5%; 40% vs 60% Gleason 4), distinguishing traditionally established prognostic groups. Also, in biopsies, the quantitative Gleason scoring identified various intermediate risk groups with respect to Gleason findings in corresponding prostatectomies. Quantitative grading may also reduce the clinical impact of interobserver variability because borderline findings such as tumors with 5%, 40%, or 60% Gleason 4 fractions and very small Gleason 5 fractions (with pivotal impact on the Gleason score) are disclaimed. Conclusions Quantitative Gleason pattern data should routinely be provided in addition to Gleason score categories, both in biopsies and in prostatectomy specimens. Patient summary Gleason score is the most important prognostic parameter in prostate cancer, but prone to interobserver variation. The results of our study show that morphological aspects that define the Gleason grade in prostate cancer represent a continuum. Quantitation of Gleason patterns provides clinically relevant information beyond the traditional Gleason grading categories ≤3 + 3, 3 + 4, 4 + 3, 8, 9–10. Quantitative Gleason scoring can help to minimize variations between different pathologists and substantially aid in optimized therapy decision-making.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Abstract Background A key prerequisite for urinary continence after radical prostatectomy (RP) is the functional length of the urethral sphincter and the stabilisation of its anatomic position within ...the pelvic floor. Objective We describe our modified surgical technique for full functional-length urethra (FFLU) preservation during RP. Design, setting, and participants We analysed 691 consecutive patients who underwent RP over a 12-mo period (285 without and 406 with the FFLU technique). Surgical procedure The full functional urethra length was preserved by performing an individualised apical preparation strictly along anatomic landmarks, respecting the individual length of the intraprostatically located proportion of the urethral sphincter. Anatomic fixation of the sphincter was reached by a thorough preservation of the pelvic floor and anatomic restoration of the Mueller's ligaments. Measurements Continence rates were assessed at 7 d and 12 mo after removal of the catheter. Continence was defined as the use of no pads and no urinary leakage. Results and limitations The continence rates were 50.1% and 30.9% 1 wk after catheter removal ( p < 0.0001) and 96.9% and 94.7% ( p = 0.59) at 12 mo after surgery in patients operated on with the FFLU technique versus the non-FFLU technique. In multivariate regression analysis, only the surgical technique correlated significantly with the continence status 1 wk after catheter removal. Neither the overall positive surgical margin rates nor the number of positive margins at the urethral resection border differed significantly between the FFLU and non-FFLU groups (13.6% and 0.5% vs 14.9% and 1.3%, respectively). Although the patients’ baseline characteristics were similar in the two surgical groups, the patients were not preoperatively randomised, and the number of patients in the groups was asymmetric. Conclusions The combination of an FFLU preparation and improved preservation of the anatomic fixation of the urethral sphincter complex resulted in significantly increased early urinary continence results.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract Background Strategies to reduce prostate-specific antigen (PSA)–driven prostate cancer (PCa) overdiagnosis and overtreatment seem to be necessary. Objective To test the accuracy of serum ...isoform −2proPSA (p2PSA) and its derivatives, percentage of p2PSA to free PSA (fPSA; %p2PSA) and the Prostate Health Index (PHI)—called index tests —in discriminating between patients with and without PCa. Design, setting, and participants This was an observational, prospective cohort study of patients from five European urologic centers with a total PSA (tPSA) range of 2–10 ng/ml who were subjected to initial prostate biopsy for suspected PCa. Outcome measurements and statistical analysis The primary end point was to evaluate the specificity, sensitivity, and diagnostic accuracy of index tests in determining the presence of PCa at prostate biopsy in comparison to tPSA, fPSA, and percentage of fPSA to tPSA (%fPSA) (standard tests) and the number of prostate biopsies that could be spared using these tests. Multivariable logistic regression models were complemented by predictive accuracy analysis and decision curve analysis. Results and limitations Of >646 patients, PCa was diagnosed in 264 (40.1%). Median tPSA (5.7 vs 5.8 ng/ml; p = 0.942) and p2PSA (15.0 vs 14.7 pg/ml) did not differ between groups; conversely, median fPSA (0.7 vs 1 ng/ml; p < 0.001), %fPSA (0.14 vs 0.17; p < 0.001), %p2PSA (2.1 vs 1.6; p < 0.001), and PHI (48.2 vs 38; p < 0.001) did differ significantly between men with and without PCa. In multivariable logistic regression models, p2PSA, %p2PSA, and PHI significantly increased the accuracy of the base multivariable model by 6.4%, 5.6%, and 6.4%, respectively (all p < 0.001). At a PHI cut-off of 27.6, a total of 100 (15.5%) biopsies could have been avoided. The main limitation is that cases were selected on the basis of their initial tPSA values. Conclusions In patients with a tPSA range of 2–10 ng/ml, %p2PSA and PHI are the strongest predictors of PCa at initial biopsy and are significantly more accurate than tPSA and %fPSA. Trial registration The study is registered at http://www.controlled-trials.com , ref. ISRCTN04707454.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Purpose We evaluated the clinical utility of the PCA3 assay in guiding initial biopsy decisions in prostate cancer. Materials and Methods A European, prospective, multicenter study enrolled men with ...a serum total prostate specific antigen of 2.5 to 10 ng/ml scheduled for initial biopsy. After digital rectal examination first catch urine was collected. PCA3 scores were determined using the PROGENSA® PCA3 assay and compared to biopsy outcome. The diagnostic accuracy of PCA3 was compared to total prostate specific antigen, prostate specific antigen density and %free prostate specific antigen. Results In 516 men the positive biopsy rate was 40%. An increasing PCA3 score corresponded with an increasing probability of a positive biopsy. The mean PCA3 score was higher in men with a positive vs a negative biopsy (69.6 vs 31.0, median 50 vs 18, p <0.0001). The PCA3 score was independent of age, total prostate specific antigen and prostate volume. The PCA3 score (cutoff of 35) had a sensitivity of 64% and specificity of 76%. ROC analysis showed a significantly higher AUC for the PCA3 score vs total prostate specific antigen, prostate specific antigen density and %free prostate specific antigen. The PCA3 score was significantly higher in men with biopsy Gleason score 7 or greater vs less than 7, greater than 33% vs 33% or fewer positive cores and significant vs indolent prostate cancer. Inclusion of PCA3 in multivariable models increased their predictive accuracy by up to 5.5%. Conclusions The PROGENSA PCA3 assay can aid in guiding biopsy decisions. It is superior to total prostate specific antigen, prostate specific antigen density and %free prostate specific antigen in predicting initial biopsy outcome, and may be indicative of prostate cancer aggressiveness.
In a large, international cohort, men with indications for prostate biopsy have an increased risk of high-grade prostate cancer in the presence of a family history of prostate cancer, second-degree ...prostate cancer, and first-degree breast cancer, controlling for other risk factors. This risk did not vary based on prostate-specific antigen level, and having additional affected relatives conferred an increased risk of high-grade prostate cancer on biopsy.
The risk of high-grade prostate cancer, given a family history of cancer, has been described in the general population, but not among men selected for prostate biopsy in an international cohort.
To estimate the risk of high-grade prostate cancer on biopsy based on a family history of cancer.
This is a multicenter study of men undergoing prostate biopsy from 2006 to 2019, including 12 sites in North America and Europe. All sites recorded first-degree prostate cancer family histories; four included more detailed data on the number of affected relatives, second-degree relatives with prostate cancer, and breast cancer family history.
Multivariable logistic regressions evaluated odds of high-grade (Gleason grade group ≥2) prostate cancer. Separate models were fit for family history definitions, including first- and second-degree prostate cancer and breast cancer family histories.
A first-degree prostate cancer family history was available for 15 799 men, with a more detailed family history for 4617 (median age 65 yr, both cohorts). Adjusted odds of high-grade prostate cancer were 1.77 times greater (95% confidence interval CI 1.57−2.00, p < 0.001, risk ratio RR = 1.40) with first-degree prostate cancer, 1.38 (95% CI 1.07−1.77, p = 0.011, RR = 1.22) for second-degree prostate cancer, and 1.30 (95% CI 1.01−1.67, p = 0.040, RR = 1.18) for first-degree breast cancer family histories. Interaction terms revealed that the effect of a family history did not differ based on prostate-specific antigen but differed based on age. This study is limited by missing data on race and prior negative biopsy.
Men with indications for biopsy and a family history of prostate or breast cancer can be counseled that they have a moderately increased risk of high-grade prostate cancer, independent of other risk factors.
In a large international series of men selected for prostate biopsy, finding a high-grade prostate cancer was more likely in men with a family history of prostate or breast cancer.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Nodal metastasis (N1) is a strong prognostic parameter in prostate cancer; however, lymph node evaluation is always incomplete.
To study the prognostic value of lymphatic invasion (L1) and whether it ...might complement or even replace lymph node analysis in clinical practice.
Retrospective analysis of pathological and clinical data from 14 528 consecutive patients.
Radical prostatectomy.
The impact of L1 and N1 on patient prognosis was measured with time to biochemical recurrence as the primary endpoint.
Nodal metastases were found in 1602 (12%) of 13 070 patients with lymph node dissection. L1 was seen in 2027 of 14 528 patients (14%) for whom lymphatic vessels had been visualized by immunohistochemistry. N1 and L1 continuously increased with unfavorable Gleason grade, advanced pT stage, and preoperative prostate-specific antigen (PSA) values (p<0.0001 each). N1 was found in 4.3% of 12 501 L0 and in 41% of 2027 L1 carcinomas (p<0.0001). L1 was seen in 11% of 9868 N0 and in 61% of 1360 N1 carcinomas (p<0.0001). Both N1 and L1 were linked to PSA recurrence (p<0.0001 each). This was also true for 17 patients with isolated tumor cells (ie, <200 unequivocal cancer cells without invasive growth) and 193 metastases ≤1mm. Combined analysis of N and L status showed that L1 had no prognostic effect in N1 patients but L1 was strikingly linked to PSA recurrence in N0 patients. N0L1 patients showed a similar outcome as N1 patients.
Analysis of lymphatic invasion provides comparable prognostic information than lymph node analysis. Even minimal involvement of the lymphatic system has pivotal prognostic impact in prostate cancer. Thus, a thorough search for lymphatic involvement helps to identify more patients with an increased risk for disease recurrence.
Already minimal amounts of tumor cells inside the lymph nodes or intraprostatic lymphatic vessels have a severe impact on patient prognosis.
To replace morbidity-prone lymph node analysis, we tested immunohistochemical analysis of lymphatic vessels to predict prognosis after radical prostatectomy. We found that minimal lymphatic invasion had a pivotal prognostic impact.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Delayed neurocognitive recovery (DNCR) is a common and serious complication after radical prostatectomy. We hypothesized that patients with DNCR in the early postoperative period would report reduced ...health-related quality of life (HRQoL) and more cognitive failures 12 months after surgery, compared with patients without DNCR.
We performed a 12-month follow-up on 367 patients who had been enrolled in a prospective observational trial to study the incidence of DNCR after radical prostatectomy. Patients were screened for preoperative cognitive impairment and depression. We defined DNCR as a decline in cognitive function between days 3 and 5 after surgery, compared with baseline assessments. We evaluated HRQoL and cognitive failures 12 months after surgery with the 36-item Short Form Health Survey and the Cognitive Failures Questionnaire. General linear models were used to analyze associations of DNCR with HRQoL and cognitive failures.
Delayed neurocognitive recovery in the early postoperative period was significantly associated with self-reported cognitive failures (B for no DNCR = - 0.411 95% CI: - 0.798;0.024, p = 0.038), but not with physical (B = 0.082 95% CI: - 0.021;0.186, p = 0.118) or mental HRQoL (B = - 0.044 95% CI: - 0.149;0.062, p = 0.417) 12 months after surgery. Preoperative depression screening scores were significantly associated with self-reported cognitive failures and both physical and mental HRQoL 12 months after surgery.
Delayed neurocognitive recovery in the early period after radical prostatectomy has a long-term impact on patients' daily lives by impairing memory, attention, action, and perception. Therefore, prevention of DNCR must be a priority for physicians and researchers. Consequent preoperative screening for depressive symptoms may facilitate early psycho-oncological intervention to improve postoperative HRQoL. Trials registration DRKS00010014 , date of registration: 21.03.2016, retrospectively registered.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract Background Several reports have shown that patients who undergo minimally invasive radical prostatectomy have a lower chance of undergoing pelvic lymph node dissection (PLND), irrespective ...of the disease characteristics. Objective We evaluated the rate and extension of PLND in patients who underwent robot-assisted radical prostatectomy (RARP). We tested the adherence of the indication for PLND to the European Association of Urology (EAU) guidelines. Design, setting, and participants Our study was a multi-institutional retrospective analysis of prospectively collected data on 2985 consecutive patients who underwent RARP at five high-volume European institutions. Patients were stratified according to preoperative cancer risk group. Intervention RARP. Outcome measurements and statistical analysis The rate and extent of PLND across different institutions were analyzed. Univariable and multivariable logistic regression models evaluated the association between preoperative variables and the probability of receiving PLND, as well as the presence of lymph node invasion (LNI). Finally, the probability of LNI was calculated for each patient, and the indication for PLND was compared with the EAU guidelines’ indications. Results and limitations A lymph node dissection was performed in 1777 patients (59.7%; 34.5% of low-risk patients, 64.9% of intermediate-risk patients, and 91.2% of high-risk patients). These rates were different across institutions: 5.0–41.4% in low-risk patients ( p < 0.001), 31.3–81.4% in intermediate-risk patients ( p < 0.001), and 84.6–96.4% in high-risk patients ( p = 0.06). The mean and median number of nodes removed was 10.8, and 122 patients (4.1%) had nodal metastases. At multivariable analysis, the institution represented an independent predictor of PLND ( p < 0.001). Of patients with current indication for PLND (EAU guidelines), 77.8% actually received the procedure. Limitations were the retrospective study design with different pathologic assessment and lack of follow-up data. Conclusions PLND is performed in a high proportion of patients undergoing RARP in high-volume centers in Europe for whom the procedure is indicated by the EAU guidelines, but significant differences exist among institutions. An effort toward a more rigorous standardization of PLND is advocated. Patient summary In this paper, we investigated the indication for and extension of pelvic lymph node dissection (PLND) in different institutions in Europe. Despite PLND being widely performed, significant variations with regard to PLND do exist among different institutions. Therefore, a thrust toward more rigorous attention to PLND is advocated.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Study Type – Therapy (case series)
Level of Evidence 4
What’s known on the subject? and What does the study add?
The widespread use of PSA testing resulted in a stage migration towards clinical ...organ‐confined prostate cancers at diagnosis during the last decade. However, our study of a large cohort demonstrates an increasing proportion of patients with non‐organ confined cancers after radical prostatectomy. These findings may be related to the introduction of new, non‐established treatment options for low‐risk prostate cancer patients during the last years and the growing adoption of RP in a multimodal treatment setting for locally advanced tumours.
OBJECTIVE
• To investigate the stage migration patterns during the last decade in European men treated with radical prostatectomy (RP).
PATIENTS AND METHODS
• Between 2000 and 2009, RP was performed in 8916 patients at a single European tertiary‐care institution.
• Age at diagnosis, clinical and pathological data were prospectively collected, and trends and proportions of preoperative and pathological findings were analysed over time.
RESULTS
• The median (mean) age of patients increased from 62 (62) to 63 (65) years between 2000 and 2009 (P < 0.001).
• When patients were stratified based on their clinical findings according to the D’Amico risk groups for disease progression, the proportion of low‐risk patients dropped from 66% in 2004 to 35% (P= 0.016) in the final year of the study period.
• Similarly, histopathological evaluation of RP specimens showed a decrease of favourable disease (organ confinement and Gleason 3 + 3 grade) from 53 to 17% (P= 0.008).
• This trend was accompanied by an increase in the number of patients with non‐organ‐confined prostate cancer (PCa) from 19% in 2003 to 33% in 2009 (P= 0.008).
• The restriction of the analyses in the present study to a single tertiary‐care centre could limit the generalizeability of the results.
CONCLUSIONS
• During the last decade, we observed an inverse stage migration trend in those European patients with PCa who were treated with RP.
• The recorded increase in patients with non‐organ‐confined disease after RP could be related to changes in patient selection and the growing adoption of RP in multimodal treatment settings for locally advanced tumours as well as the availability of new treatment alternatives for low‐risk disease.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
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