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.
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.
This study investigates how the COVID-19 pandemic (CP) impacted the timeline between initial diagnosis (ID) of prostate carcinoma and subsequent therapy consultation (TC) or radical prostatectomy ...(RP) due to the implementation of a "minimal contact concept," which postponed clinical examinations until the day of admission.
We analyzed patient data from a tertiary care center from 2018 to September 2021. The focus was on comparing the time intervals from ID to TC and from ID to RP before and during the CP.
Of 12,255 patients, 6,073 (61.6%) were treated before and 3,791 (38.4%) during the CP. The median time from ID to TC reduced from 37 days (IQR: 21 - 58d) pre-CP to 32 days (IQR: 20 - 50d) during CP (
< 0.001). Similarly, the time from ID to RP decreased from 98 days (IQR: 70 - 141d) to 75 days (IQR: 55 - 108d;
< 0.001) during the CP. There was a significant decrease in low-risk tumor cases at ID (18.9% vs. 21.4%;
= 0.003) and post-RP (4% vs. 6.7%;
< 0.001) during the CP.
Our findings suggest that the COVID-19 pandemic facilitated more timely treatment of prostate cancer, suggesting potential benefits for both low-risk and aggressive tumor management through expedited clinical procedures.
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.
Deletions of chromosome arm 13q belong to the most frequent molecular alterations in prostate cancer. To better understand the role of 13q deletion in prostate cancer we took advantage of our large ...prostate cancer tissue microarray comprising more than 12 000 cancer samples with full pathological and clinical follow‐up data. Fluorescence in situ hybridization with probes for ENOX1 (13q14.11) and the retinoblastoma gene (RB1, 13q14.2) was employed. A 13q deletion was found in 21% of 7375 analyzable cancers. Deletions were always heterozygous and associated with high Gleason grade (P < .0001), advanced tumor stage (P < .0001), high preoperative prostate‐specific antigen (PSA) levels (P = .0125), lymph node metastasis (P = .0377), positive resection margin (P = .0064), and early biochemical recurrence (P < .0001). 13q deletions were marginally more frequent in prostate cancers with negative ERG status (22.9%) than in ERG‐positive tumors (18.7%; P < .0001). Loss of 13q predicted patient prognosis independently from established prognostic parameters that are available at the time of biopsy (P = .0004), including preoperative PSA level, clinical tumor stage, and biopsy Gleason grade. In summary, the results of our study identify 13q deletion as a frequent event in prostate cancer, which is linked to an adverse phenotype and poor prognosis in this disease.
Epithelial splicing regulatory protein 1 (ESRP1) and 2 (ESRP2) regulate alternative splicing events of various pre-mRNAs. Some of these targets play a role in cancer-associated processes, including ...cytoskeleton reorganization and DNA-repair processes. This study was undertaken to estimate the impact of ESRP1 and ESRP2 alterations on prostate cancer patient prognosis.
A tissue microarray made from 17,747 individual cancer samples with comprehensive, pathological, clinical and molecular data was analyzed by immunohistochemistry for ESRP1 and ESRP2.
Nuclear staining for ESRP1 was seen in 38.6% (36.0% low, 2.6% high) of 12,140 interpretable cancers and in 41.9% (36.4% low, 5.3% high) of 12,962 interpretable cancers for ESRP2. Nuclear protein expression was linked to advanced tumor stage, high Gleason score, presence of lymph node metastasis, early biochemical recurrence, and ERG-positive cancers (p < 0.0001 each). Expression of ESRPs was significantly linked to 11 (ESRP1)/9 (ESRP2) of 11 analyzed deletions in all cancers and to 8 (ESRP1)/9 (ESRP2) of 11 deletions in ERG-negative cancers portending a link to genomic instability. Combined ESRPs expression analysis suggested an additive effect and showed the worst prognosis for cancers with high ESRP1 and ESRP2 expression. Multivariate analyses revealed that the prognostic impact of ESRP1, ESRP2 and combined ESRP1/ESRP2 expression was independent of all established pre- and postoperative prognostic features.
Our data show a striking link between nuclear ESRP expression and adverse features in prostate cancer and identifies expression of ESRP1 and/or ESRP2 as independent prognostic markers with a potential for routine application.
To evaluate the impact of time to castration resistance (TTCR) in metastatic hormone-sensitive prostate cancer (mHSPC) patients on overall survival (OS) in the era of combination therapies for mHSPC.
...Of 213 mHSPC patients diagnosed between 01/2013-12/2020 who subsequently developed metastatic castration resistant prostate cancer (mCRPC), 204 eligible patients were analyzed after having applied exclusion criteria. mHSPC patients were classified into TTCR <12, 12-18, 18-24, and >24 months and analyzed regarding OS. Moreover, further OS analyses were performed after having developed mCRPC status according to TTCR. Logistic regression models predicted the value of TTCR on OS.
Median follow-up was 34 months. Among 204 mHSPC patients, 41.2% harbored TTCR <12 months, 18.1% for 12-18 months, 15.2% for 18-24 months, and 25.5% for >24 months. Median age was 67 years and median PSA at prostate cancer diagnosis was 61 ng/ml. No differences in patient characteristics were observed (all p>0.05). According to OS, TTCR <12 months patients had the worst OS, followed by TTCR 12-18 months, 18-24 months, and >24 months, in that order (p<0.001). After multivariable adjustment, a 4.07-, 3.31-, and 6.40-fold higher mortality was observed for TTCR 18-24 months, 12-18 months, and <12 months patients, relative to TTCR >24 months (all p<0.05). Conversely, OS after development of mCRPC was not influenced by TTCR stratification (all p>0.05).
Patients with TTCR <12 months are at the highest OS disadvantage in mHSPC. This OS disadvantage persisted even after multivariable adjustment. Interestingly, TTCR stratified analyses did not influence OS in mCRPC patients.
Abstract Background To date, few data are available about the sequential use of the tyrosine kinase inhibitors (TKI) sorafenib and sunitinib in metastatic renal cell carcinoma (mRCC). Objective To ...investigate the effectiveness of the use of sunitinib after progression under sorafenib in mRCC. Design, setting, and participants A retrospective analysis of 30 patients with progressive mRCC, treated with sorafenib between May 2005 and February 2008. When radiologic progression was diagnosed, treatment was switched to sunitinib and continued until a further tumour progression occurred. Measurements Radiologic evaluation of the treatment results was performed every 3 mo according to the criteria for Response Evaluation Criteria in Solid Tumors (RECIST). Adverse effects and therapeutic abnormalities (eg, dose reduction) were documented during regular visits. Results and limitations Of the patients, 50% benefited from the secondary use of sunitinib. In detail, a radiologically confirmed new disease stabilisation or partial response was observed in seven and eight patients, respectively. Median progression-free survival was 8.7 mo and 10.3 mo under sorafenib and sunitinib, respectively. Overall, the median time from the initialisation of the first TKI until progression under therapy with the second TKI was 17.3 mo. To our knowledge, this is the second largest study reporting results of sequential therapy from sorafenib followed by sunitinib. However, the number of patients is still not extensive enough to settle this important question conclusively. Conclusions This study supports the hypothesis that sequential TKI therapy with the sorafenib followed by sunitinib has clinical validity in some patients with advanced renal cell carcinoma when progressive disease occurs under the initial TKI therapy.
Abstract Introduction The presence of circulating tumor cells (CTCs) is an established marker for prognosis in men with castration-resistant prostate cancer. A cutoff of ≥5 CTCs/7.5 ml blood in the ...CellSearch Epithelial Cell Test has been shown to stratify prognostic groups and predict outcome of abiraterone treatment. In contrast, the value of CTC detection in men with localized prostrate cancer before radical prostatectomy (RP) is unknown. Materials and methods A total of 152 patients treated with RP between 06/2009 and 09/2009 were included. Peripheral venous blood drawn the day before RP was evaluated for CTCs by the CellSearch system. The detection of CTCs was correlated with prostate-specific antigen (PSA) and the histopathological outcome of the RP specimen. A cutoff of 0 vs. ≥1 CTC/7.5 ml blood was defined as the threshold for positive vs. negative CTC status. Results Median age was 62 years and median PSA was 6.7 ng/dl. Staging revealed 62.5% pT2, 26.3% pT3a, and 11.2% pT3b tumors, and high-grade disease (≥Gleason 4+3) was determined in 25.6% of patients. CTCs were detected in 17 patients (11%) with a median CTC count/7.5 ml of 1 (range: 1–clusters with>100 epithelial cells) without significant correlations to PSA levels, pT stage, or Gleason scores. Postoperative pT stage was a significant predictor of biochemical recurrence (BCR) in univariable logistic regression models and as a composite measure together with positive CTC counts ( P <0.0001). CTC positivity alone tended to have a higher hazard ratio for BCR, but this was not statistically significant ( P = 0.1). After a median follow-up of 48 months, there was no significant difference in BCR-free survival between patients with or without CTCs ( P = 0.7). Conclusion Using the CellSearch system, we infrequently detected CTCs in patients with localized tumors before RP. The detection of CTCs did not correlate significantly with PSA, disease characteristics, or the development of BCR. However, larger cohorts with extended follow-up are needed to validate our findings.
B7‐H3 is a member of the B7 superfamily of immune checkpoint molecules. B7‐H3 up regulation has been linked to cancer development and progression in many tumors including prostate cancer. To clarify ...the potential utility of B7‐H3 as a prognostic biomarker, B7‐H3 expression was analyzed by immunohistochemistry in more than 17 000 prostate cancers. Normal prostatic glands were largely B7‐H3 negative, while membranous B7‐H3 immunostaining was seen in 47.0% of analyzed cancers. B7‐H3 immunostaining was weak in 12.3%, moderate in 21.1% and strong in 13.5% of cases. High B7‐H3 expression was associated with pT, Gleason score, lymph node metastasis, high Ki67 labeling index and early prostate‐specific antigen recurrence (P < 0.0001 each). High B7‐H3 expression was also linked to high androgen receptor expression and TMPRSS2:V‐ets avian erythroblastosis virus E26 oncogene homolog (ERG) fusions (P < 0.0001 each). Multivariate analyses showed a strong independent prognostic impact of high B7‐H3 expression in all cancers and in the ERG negative subgroup. Comparison with previously analyzed frequent chromosomal deletions revealed a close association with Phosphatase and Tensin Homolog deletions. Analysis of B7‐H3, alone or in combination with other markers, might be of clinical utility, especially in the subgroup of ERG negative prostate cancers.
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