Anatomically versus biologically unifocal prostate cancer: a pathological evaluation in the context of focal therapy.

OBJECTIVES: Since tumor focality in prostate cancer continues to be considered a major limitation for focal prostate therapy, in this study we attempted to compare the pathological features and the proportion of patients with anatomically unifocal versus biologically unifocal tumors (i.e. multifocal prostate cancer in which the secondary nonindex elements are small, low grade and clinically insignificant) who were suitable for focal therapy. METHODS: Ninety-five consecutive whole mount laparoscopic radical prostatectomy samples underwent pathological assessment (from January 2007 to November 2009). Tumor focality, laterality, Gleason score and volume of individual foci, total tumor volume, pathological stage and surgical margin status were assessed. The index lesion was defined as the largest by volume. Patients suitable for focal ablation were defined as having tumors that were unifocal, organ confined, with a Gleason score (GS) up to 7 prostate cancer, or multifocal, organ confined, GS up to 7 prostate cancer, with one large index lesion and the remaining foci demonstrating features of clinically insignificant disease (total tumor volume of all secondary foci ≤0.5 cm(3) with GS ≤ 6). RESULTS: Patients with biologically unifocal cancer had significantly lower total tumor volume (3.26 versus 7.28 cm(3); p < 0.001), index lesion volume (2.9 versus 7.16 cm(3); p < 0.001), rates of seminal vesicle invasion (4% versus 34%; p < 0.001), rates of positive surgical margins (22.4% versus 52.1%; p < 0.001) and rates of 4+3 GS tumors (10.2% versus 29.1%; p = 0.018). The proportion of patients suitable for focal therapy was higher in the biologically unifocal versus anatomically unifocal cancer group, although without reaching statistical significance (65.3% versus 45.8%; p = 0.11). CONCLUSIONS: Patients with biologically unifocal tumors have better pathological outcome than those with anatomically unifocal disease. At present the assumption that multifocality should a priori exclude patients from any organ-preserving prostate cancer treatment is only theoretical and needs to be validated by future clinical trials since there are a large proportion of patients with multifocal disease apparently suitable for focal prostate therapy.

Trends in pathologic outcomes after introduction of active surveillance in the UK: implication for focal therapy.

BACKGROUND: We aimed to evaluate the trends in pathologic outcomes of clinically localized prostate cancer treated with radical prostatectomy prior to and after national guidelines placing active surveillance as the primary management in men with low-risk prostate cancer. Further, we examined whether there was a coincident change in the proportion of men potentially suitable for focal therapy. METHODS: All cancer foci in 195 whole mount radical prostatectomy samples during two periods (Period 1: 07/2001-10/2003, n = 100 and Period 2: 01/2007-11/2009, n = 95) were examined. Individual tumor volumes, Gleason grade, and extracapsular extension/positive surgical margins were evaluated. The index lesion was defined as the largest by volume. RESULTS: There was a statistically significant increase in the proportion of Gleason score ≥7 tumors (31-69%; P < 0.001) and pathologically non-organ confined disease (21-37%; P = 0.008), between period 1 and 2, respectively. The proportion of patients with unifocal prostate cancer potentially suitable for focal ablation was stable (14-13.7%; P = 0.9). Although there was a decrease in the proportion of patients potentially suitable for index lesion ablation (51-43%; P = 0.4) and unilateral prostate cancer potentially suitable for hemi-ablation (11-6.3%; P = 0.3), these differences were not statistically significant. CONCLUSION: The increasing use of active surveillance in the UK may be responsible for a trend towards higher grade and stage prostate cancer in whole mount specimens. Despite this, there remain a significant proportion of men who currently undergo radical surgery who may be suitable for focal therapy, if that included index lesion ablation.

Evolution of care pathway for laparoscopic radical prostatectomy.

PURPOSE: We report results of the introduction of a laparoscopic radical prostatectomy (LRP) care pathway. This included the introduction of a transversus abdominis plane (TAP) local anesthetic block and other measures to reduce the impact of factors known to delay postoperative recovery. Outcomes including pain, analgesic requirements, complications, and length of stay are reported. PATIENTS AND METHODS: Two hundred consecutive patients undergoing LRP from 2008 to 2010 were prospectively studied. A detailed perioperative care pathway was developed and implemented. The pathway was modified after a pain audit to include bilateral transversus abdominis plane regional anesthetic blockade. Same day discharge criteria were applied to suitable patients. Demographics and perioperative and follow-up data were prospectively collected and recorded on a database. RESULTS: Overall, 78% of cases were discharged after 1 night stay; 14 patients were managed as true day cases without overnight stay. Operative time (P<0.0001), intraoperative blood loss (P=0.018), %≤ 1 day stay (P=0.0091), transfusion, and conversion rate (nil in latter 100 cases) all improved significantly in the second 100 group of patients compared with the first 100 cases. The introduction of TAP blocks led to significant reductions of mean intraoperative and postoperative opiate use (17.3 mg to 1.3 mg and 1.9 mg to 0.2 mg morphine, respectively) without any significant effect on perceived pain. True day cases did not experience a significantly different rate of complications than the whole cohort. CONCLUSIONS: Through a structured care pathway incorporating the TAP block, 1 night stay laparoscopic prostatectomy can be safely delivered with reduced inpatient stay costs. In selected patients, day-case prostatectomy is feasible.

Margin status after laparoscopic radical prostatectomy and the index lesion: implications for preoperative evaluation of tumor focality in prostate cancer.

PURPOSE: The objective of this study was to evaluate the impact of tumor focality on positive surgical margins (PSM) after laparoscopic radical prostatectomy. PATIENTS AND METHODS: Ninety-five consecutive whole-mount laparoscopic radical prostatectomy samples (January 2007 to November 2009) were evaluated for tumor focality, laterality, Gleason score, and volume of individual foci, total tumor volume, pathologic stage, and surgical margin status. RESULTS: Thirty-nine percent, 36%, and 25% were in low, intermediate, and high D'Amico risk categories. Thirty-three percent (31/95) had PSM. Overall, 269 tumor foci were identified. The incidence of PSM within lesions ≤ 0.5 cc and ≤ 0.2 cc was 1.2% (2/160) and 0% (0/132), respectively. Among the 71 multifocal cases, 19 (27%) exhibited PSM. In 13 of these, the index lesion appeared at the inked surface (mean volume 5.4 cc, range 0.63-26.9 cc) compared with 6 in which both index and satellite foci appeared at the inked margins. Mean volume of these satellite foci was 1.06 cc (range 0.22-2 cc); three had Gleason score 6 and three had Gleason score 7 (3+4). CONCLUSIONS: PSM is usually attributed to the index lesion and lesions larger than commonly used thresholds for clinically significant lesion volumes. Because such lesions might be detected by multiparametric magnetic resonance imaging (MRI) or template mapping biopsies, the information from these staging modalities could be used intraoperatively to reduce PSM.

Focal therapy for prostate cancer: opportunities and uncertainties.

Prostate cancer is the most common cancer and the second most common cause of cancer-related death in men. Screening with prostate specific antigen (PSA) has led to a clinical and pathological stage migration such that currently most men diagnosed with prostate cancer have clinically localized disease potentially offering opportunity for curative intervention. On the other hand, the benefit of radical therapy in terms of reducing overall mortality in PSA-screened populations has been controversial with concerns being raised about over-diagnosis and over-treatment. Treatment of prostate cancer is associated with risk and complications that negatively affect the quality of life of men with localized disease. Recently, a new treatment paradigm has been proposed which is called focal therapy, defined as an individualized treatment by which only known disease is targeted and ablated while preserving normal tissue. This review will attempt to describe the opportunities and uncertainties behind this proposed paradigm shift.

Tumor focality in prostate cancer: implications for focal therapy.

In recent years, there has been a growing interest in focal treatment for prostate cancer. Although widely used for the treatment of tumors of the breast and kidney, focal treatment for prostate cancer remains a controversial area. Criticism of focal prostate therapy has been based on the fact that prostate cancer is a multifocal disease. Until now, little attention has been paid to distinguishing between men with unifocal and those with multifocal disease because such information has little clinical relevance when treatment is aimed at the whole gland irrespective of the volume or number of cancers in the prostate. In this Review, we summarize existing knowledge and examine the issue of prostate cancer focality in the context of focal treatment.

Retroperitoneal lymph node dissection after chemotherapy in patients with elevated tumour markers: indications, histopathology and outcome.

OBJECTIVE: To evaluate the factors affecting outcome and the pathological findings in patients who had retroperitoneal lymph node dissection (pcRPLND) after chemotherapy with elevated tumour markers, as such patients have an unfavourable prognosis, with further salvage chemotherapy being the usual treatment of choice. PATIENTS AND METHODS: Information on the preoperative treatment, tumour markers, histopathology and outcome data of the patients who had pcRPLND were extracted from the hospital databases. Survival was analysed using the Kaplan-Meier method and multivariate analysis with Cox regression model. RESULTS: In all, 358 patients had pcRPLND between September 1992 and April 2006, by one surgeon. In 48 patients the tumour markers were elevated at the time of surgery, they were on a 'rising trend' in 26 (54%) and 'downward or stable' trend in 22 (46%). The overall incidence of active germ cell tumour, differentiated teratoma and necrosis in the resected specimens was 58%, 25% and 17%, respectively. The median follow-up was 51.5 months and the overall 5-year survival was 69%. The favourable prognostic factors assessed by univariate analysis were elevation of alpha-fetoprotein alone, complete resection of residual disease, histological finding of differentiated teratoma in the resected tissues and normalization of tumour markers after pcRPLND. By multivariate analysis the only statistically significant independent survival factor was the normalization of the tumour markers after pcRPLND. CONCLUSION: For selected patients with elevated tumour markers after chemotherapy, RPLND can offer a significant chance of cure with no need for further chemotherapy. The patients most likely to benefit are those with elevations of alpha-fetoprotein alone. In this group, pcRPLND can offer the prospect of long-term survival and should be considered in the management of selected patients.

Therapy insight: prophylaxis, monitoring and treatment of perioperative myocardial ischemia with emphasis on urological surgery.

Unrecognized or silent perioperative myocardial ischemia is common in patients who undergo high-risk surgery, including cystectomy, and could predict cardiac morbidity and mortality in postoperative patients. This disorder is not merely a marker of extensive coronary disease but has a close association with perioperative myocardial infarction (PMI). In a review of published data, including meta-analyses, in the context of high-risk urological surgery, up to 50% of PMIs were found to go unrecognized if only clinical signs and symptoms are considered. Prevention and treatment of these previously unrecognized cardiac events might significantly reduce long-term morbidity and mortality. The emergence of reliable markers of PMI, such as increased levels of troponin I, could help in the detection of events that would have otherwise remained unnoticed. In this Review we examine the effect of these developments in the context of high-risk urological surgery. Changes to preoperative assessment, perioperative management, and prophylaxis of PMI are critically assessed. We performed a prospective audit using postoperative troponin I levels to assess the rate of silent perioperative myocardial ischemia and infarction. An increasingly proactive attitude towards perioperative monitoring for myocardial ischemia and infarction has evolved, and postoperative serial screening with troponin I might be beneficial in high-risk patients undergoing major urological surgery.

Characteristics of incidental prostatic adenocarcinoma in contemporary radical cystoprostatectomy specimens.

OBJECTIVES: To investigate the relationship between prostate-specific antigen (PSA) level and tumour volume for incidental adenocarcinoma of the prostate found in cystoprostatectomy (CP) specimens, and to analyse the incidence of clinically significant prostate cancers in CP specimens and the biochemical recurrence of incidental prostate cancers on short-term follow up. PATIENTS AND METHODS: Complete data from 97 of 105 prostates from CP specimens were available. Prostates were thoroughly analysed and sectioned at 2 mm intervals. PSA levels and the findings at digital rectal examination before surgery were obtained prospectively. None of the patients had any evidence of prostate cancer before CP. RESULTS: Incidental prostate cancer was detected in 58 of 97 (60%) of the CP specimens; of these, 31 (53%) were significant according to the definition of Stamey et al. There was a weak correlation between tumour volume and PSA level, weighted solely by the four larger-volume cancers. The median PSA level for patients with and without prostate cancer was not significantly different (3.1 vs 1.1 ng/mL, P = 0.06). The follow-up of the 35 patients alive with prostate cancer showed four PSA recurrences (PSA >0.02 ng/mL) with one distant metastasis after a median follow-up of 3 years. None of the patients with insignificant tumours developed biochemical recurrence. CONCLUSIONS: The weak correlation between PSA level and tumour volume in these patients supports the argument that PSA is largely produced by benign prostatic hyperplasia and is therefore a poor screening tool for asymptomatic healthy men. Most incidental prostate cancers in CP specimens are significant, contrary to previous analyses, but have little practical importance in terms of oncological outcome.

Lymphoepithelioma-like carcinoma of the urinary bladder--diagnostic and clinical implications.

BACKGROUND: A 57-year-old man presented with a 4-week history of intermittent, painless frank hematuria. There were no other symptoms. He had no previous urologic history, is a nonsmoker, and works as a manual laborer. INVESTIGATIONS: Physical examination, ultrasound of the urinary tract, and intravenous urography were all unremarkable. Urine microscopy confirmed more than 5 red blood cells per high-power field, but no malignant cells were seen on cytologic assessment. Flexible cystoscopy revealed a 3 cm, partially solid, solitary lesion on the right lateral wall of the bladder. The tumor was completely resected under general anesthesia. DIAGNOSIS: Histologically, the tumor was described as a G3 pT1 transitional cell carcinoma of the bladder. MANAGEMENT: Following the resection of a solitary recurrence 6 weeks after the initial tumor resection, the patient underwent a standard course of intravesical bacillus Calmette-Guérin therapy. Despite this, another tumor was identified 3 months later. Histologically, this tumor was described as a lymphoepithelioma-like carcinoma, of at least grade G3pT1. The patient underwent radical cystoprostatectomy with ileal conduit formation; no adjuvant systemic chemotherapy was given in light of complete tumor resection. The patient is under continuing, close clinical and radiologic observation and remains free of disease recurrence, 36 months postoperatively.

The total percentage of biopsy cores with cancer improves the prediction of pathological stage after radical prostatectomy.

OBJECTIVE: To examine whether the simple variable 'percentage of cancer-positive biopsy cores' is a significant predictor of true pathological stage after radical prostatectomy and can be used to improve pathological stage prediction by simple means. PATIENTS AND METHODS: In all, 375 patients had a radical prostatectomy for localized prostate cancer in two UK centres; 260 had complete preoperative staging information. Logistic regression was used and predicted probability graphs constructed to assess predictors of pathological stage. RESULTS: In this study, only PSA (P = 0.004) and percentage cancer-positive biopsy cores (P < 0.001) were significant predictors of pathological stage. The final model was an acceptable classifier for pathological stage (area under the receiver operating characteristic curve 0.76, specificity 85%, sensitivity 47%). A patient with a PSA of 10 ng/mL and one of six cores positive for cancer would have a predicted probability of extraprostatic disease of 20%, whereas the same patient with all six biopsy cores positive would have a predicted probability of extraprostatic disease of 80%. CONCLUSIONS: The percentage of cancer-positive biopsy cores significantly predicts the disease stage after radical prostatectomy. This variable is easy to obtain by the clinician and avoids the need to estimate the percentage of biopsy tissue infiltrated by cancer. This readily available information can easily be computed and may help to counsel patients about realistic expectations of organ-confined disease in relation to surgery as a treatment option.