Pilot study of salvage laparoscopic prostatectomy for the treatment of recurrent prostate cancer.

OBJECTIVE: • To evaluate feasibility, safety and oncological efficacy of salvage laparoscopic radical prostatectomy for pathology-proven biochemical recurrence after primary radiation therapy or cryotherapy for prostate cancer. MATERIALS AND METHODS: • This retrospective pilot study examined 15 patients from 2004 to 2010 with biochemical recurrence after external beam radiation therapy (N= 8), brachytherapy (N= 6) or cryotherapy (N= 1). • Patients were treated with salvage laparoscopic radical prostatectomy (11 conventional, four robotic-assisted) with bilateral pelvic dissection. RESULTS: • Median duration of surgery was 235 min. None of the following occurred: conversion to open surgery, transfusion, urethrovesical stenosis or perioperative or postoperative mortality. One patient presented with a rectal injury, repaired using uninterrupted sutures and a colostomy. One patient had anastomotic leak treated with prolonged Foley catheterization. • Pathological stage was pT2a in three, pT2b in three, pT3a in four, pT3b in three and pT4 in two patients; two patients had nodal metastasis. Within an 8-month median follow-up, 11 patients were disease-free and three had persistent postoperative prostate-specific antigen (PSA) elevation; the remaining patient experienced PSA recurrence after 21 months. • Seven patients achieved continence (no pads) by 8.4 months (median), one patient manifested severe incontinence corrected by implanting an artificial sphincter, and seven patients with a 12.6-month mean follow-up continued to need one or two pads per day. • Erectile dysfunction was present in five patients before surgery and in 14 patients after surgery. CONCLUSION: • Salvage laparoscopic radical prostatectomy seems to offer a safe therapeutic alternative for patients failing primary radiation or cryotherapy. However, larger studies with longer-term data are required.

Comparative effectiveness of prostate cancer surgical treatments: a population based analysis of postoperative outcomes.

PURPOSE: Enthusiasm for laparoscopic surgical approaches to prostate cancer treatment has grown despite limited evidence of improved outcomes compared with open radical prostatectomy. We compared laparoscopic prostatectomy with or without robotic assistance vs open radical prostatectomy in terms of postoperative outcomes and subsequent cancer directed therapy. MATERIALS AND METHODS: Using a population based cancer registry linked with Medicare claims we identified men 66 years old or older with localized prostate cancer who underwent radical prostatectomy from 2003 to 2005. Outcome measures were general medical/surgical complications and mortality within 90 days after surgery, genitourinary/bowel complications within 365 days, radiation therapy and/or androgen deprivation therapy within 365 days and length of hospital stay. RESULTS: Of the 5,923 men 18% underwent laparoscopic radical prostatectomy. Adjusting for patient and tumor characteristics, there were no differences in the rate of general medical/surgical complications (OR 0.93 95% CI 0.77-1.14) or genitourinary/bowel complications (OR 0.96 95% CI 0.76-1.22), or in postoperative radiation and/or androgen deprivation (OR 0.80 95% CI 0.60-1.08). Laparoscopic prostatectomy was associated with a 35% shorter hospital stay (p <0.0001) and a lower bladder neck/urethral obstruction rate (OR 0.74, 95% CI 0.58-0.94). In laparoscopic cases surgeon volume was inversely associated with hospital stay and the odds of any genitourinary/bowel complication. CONCLUSIONS: Laparoscopic prostatectomy and open radical prostatectomy have similar rates of postoperative morbidity and additional treatment. Men considering prostate cancer surgery should understand the expected benefits and risks of each technique to facilitate decision making and set realistic expectations.

Location and number of positive surgical margins as prognostic factors of biochemical recurrence after salvage radiation therapy after radical prostatectomy.

OBJECTIVE: To determine if the location and number of positive surgical margins (PSMs) after radical prostatectomy (RP) are associated with recurrence after salvage external beam radiation therapy (sEBRT). PATIENTS AND METHODS: We retrospectively reviewed the medical records of 60 patients with PSMs who underwent three-dimensional conformal sEBRT for biochemical recurrence (BCR) or clinically detected local recurrence after RP between 1996 and 2007. PSMs were categorized as present or absent at three locations, and patients were classified as having either one or more than one PSM. BCR after RP was defined as a prostate-specific antigen (PSA) level of ≥ 0.1 ng/mL. BCR after sEBRT was defined as a serum PSA level of ≥ 0.1 ng/mL above the PSA nadir after sEBRT. RESULTS: In all, 24 (40%) patients had more than one PSM. Overall, the most common location of a PSM was the posterior prostate with 40 (66%) patients having a positive posterior margin. The location of PSMs was not significantly associated with secondary BCR (global P= 0.8). There was a borderline result between the number of PSMs and BCR: men with more than one PSM were less likely to recur compared with those with only one PSM (hazard ratio 0.42; P= 0.067). CONCLUSIONS: This is the first study to specifically analyse location and number of PSMs as prognostic factors for men who undergo sEBRT. There was no evidence to suggest that the location of a PSM predicted secondary BCR. Further research is needed to determine whether the number of PSMs is an important predictor of BCR after sEBRT.

Chronology of erectile function in patients with early functional erections following radical prostatectomy.

INTRODUCTION: The association between erectile dysfunction (ED) and radical prostatectomy (RP) is well established. It is our clinical experience that some men who have functional erections in the days to weeks after RP go on to lose erectile function (EF) after the first 3 months postsurgery. AIM: To assess EF over a 12-month period in patients with functional erections at 3 months following RP. METHODS: As part of a large prospective quality-of-life (QOL) study of men undergoing RP at our institution, EF is measured postoperatively at regular time intervals using serial administration of the International Index of Erectile Function (IIEF) questionnaire. For study inclusion, patients had to have functional erections (a score 4 or 5 on IIEF question 3) at the third postoperative month, and have at least 12 months of follow-up. MAIN OUTCOME MEASURES: Assessment of EF and phosphodiesterase type 5 inhibitor (PDE5i) use at 3, 6, and 12 months after RP. RESULTS: At 3 months, 76 of 482 patients (16%) had functional erections. Between 3 to 6 months postoperatively, 20% of men deteriorated in their functional status. Of these men, 91% had functional erections at 1 year. Comparing patients who did not require PDE5i to obtain a functional erection at 3 months with those who did, the EF outcomes were superior at 6 months (80% vs. 72%, P = 0.74) and 12 months (100% vs. 88%, P = 0.33). CONCLUSION: The recovery of functional erections in the early postoperative phase, especially without the need for PDE5i, is a good prognostic indicator for EF at 12 months. However, a distinct cohort of men lose functional erections within 6 months after surgery. It is important to inform patients of this possibility, as it has an impact on their QOL and, potentially, on their compliance with post-RP therapy for ED.

Circulating prostate tumor cells detected by reverse transcription-PCR in men with localized or castration-refractory prostate cancer: concordance with CellSearch assay and association with bone metastases and with survival.

BACKGROUND: Reverse transcription-PCR (RT-PCR) assays have been used for analysis of circulating tumor cells (CTCs), but their clinical value has yet to be established. We assessed men with localized prostate cancer or castration-refractory prostate cancer (CRPC) for CTCs via real-time RT-PCR assays for KLK3 [kallikrein-related peptidase 3; i.e., prostate-specific antigen (PSA)] and KLK2 mRNAs. We also assessed the association of CTCs with disease characteristics and survival. METHODS: KLK3, KLK2, and PSCA (prostate stem cell antigen) mRNAs were measured by standardized, quantitative real-time RT-PCR assays in blood samples from 180 localized-disease patients, 76 metastatic CRPC patients, and 19 healthy volunteers. CRPC samples were also tested for CTCs by an immunomagnetic separation system (CellSearch; Veridex) approved for clinical use. RESULTS: All healthy volunteers were negative for KLK mRNAs. Results of tests for KLK3 or KLK2 mRNAs were positive (> or =80 mRNAs/mL blood) in 37 patients (49%) with CRPC but in only 15 patients (8%) with localized cancer. RT-PCR and CellSearch CTC results were strongly concordant (80%-85%) and correlated (Kendall tau, 0.60-0.68). Among CRPC patients, KLK mRNAs and CellSearch CTCs were closely associated with clinical evidence of bone metastases and with survival but were only modestly correlated with serum PSA concentrations. PSCA mRNA was detected in only 7 CRPC patients (10%) and was associated with a positive KLK mRNA status. CONCLUSIONS: Real-time RT-PCR assays of KLK mRNAs are highly concordant with CellSearch CTC results in patients with CRPC. KLK2/3-expressing CTCs are common in men with CRPC and bone metastases but are rare in patients with metastases diagnosed only in soft tissues and patients with localized cancer.

Pathological upgrading and up staging with immediate repeat biopsy in patients eligible for active surveillance.

PURPOSE: Active surveillance with selective delayed intervention is a treatment regimen used in patients with low risk prostate cancer. Decision making is based on pretreatment prostate specific antigen, clinical stage and prostate biopsy results. We reviewed our experience with immediate repeat biopsy in patients eligible for active surveillance with selective delayed intervention. MATERIALS AND METHODS: A retrospective review was done of the records of consecutive patients who underwent repeat biopsy within 3 months of a first positive biopsy from March 2002 to June 2007. Patients were considered eligible if they had prostate specific antigen less than 10 ng/ml, clinical stage T2a or less, Gleason pattern 3 or less, 3 or fewer positive cores and no single core with 50% or greater cancer involvement. RESULTS: A total of 104 patients met eligibility criteria. Of the 104 repeat biopsies performed 27 (26%) were negative, 59 (57%) had a Gleason score of 6 or less and 17 (16%) had a Gleason score of 7. One patient had a Gleason score of 9, while 10 of 104 (10%) had greater than 3 cores involved on repeat biopsy and 12 (12%) had 50% or greater involvement of at least 1 core. Of 104 cases (27%) 28 were upgraded and/or up staged. Treated cases that were upgraded and/or up staged were more likely to show higher pathological stage and grade at radical prostatectomy than those that were not (p = 0.003 and p = 0.001, respectively). CONCLUSIONS: Immediate repeat biopsy in cases of active surveillance with selective delayed intervention resulted in 27% being upgraded or up staged and those were more likely to show higher grade and stage disease at radical prostatectomy. We recommend repeat biopsy because it improved our discrimination of who are the best candidates for active surveillance with selective delayed intervention.

Indications for and anatomical extent of pelvic lymph node dissection for prostate cancer: practice patterns of uro-oncologists in North America.

PURPOSE: To investigate the prevailing practice of uro-oncologists regarding the indications for and extent of pelvic lymph node dissection (PLND) for prostate cancer. MATERIALS AND METHODS: A 9-question survey was sent as a hyperlink by electronic mail to all members of the Society of Urologic Oncology. Participants were asked about their surgical volume, indications for PLND, which nodal packets are dissected as delineated on anatomical schema, and type of surgical approach. RESULTS: Of 340 members, 183 urologists (58%) completed the survey. Of these, 43% were ≥ 10 years out of fellowship and 62% performed >50 radical prostatectomies per year. Of the surveyed surgeons, 45% performed PLND on all patients undergoing radical prostatectomy. The remainder used various risk-stratification schemas. A total of 32 different indications for PLND were reported, the most common being "intermediate risk" according to the American Urological Association's risk classification. As to extent of PLND, 15% perform a PLND limited to the external iliac, while 30% include the external iliac, obturator fossa, and hypogastric lymph nodes. Among surgeons using both open and robotic approaches, 19% reported that the indication for and extent of lymphadenectomy performed differ based on the surgical approach used. CONCLUSIONS: The results of this survey provide insight into the practice patterns of uro-oncologists regarding PLND and highlight the lack of uniformity in determining when and how a PLND should be performed. Collaborative efforts are needed to develop guidelines on this issue and are a necessary step toward standardization of reporting the outcomes of surgical clinical trials.

Positive surgical margins in radical prostatectomy: outlining the problem and its long-term consequences.

CONTEXT: This review focuses on positive surgical margins (PSM) in radical prostatectomy (RP). OBJECTIVE: To address the etiology, incidence, and oncologic impact of PSM and discuss technical points to help surgeons minimize their positive margin rate. An evidence-based approach to assist clinicians in counseling patients with a PSM is provided. EVIDENCE ACQUISITION: A literature search in English was performed using the National Library of Medicine database and the following key words: prostate cancer, surgical margins, and radical prostatectomy. Seven hundred sixty-eight references were scrutinized, and 73 were selected for rigorous review based on their pertinence, study size, and overall contribution to the field. EVIDENCE SYNTHESIS: In contemporary series, PSM are reported in 11-38% of patients undergoing RP. Although variability exists in the pathologic interpretation of surgical margins, PSM are associated with an increased hazard of biochemical recurrence (BCR) and local disease recurrence as well as the need for secondary cancer treatment. A posterolateral PSM appears to confer the greatest risk of recurrence, whereas the prognostic significance of positive apical margins remains controversial. The role of preoperative imaging and intraoperative frozen section analysis are being investigated to reduce margin positivity rates. Level-1 evidence indicates that adjuvant radiotherapy (RT) in men with PSM reduces BCR rates and clinical progression and possibly improves overall survival (OS). CONCLUSIONS: PSM in RP specimens are uniformly considered an adverse outcome. Regardless of approach (open or laparoscopic), attention to surgical detail is essential to minimize rates. For patients with a PSM destined to experience a cancer recurrence, RT is the only established treatment with curative potential. A randomized trial in patients with PSM comparing immediate postoperative RT to salvage RT is critically needed before definitive recommendations can be made.

Comparison of observed biochemical recurrence-free survival in patients with low PSA values undergoing radical prostatectomy and predictions of preoperative nomogram.

OBJECTIVES: A preoperative nomogram is an effective tool for assessing the risk of disease progression after radical prostatectomy for localized prostate cancer. To better understand the performance of nomograms for patients with a low prostate-specific antigen (PSA) level, we examined whether patients with a PSA level <2.5 ng/mL had outcomes different than predicted by a validated preoperative nomogram. METHODS: A cohort of 6130 patients from 2 referral centers was analyzed. Kaplan-Meier methods were used to estimate the recurrence-free probabilities stratified by PSA group (<2.5 vs >or=2.5 ng/mL). Cox proportional hazards regression analysis was used to evaluate whether the PSA grouping was associated with biochemical recurrence, controlling for preoperative nomogram probability. RESULTS: Of 6130 patients, 399 (6.5%) had a PSA level <2.5 ng/mL. Patients with a PSA level of 2.5 ng/mL developed recurrence (total 607/6130). With adjustment for the preoperative nomogram probability, no significant difference was found in recurrence by PSA grouping (hazard ratio 0.78 for PSA <2.5 vs >or=2.5 ng/mL; 95% confidence interval 0.42-1.48; P = .5). CONCLUSIONS: Patients with a low PSA comprise a small proportion of those treated, and most have palpable disease. Patients with especially low PSA values (