Jochen Walz

A Critical Analysis of the Current Knowledge of Surgical Anatomy Related to Optimization of Cancer Control and Preservation of Continence and Erection in Candidates for Radical Prostatectomy

CONTEXT Detailed knowledge of the anatomy of the prostate and adjacent tissues is mandatory during radical prostatectomy to ensure reliable oncologic and functional outcomes. OBJECTIVE To review critically and to summarize the available literature on surgical anatomy of the prostate and adjacent structures involved in cancer control, erectile function, and urinary continence. EVIDENCE ACQUISITION A search of the PubMed database was performed using the keywords radical prostatectomy, anatomy, neurovascular bundle, fascia, pelvis, and sphincter. Relevant articles and textbook chapters were reviewed, analyzed, and summarized. EVIDENCE SYNTHESIS Anatomy of the prostate and the adjacent tissues varies substantially. The fascia surrounding the prostate is multilayered, sometimes either fused with the prostate capsule or clearly separated from the capsule as a reflection of interindividual variations. The neurovascular bundle (NVB) is situated between the fascial layers covering the prostate. The NVB is composed of numerous nerve fibers superimposed on a scaffold of veins, arteries, and variable amounts of adipose tissue surrounding almost the entire lateral and posterior surfaces of the prostate. The NVB is also in close, cage-like contact to the seminal vesicles. The external urethral sphincter is a complex structure in close anatomic and functional relationship to the pelvic floor, and its fragile innervation is in close association to the prostate apex. Finally, the shape and size of the prostate can significantly modify the anatomy of the NVB, the urethral sphincter, the dorsal vascular complex, and the pubovesical/puboprostatic ligaments. CONCLUSIONS The surgical anatomy of the prostate and adjacent tissues involved in radical prostatectomy is complex. Precise knowledge of all relevant anatomic structures facilitates surgical orientation and dissection during radical prostatectomy and ideally translates into both superior rates of cancer control and improved functional outcomes postoperatively.

A Nomogram Predicting 10-Year Life Expectancy in Candidates for Radical Prostatectomy or Radiotherapy for Prostate Cancer

PURPOSE Candidates for definitive therapy for localized prostate cancer (PCa) should have life expectancy (LE) in excess of 10 years. However, LE estimation is difficult. To circumvent this problem, we developed a nomogram predicting 10-year LE for patients treated with either radical prostatectomy (RP) or external-beam radiation therapy (EBRT) and compared it with an existing tool. PATIENTS AND METHODS Between 1989 and 2000, 9,131 men were treated with either RP (n = 5,955) or EBRT (n = 3,176), without any secondary therapy and all deaths were considered unrelated to PCa. Age and Charlson comorbidity index (CCI) predicted 10-year LE in Cox regression models. We used 200 bootstrap resamples to internally validate the nomogram. RESULTS Median age was 66 years, median CCI was 1, median follow-up was 5.9 years and median actuarial survival was 13.8 years. Advanced age (P < .001), elevated CCI score (P < .001) and treatment type (EBRT v RP, P < .001) were independent predictors of poor 10 year LE. The nomogram predicting 10 year LE after either RP or EBRT was 84.3% accurate in split sample validation and was 2.9% (P = .007) more accurate than the existing tool. A cutoff of 70% or less was 84% accurate in identifying men who did not survive beyond 10 years. CONCLUSION Our nomogram can accurately identify those individuals who do not have sufficient LE to warrant definitive PCa treatment and can help optimizing therapy decision-making.

Clinical Significance of Epidermal Growth Factor Receptor Protein Overexpression and Gene Copy Number Gains in Prostate Cancer

Purpose: The epidermal growth factor receptor (EGFR) is a protein involved in the tumor progression of many cancer types and is an important therapeutic target. To determine its role in prostate cancer, we analyzed 2,497 prostate cancers on the DNA and protein level. Experimental Design: Tissue samples from each tumor were brought into a tissue microarray and analyzed by immunohistochemistry and fluorescence in situ hybridization. A subset of cancers was also sequenced for EGFR exon 18 to 21 mutations. Results: Detectable EGFR expression was found in 18% of cancers and was significantly associated with high grade, advanced stage, and high risk for prostate-specific antigen recurrence in univariate analysis (P < 0.0001, each). Fluorescence in situ hybridization analysis with a dual-labeling probe for centromere 7 and EGFR showed increased EGFR copy number in 3.3% of cases. EGFR copy number gains were mostly due to an overrepresentation of the entire chromosome and were associated with EGFR protein expression (P < 0.0001), high grade (P < 0.0001), and advanced stage (P = 0.0056). Only one cancer had a high-level amplification (>20 EGFR gene copies per cell). This amplification was heterogeneous, involving only ∼30% of the cancer volume. EGFR mutations were not found in 35 of the cases analyzed. Conclusion: Increased EGFR expression is often seen in prostate cancer and is associated with poor prognosis. The significant association of EGFR copy number gains with protein expression argues for the significant role of minimal gene copy number changes for protein expression. Although EGFR expression was not an independent prognostic variable, the potential utility of anti-EGFR medications might be worth further investigation in EGFR-expressing prostate cancer.

Nomogram Predicting the Probability of Early Recurrence After Radical Prostatectomy for Prostate Cancer

PURPOSE We developed a nomogram predicting the probability of early biochemical recurrence after radical prostatectomy because early recurrence predisposes to distant metastasis and prostate cancer related mortality. Identifying patients at risk for early recurrence may improve prognosis as early institution of adjuvant therapy may reduce the risk of progression. MATERIALS AND METHODS From January 1992 to December 2005, 2,911 patients underwent radical prostatectomy for localized prostate cancer. Cox regression models addressing biochemical recurrence after radical prostatectomy were used to identify significant predictors. Age, prostate specific antigen, pathological Gleason sum, surgical margin, extracapsular extension, seminal vesicle invasion and lymph node invasion were considered. A nomogram predicting the probability of biochemical recurrence-free survival within 2 years after radical prostatectomy was developed. Data from an independent center were used for external validation (2,875). RESULTS In both cohorts combined during the first 2 years 11.0% (639) of all patients experienced relapse which accounted for 58.5% of all observed biochemical recurrence. In the development cohort except for age all covariates represented significant predictors of biochemical recurrence after radical prostatectomy. Pathological Gleason sum 7 or greater, seminal vesicle invasion and lymph node invasion were the most powerful predictors of biochemical recurrence. The accuracy (c-index) of the nomogram predicting biochemical recurrence-free survival within 2 years after radical prostatectomy was 0.82 in the external validation cohort. CONCLUSIONS Two-thirds of all instances of relapse occur during the first 2 years after radical prostatectomy. Those patients can be highly accurately identified with our nomogram. They might benefit the most from adjuvant treatment and could be the ideal candidates for adjuvant treatment trials.

A critical appraisal of logistic regression-based nomograms, artificial neural networks, classification and regression-tree models, look-up tables and risk-group stratification models for prostate cancer

To evaluate several methods of predicting prostate cancer‐related outcomes, i.e. nomograms, look‐up tables, artificial neural networks (ANN), classification and regression tree (CART) analyses and risk‐group stratification (RGS) models, all of which represent valid alternatives.

Pathological results and rates of treatment failure in high‐risk prostate cancer patients after radical prostatectomy

Study Type – Therapy (outcomes research)

Clinicians are poor raters of life-expectancy before radical prostatectomy or definitive radiotherapy for localized prostate cancer

To test the accuracy of predicting life‐expectancy (LE) among 19 raters, as the accurate prediction of LE in candidates for definitive therapy for localized prostate cancer is crucial, and little is known of the ability of clinicians to predict LE.

Identifying the Best Candidate for Radical Prostatectomy Among Patients with High-Risk Prostate Cancer

BACKGROUND The current role of radical prostatectomy (RP) in patients with high-risk disease remains controversial. OBJECTIVE To identify which high-risk prostate cancer (PCa) patients might have favorable pathologic outcomes when surgically treated. DESIGN, SETTING, AND PARTICIPANTS We evaluated 1366 patients with high-risk PCa (ie, at least one of the following risk factors: prostate-specific antigen [PSA]>20 ng/ml, cT3, biopsy Gleason 8-10) treated with RP and pelvic lymph node dissection (PLND) at eight European centers between 1987 and 2009. A favorable pathologic outcome was defined as specimen-confined (SC) disease-namely, pT2-pT3a, node negative PCa with negative surgical margins. INTERVENTION All patients underwent radical retropubic prostatectomy and PLND. MEASUREMENTS Univariable and multivariable logistic regression models tested the association between predictors and SC disease. A logistic regression coefficient-based nomogram was developed and internally validated using 200 bootstrap resamples. The Kaplan-Meier method was used to depict biochemical recurrence (BCR) and cancer-specific survival (CSS) rates. RESULTS AND LIMITATIONS Overall, 505 of 1366 patients (37%) had SC disease at RP. All preoperative variables (ie, age and PSA at surgery, clinical stage, and biopsy Gleason sum) were independent predictors of SC PCa at RP (all p≤0.04). Patients with SC disease had significantly higher 10-yr BCR-free survival and CSS rates than patients without SC disease at RP (66% vs 47% and 98 vs 88%, respectively; all p<0.001). A nomogram including PSA, age, clinical stage, and biopsy Gleason sum demonstrated 72% accuracy in predicting SC PCa. This study is limited by its retrospective design and by the lack of an external validation of the nomogram. CONCLUSIONS Roughly 40% of patients with high-risk PCa have SC disease at final pathology. These patients showed excellent long-term outcomes when surgically treated, thus representing the ideal candidates for RP as the primary treatment for PCa. Prediction of such patients is possible using a nomogram based on routinely available clinical parameters.

Radical prostatectomy improves progression‐free and cancer‐specific survival in men with lymph node positive prostate cancer in the prostate‐specific antigen era: a confirmatory study

Study Type – Therapy (outcomes research)
Level of Evidence 2b

Critical assessment of tools to predict clinically insignificant prostate cancer at radical prostatectomy in contemporary men

Overtreatment of prostate cancer (PCa) is a concern, especially in patients who might qualify for the diagnosis of insignificant prostate cancer (IPCa). The ability to identify IPCa prior to definitive therapy was tested.