Murugesan Manoharan

Careful Selection and Close Monitoring of Low-Risk Prostate Cancer Patients on Active Surveillance Minimizes the Need for Treatment

BACKGROUND With the advent of prostate-specific antigen (PSA) screening and the increase in the number of transrectal ultrasound-guided biopsy cores, there has been a dramatic rise in the incidence of low-risk prostate cancer (LRPC). Because > 97% of men with LRPC are likely to die of something other than prostate cancer, it is critical that patients give thought to whether early curative treatment is the only option at diagnosis. OBJECTIVE To identify a group of men with LRPC who may not require initial treatment and monitor them on our active surveillance (AS) protocol, to determine the percentage treated and the outcome and to analyze the quality-of-life data. DESIGN, SETTING, AND PARTICIPANTS We defined patients eligible for AS as Gleason ≤ 6, PSA ≤ 10, and two or fewer biopsy cores with ≤ 20% tumor in each core. MEASUREMENTS Kaplan Meier analysis was used to predict the 5-year treatment free survival. Logistic regression determined the predictors of treatment. Data on sexual function, continence, and outcome were obtained and analyzed. RESULTS AND LIMITATIONS The AS cohort consisted of 230 patients with a mean age of 63.4 yr; 86% remained on AS for a mean follow-up of 44 mo. Thirty-two of the 230 patients (14%) were treated for a mean follow-up of 33 mo. Twelve had a total prostatectomy (TP). The pathologic stage of these patients was similar to initially treated TP patients with LRPC. Fourteen underwent radiation therapy, and six underwent androgen-deprivation therapy. Fifty percent of patients had no tumor on the first rebiopsy, and only 5% of these patients were subsequently treated. PSA doubling time and clinical stage were not predictors of treatment. No patient progressed after treatment. Among the AS patients, 30% had incontinence, yet < 15% were bothered by it. As measured by the Sexual Health Inventory for Men, 49% of patients had, at a minimum, moderate (≤ 16) erectile dysfunction. CONCLUSIONS If guidelines for AS are narrowly defined to include only patients with Gleason 6, tumor volume ≤ 20% in one or two biopsy cores, and PSA levels ≤ 10, few patients are likely to require treatment. Progression-free survival of those treated is likely to be equivalent to patients with similar clinical findings treated at diagnosis.

Active surveillance; a reasonable management alternative for patients with prostate cancer: the Miami experience

To examine the outcome of patients diagnosed with ‘low‐risk’ prostate cancer managed by active surveillance (AS).

ICUD-EAU International Consultation on Bladder Cancer 2012: Urinary diversion.

CONTEXT A summary of the 2nd International Consultation on Bladder Cancer recommendations on the reconstructive options after radical cystectomy (RC), their outcomes, and their complications. OBJECTIVE To review the literature regarding indications, surgical details, postoperative care, complications, functional outcomes, as well as quality-of-life measures of patients with different forms of urinary diversion (UD). EVIDENCE ACQUISITION An English-language literature review of data published between 1970 and 2012 on patients with UD following RC for bladder cancer was undertaken. No randomized controlled studies comparing conduit diversion with neobladder or continent cutaneous diversion have been performed. Consequently, almost all studies used in this report are of level 3 evidence. Therefore, the recommendations given here are grade C only, meaning expert opinion delivered without a formal analysis. EVIDENCE SYNTHESIS Indications and patient selection criteria have significantly changed over the past 2 decades. Renal function impairment is primarily caused by obstruction. Complications such as stone formation, urine outflow, and obstruction at any level must be recognized early and treated. In patients with orthotopic bladder substitution, daytime and nocturnal continence is achieved in 85-90% and 60-80%, respectively. Continence is inferior in elderly patients with orthotopic reconstruction. Urinary retention remains significant in female patients, ranging from 7% to 50%. CONCLUSIONS RC and subsequent UD have been assessed as the most difficult surgical procedure in urology. Significant disparity on how the surgical complications were reported makes it impossible to compare postoperative morbidity results. Complications rates overall following RC and UD are significant, and when strict reporting criteria are incorporated, they are much higher than previously published. Fortunately, most complications are minor (Clavien grade 1 or 2). Complications can occur up to 20 yr after surgery, emphasizing the need for lifelong monitoring. Evidence suggests an association between surgical volume and outcome in RC; the challenge of optimum care for elderly patients with comorbidities is best mastered at high-volume hospitals by high-volume surgeons. Preoperative patient information, patient selection, surgical techniques, and careful postoperative follow-up are the cornerstones to achieve good long-term results.

The Learning Curve of Robot-Assisted Radical Cystectomy: Results from the International Robotic Cystectomy Consortium

BACKGROUND Robot-assisted radical cystectomy (RARC) has evolved as a minimally invasive alternative to open radical cystectomy for patients with invasive bladder cancer. OBJECTIVE We sought to define the learning curve for RARC by evaluating results from a multicenter, contemporary, consecutive series of patients who underwent this procedure. DESIGN, SETTING, AND PARTICIPANTS Utilizing the International Robotic Cystectomy Consortium database, a prospectively maintained and institutional review board-approved database, we identified 496 patients who underwent RARC by 21 surgeons at 14 institutions from 2003 to 2009. MEASUREMENTS Cut-off points for operative time, lymph node yield (LNY), estimated blood loss (EBL), and margin positivity were identified. Using specifically designed statistical mixed models, we were able to inversely predict the number of patients required for an institution to reach the predetermined cut-off points. RESULTS AND LIMITATIONS Mean operative time was 386 min, mean EBL was 408 ml, and mean LNY was 18. Overall, 34 of 482 patients (7%) had a positive surgical margin (PSM). Using statistical models, it was estimated that 21 patients were required for operative time to reach 6.5h and 8, 20, and 30 patients were required to reach an LNY of 12, 16, and 20, respectively. For all patients, PSM rates of <5% were achieved after 30 patients. For patients with pathologic stage higher than T2, PSM rates of <15% were achieved after 24 patients. CONCLUSIONS RARC is a challenging procedure but is a technique that is reproducible throughout multiple centers. This report helps to define the learning curve for RARC and demonstrates an acceptable level of proficiency by the 30th case for proxy measures of RARC quality.

Pathologic Prostate Cancer Characteristics in Patients Eligible for Active Surveillance: A Head-to-Head Comparison of Contemporary Protocols

BACKGROUND Although the rationale for active surveillance (AS) in patients with low-risk prostate cancer is well established, eligibility criteria vary significantly across different programs. OBJECTIVE To compare the ability of contemporary AS criteria to identify patients with certain pathologic tumor features based on the results of an extended transrectal prostate biopsy. DESIGN, SETTINGS, AND PARTICIPANTS The study cohort included 391 radical prostatectomy patients who had prostate cancer with Gleason scores ≤ 6 on transrectal biopsy with ≥ 10 cores. INTERVENTION Radical prostatectomy without neoadjuvant treatment. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS We identified patients who fulfilled the inclusion criteria of five AS protocols including those of Epstein, Memorial Sloan-Kettering Cancer Center, Prostate Cancer Research International: Active Surveillance (PRIAS), University of California, San Francisco, and University of Miami (UM). We evaluated the ability of these criteria to predict three pathologic end points: insignificant disease defined using a classical and updated formulation, and organ-confined Gleason ≤ 6 prostate cancer. Measures of diagnostic accuracy and areas under the receiver operating curve were calculated for each protocol and compared. RESULTS AND LIMITATIONS A total of 75% of the patients met the inclusion criteria of at least one protocol; 23% were eligible for AS by all studied criteria. The PRIAS and UM criteria had the best balance between sensitivity and specificity for both definitions of insignificant prostate cancer and a higher discriminative ability for the end points than any criteria including patients with two or more positive cores. The Epstein criteria demonstrated high specificity but low sensitivity for all pathologic end points, and therefore the discriminative ability was not superior to those of other protocols. CONCLUSIONS Significant variations exist in the ability of contemporary AS criteria to predict pathologically insignificant prostate cancer at radical prostatectomy. These differences should be taken into account when making treatment choices in patients with low-risk prostate cancer.

Surgical Margin Status After Robot Assisted Radical Cystectomy: Results From the International Robotic Cystectomy Consortium

PURPOSE Positive surgical margins at radical cystectomy confer a poor prognosis. We evaluated the incidence and predictors of positive surgical margins in patients who underwent robot assisted radical cystectomy for bladder cancer. MATERIALS AND METHODS Using the International Robotic Cystectomy Consortium database we identified 513 patients who underwent robot assisted radical cystectomy, as done by a total of 22 surgeons at 15 institutions from 2003 to 2009. After stratification by age group, gender, pathological T stage, nodal status, sequential case number and institutional volume logistic regression was used to correlate variables with the likelihood of a positive surgical margin. RESULTS Of the 513 patients 35 (6.8%) had a positive surgical margin. Increasing 10-year age group, lymph node positivity and higher pathological T stage were significantly associated with an increased likelihood of a positive margin (p = 0.010, <0.001 and p <0.001, respectively). Gender, sequential case number and institutional volume were not significantly associated with margin positivity. The rate of margin positive disease at cystectomy was 1.5% for pT2 or less, 8.8% for pT3 and 39% for pT4 disease. CONCLUSIONS Positive surgical margin rates at robot assisted radical cystectomy for advanced bladder cancer were similar to those in open cystectomy series in a large, multi-institutional, prospective cohort. Sequential case number, a surrogate for the learning curve and institutional volume were not significantly associated with positive margins at robot assisted radical cystectomy.

Trends in Gleason Score: Concordance Between Biopsy and Prostatectomy over 15 Years

OBJECTIVES To assess the changes in the concordance rate of prostate biopsy and radical prostatectomy (RP) Gleason score (GS) over 15 years. METHODS We reviewed 1670 consecutive patients who underwent RP between 1992 and 2006. We excluded patients who underwent neoadjuvant hormone therapy or salvage RP, or who had incomplete data. Patients who had RP during 1992 through 1996, 1997 through 2001, and 2002 through 2006 were assigned to groups 1, 2, and 3, respectively. All clinical and pathological data were collected retrospectively. We defined overgrading as a biopsy GS higher than the RP Gleason score. Undergrading was a biopsy GS less than the RP Gleason score. The GS concordance between biopsy and RP was evaluated by kappa coefficient. RESULTS A total of 1363 patients satisfied the inclusion criteria. Biopsy and RP Gleason score categories correlated exactly in 937 (69%) men. Gleason undergrading occurred in 361 (26%) men and overgrading in 65 (5%). The exact correlation of GS between biopsy and RP was 58%, 66%, and 75% in groups 1, 2, and 3, respectively. The most common discordant finding was undergrading of the biopsy specimen. The number of cases with exact correlation was highest in GS 7 (78%). Undergrading was more in GS 6 or less (35%) and overgrading was more in the GS 8 through 10 (35%) category. CONCLUSIONS This large, single institutional study confirms increasing concordance of Gleason scores in prostate needle biopsies and surgical specimens. This is reassuring for patients assessing various treatment options for prostate cancer.

Factors affecting erectile function after radical retropubic prostatectomy: results from 1620 consecutive patients.

To report the return of erectile function in 1620 consecutive men after radical retropubic prostatectomy (RRP), chosen by half of men diagnosed with clinically localized prostate cancer, and the goal of which is to completely excise the tumour while preserving continence and erectile function.

Long-term survival in patients undergoing radical nephrectomy and inferior vena cava thrombectomy: single-center experience.

BACKGROUND Renal cell carcinoma (RCC) with a tumor thrombus extension into the inferior vena cava (IVC) demands aggressive surgical management. OBJECTIVE To evaluate the long-term survival in patients undergoing radical nephrectomy and IVC thrombectomy. DESIGN, SETTING, AND PARTICIPANTS We performed a retrospective analysis of 87 patients undergoing surgery between 1997 and 2008. The patients were grouped according to the extent of tumor thrombus, with level I involving the IVC at the level of the renal vein, level II being infrahepatic IVC, level III being intrahepatic IVC, and level IV being suprahepatic IVC or right atrium. Relevant clinical and pathologic data were analyzed. MEASUREMENTS Disease-free survival (DFS) and disease-specific survival (DSS) were studied. RESULTS AND LIMITATIONS The median follow-up was 22 mo, and 19, 14, 40, and 14 patients had level I, II, III, and IV IVC thrombus, respectively. Among patients with M0 disease, 22 developed metastases. The 5-yr DFS was 64% for all levels and 74%, 69.5%, 59.5%, and 58% for levels I, II, III, and IV, respectively. Of the level I group, 16% of patients died of disease compared to 57% of the level IV group. The 5-yr DSS for all levels was 46% and 71%, 48%, 40%, and 35% for levels I, II, III, and IV, respectively. Patients with level IV thrombus had a significantly lower 5-yr DSS compared to level I (p=0.03). However, when analyzed in two groups-supradiaphragmatic and infradiaphragmatic-there was no significant difference in DSS (P=0.14). On univariate analysis, metastasis at presentation, non-clear-cell histology, lymph node metastases, and higher nuclear grade were statistically significant prognostic factors influencing DSS. Only higher nuclear grade (p=0.03), metastasis at presentation (p<0.01), and non-clear-cell histology (p=0.03) were independent prognostic factors on multivariate analysis. CONCLUSIONS Radical nephrectomy and IVC thrombectomy offer reasonable long-term survival. The level of tumor thrombus is not an independent prognostic factor. Distant metastasis at presentation, higher nuclear grade, and non-clear-clear cell histology are significant prognostic factors influencing DSS.

Lymphadenectomy at the time of robot‐assisted radical cystectomy: results from the International Robotic Cystectomy Consortium

What’s known on the subject? and What does the study add?