Sanoj Punnen

A multi-institutional prospective trial in the USA confirms that the 4Kscore accurately identifies men with high-grade prostate cancer.

BACKGROUND The 4Kscore combines measurement of four kallikreins in blood with clinical information as a measure of the probability of significant (Gleason ≥7) prostate cancer (PCa) before prostate biopsy. OBJECTIVE To perform the first prospective evaluation of the 4Kscore in predicting Gleason ≥7 PCa in the USA. DESIGN, SETTING, AND PARTICIPANTS Prospective enrollment of 1012 men scheduled for prostate biopsy, regardless of prostate-specific antigen level or clinical findings, was conducted at 26 US urology centers between October 2013 and April 2014. INTERVENTION The 4Kscore. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The primary outcome was Gleason ≥7 PCa on prostate biopsy. The area under the receiver operating characteristic curve, risk calibration, and decision curve analysis (DCA) were determined, along with comparisons of probability cutoffs for reducing the number of biopsies and their impact on delaying diagnosis. RESULTS AND LIMITATIONS Gleason ≥7 PCa was found in 231 (23%) of the 1012 patients. The 4Kscore showed excellent calibration and demonstrated higher discrimination (AUC 0.82) and net benefit compared to a modified Prostate Cancer Prevention Trial Risk Calculator 2.0 model and standard of care (biopsy for all men) according to DCA. A possible reduction of 30-58% in the number biopsies was identified with delayed diagnosis in only 1.3-4.7% of Gleason ≥7 PCa cases, depending on the threshold used for biopsy. Pathological assessment was performed according to the standard of care at each site without centralized review. CONCLUSION The 4Kscore showed excellent diagnostic performance in detecting significant PCa. It is a useful tool in selecting men who have significant disease and are most likely to benefit from a prostate biopsy from men with no cancer or indolent cancer. PATIENT SUMMARY The 4Kscore provides each patient with an accurate and personalized measure of the risk of Gleason ≥7 cancer to aid in decision-making regarding the need for prostate biopsy.

Management of Biochemical Recurrence After Primary Treatment of Prostate Cancer: A Systematic Review of the Literature

CONTEXT Despite excellent cancer control with the treatment of localized prostate cancer (PCa), some men will experience a recurrence of disease. The optimal management of recurrent disease remains uncertain. OBJECTIVE To systematically review recent literature regarding management of biochemical recurrence after primary treatment for localized PCa. EVIDENCE ACQUISITION A comprehensive systematic review of the literature was performed from 2000 to 2012 to identify articles pertaining to management after recurrent PCa. Search terms included prostate cancer recurrence, salvage therapy, radiorecurrent prostate cancer, post HIFU, post cryoablation, postradiation, and postprostatectomy salvage. Studies were selected according to Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines and required to provide a comprehensive description of primary and secondary treatments along with outcomes. EVIDENCE SYNTHESIS The data from 32 original publications were reviewed. The most common option for local salvage therapy after radical prostatectomy (RP) was radiation. Options for local salvage therapy after primary radiation included RP, brachytherapy, and cryotherapy. Different definitions of recurrence and risk profiles among patients make comparative assessment among salvage treatment modalities difficult. Triggers for intervention and factors predicting response to salvage therapy vary. CONCLUSIONS Radiation therapy (RT) after RP can provide durable prostate-specific antigen (PSA) responses in a sizeable percentage of men, especially when given early (ie, PSA <1 ng/ml). Though a few studies suggest improvements in mortality, prospective randomized trials are needed and underway. The role of salvage treatment after RT is less clear.

Long-term Health-related Quality of Life After Primary Treatment for Localized Prostate Cancer: Results from the CaPSURE Registry

BACKGROUND Few studies have reported on late declines and long-term health-related quality of life (HRQOL) after prostate cancer (PCa) treatment. OBJECTIVE We assessed long-term HRQOL following various treatments for localized PCa. DESIGN, SETTING, AND PARTICIPANTS This cohort study of HRQOL up to 10 yr after treatment used a prospectively accrued, nationwide PCa registry that collects longitudinal patient-reported HRQOL. INTERVENTION Various primary treatments for localized PCa. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The Medical Outcomes Studies 36-item Short Form and the University of California, Los Angeles, Prostate Cancer Index characterized physical function, mental health, and sexual, urinary, and bowel function and bother. Repeated measures mixed-model analysis assessed change in HRQOL by treatment over time, and logistic regression was used to measure the likelihood of a clinically significant decline in HRQOL. RESULTS AND LIMITATIONS Among 3294 men, 1139 (34%) underwent nerve-sparing radical prostatectomy (NSRP), 860 (26%) underwent non-NSRP, 684 (21%) underwent brachytherapy, 386 (12%) underwent external beam radiotherapy, 161 (5%) underwent primary androgen deprivation therapy, and 64 (2%) pursued watchful waiting/active surveillance. Median follow-up was 74 mo (interquartile range: 50-102). Most treatments resulted in early declines in HRQOL, with some recovery over the next 1-2 yr and a plateau in scores thereafter. Surgery had the largest impact on sexual function and bother and on urinary function, radiation had the strongest effect on bowel function, and androgen deprivation therapy had the strongest effect on physical function. The main limitation was attrition among the cohort. CONCLUSIONS Although most men experience initial declines in HRQOL in the first 2 yr after treatment, there is little change from 3 to 10 yr and most differences between treatments attenuated over time. PATIENT SUMMARY Various treatments for prostate cancer result in a distinct constellation of adverse effects on health-related quality of life, which may have a long-term impact. These findings are helpful regarding shared decision making over choice of primary treatment.

Multi-institutional Validation of the CAPRA-S Score to Predict Disease Recurrence and Mortality After Radical Prostatectomy

BACKGROUND The University of California, San Francisco, Cancer of the Prostate Risk Assessment Postsurgical (CAPRA-S) score uses pathologic data from radical prostatectomy (RP) to predict prostate cancer recurrence and mortality. However, this clinical tool has never been validated externally. OBJECTIVE To validate CAPRA-S in a large, multi-institutional, external database. DESIGN, SETTING, AND PARTICIPANTS The Shared Equal Access Regional Cancer Hospital (SEARCH) database consists of 2892 men who underwent RP from 2001 to 2011. With a median follow-up of 58 mo, 2670 men (92%) had complete data to calculate a CAPRA-S score. INTERVENTION RP. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The main outcome was biochemical recurrence. Performance of CAPRA-S in detecting recurrence was assessed and compared with a validated postoperative nomogram by concordance index (c-index), calibration plots, and decision curve analysis. Prediction of cancer-specific mortality was assessed by Kaplan-Meier analysis and the c-index. RESULTS AND LIMITATIONS The mean age was 62 yr (standard deviation: 6.3), and 34.3% of men had recurrence. The 5-yr progression-free probability for those patients with a CAPRA-S score of 0-2, 3-5, and 6-10 (defining low, intermediate, and high risk) was 72%, 39%, and 17%, respectively. The CAPRA-S c-index was 0.73 in this validation set, compared with a c-index of 0.72 for the Stephenson nomogram. Although CAPRA-S was optimistic in predicting the likelihood of being free of recurrence at 5 yr, it outperformed the Stephenson nomogram on both calibration plots and decision curve analysis. The c-index for predicting cancer-specific mortality was 0.85, with the caveat that this number is based on only 61 events. CONCLUSIONS In this external validation, the CAPRA-S score predicted recurrence and mortality after RP with a c-index >0.70. The score is an effective prognostic tool that may aid in determining the need for adjuvant therapy.

Androgen Deprivation Therapy and Cardiovascular Risk

PURPOSE The potential association between androgen deprivation therapy (ADT) and cardiovascular mortality (CVM) remains controversial. This study assessed mortality outcomes in a large national registry to further elucidate the association between treatment selection and cause of mortality. PATIENTS AND METHODS A total of 7,248 men in the CaPSURE registry were analyzed. Treatment was categorized as local only, primary ADT monotherapy, local treatment plus ADT, and watchful waiting/active surveillance (WW/AS). Competing hazards survival analysis was performed for prostate cancer-specific mortality (PCSM), CVM, and all-cause mortality. A propensity score-adjusted and a propensity-matched analysis were undertaken to adjust for imbalances in covariates among men receiving various treatments. RESULTS Patients treated with ADT or WW/AS had a higher likelihood of PCSM than those treated with local therapy alone. Patients treated with primary ADT had an almost two-fold greater likelihood of CVM (HR, 1.94; 95% CI, 1.29 to 2.97) than those treated with local therapy alone; however, patients treated with WW/AS had a greater than two-fold increased risk of CVM (HR, 2.46; 95% CI, 1.53 to 3.95). A propensity-matching algorithm in a subset of 1,391 patients was unable to find a significant difference in CVM between those who did or did not receive ADT. CONCLUSION Patients matched on propensity to receive ADT did not show an association between ADT and CVM. This suggests that potential unmeasured variables affecting treatment selection may confound the relationship between ADT use and cardiovascular risk. However, an association may yet exist, because the propensity score could not include all known risk factors for CVM.

A longitudinal study of anxiety, depression and distress as predictors of sexual and urinary quality of life in men with prostate cancer

To evaluate the prevalence of depression, anxiety and distress among active surveillance (AS) and radical prostatectomy (RP) patients. To evaluate the impact of these symptoms at baseline on urinary and sexual quality of life at follow‐up.

Utility of Incorporating Genetic Variants for the Early Detection of Prostate Cancer

Purpose: Several single nucleotide polymorphisms (SNP) have been associated with the risk of prostate cancer. The clinical utility of using SNPs in the early detection of prostate cancer has not been evaluated. Experimental Design: We examined a panel of 25 SNPs from candidate genes and chromosomal regions in 3,004 unselected men who were screened for prostate cancer using serum prostate-specific antigen (PSA) and digital rectal examination. All underwent a prostate biopsy. We evaluated the ability of these SNPs to help predict the presence of prostate cancer at biopsy. Results: Of the 3,004 patients, 1,389 (46.2%) were found to have prostate cancer. Fifteen of the 25 SNPs studied were significantly associated with prostate cancer (P = 0.02-7 × 10−8). We selected a combination of 4 SNPs with the best predictive value for further study. After adjusting for other predictive factors, the odds ratio for patients with all four of the variant genotypes compared with men with no variant genotype was 5.1 (95% confidence interval, 1.6-16.5; P = 0.006). When incorporated into a nomogram, genotype status contributed more significantly than PSA, family history, ethnicity, urinary symptoms, and digital rectal examination (area under the curve = 0.74). The positive predictive value of the PSA test ranged from 42% to 94% depending on the number of variant genotypes carried (P = 1 × 10−15). Conclusions: SNP genotyping can be used in a clinical setting for the early detection of prostate cancer in a nomogram approach and by improving the positive predictive value of the PSA test.

How does robot-assisted radical prostatectomy (RARP) compare with open surgery in men with high-risk prostate cancer?

Previous studies have shown that robot‐assisted radical prostatectomy (RARP) can be performed in men with high‐risk prostate cancer with similar outcomes to that of open surgery. However, most of the literature consists of small case series and compares RARP outcomes to open outcomes from the literature. This study compared a cohort of high‐risk patients undergoing open RP and RARP at a single institution with good follow up. We found no difference in positive margin rates or likelihood of prostate cancer recurrence. This adds to the growing evidence that RARP is a safe option for men with high‐risk disease.

Health-related quality of life from a prospective randomised clinical trial of robot-assisted laparoscopic vs open radical cystectomy

To compare health‐related quality‐of‐life (HRQoL) outcomes for robot‐assisted laparoscopic radical cystectomy (RARC) with those of traditional open radical cystectomy (ORC) in a prospective randomised fashion.

Men with Low Preoperative Sexual Function May Benefit from Nerve Sparing Radical Prostatectomy

PURPOSE We determined the effect of nerve sparing radical prostatectomy on sexual and urinary function in men at various levels of pretreatment sexual function. MATERIALS AND METHODS Men in the CaPSURE™ (Cancer of the Prostate Strategic Urologic Research Endeavor) database who underwent radical prostatectomy and had baseline and 2-year posttreatment UCLA-PCI sexual function and urinary function scores were selected. Nerve sparing was categorized as bilateral, unilateral or none and the level of pretreatment sexual function was divided into quartiles. The cohort was divided into subgroups of nerve sparing technique and pretreatment sexual function. Differences between sexual function and urinary function among subgroups were determined. A test of interaction was performed between preoperative sexual function and degree of nerve sparing on postoperative sexual function and urinary function scores. RESULTS A total of 1,322 patients met the study inclusion criteria. Median patient age was 61 years (range 41 to 79). Bilateral, unilateral and no nerve sparing procedures were performed in 899, 200 and 223 men, respectively. The effects of nerve sparing on sexual function differed among the quartiles of preoperative sexual function (p <0.01). Nerve sparing did not have an effect on the sexual function of men in the lowest quartile of preoperative sexual function score (p = 0.15) but did have a significant beneficial effect on sexual function in the higher 3 quartiles (p = 0.04, p <0.01 and p <0.01, respectively). Alternatively, nerve sparing improved urinary function in men in the lowest quartile of baseline sexual function. CONCLUSIONS Nerve sparing radical prostatectomy results in better sexual function outcomes than no nerve sparing in most men except those with little baseline function. Urinary function was positively impacted in all men. Men who are suitable candidates for nerve preservation may benefit from nerve sparing surgery. Poorer baseline sexual function should not exclude these men from such surgery.