Updates to Advanced Prostate Cancer: AUA/SUO Guideline (2023).

PURPOSE: In 2022 the American Urological Association (AUA) requested an Update Literature Review (ULR) to incorporate new evidence generated since the 2020 publication of this guideline. The resulting 2023 Guideline Amendment addresses updated recommendations for patients with advanced prostate cancer. MATERIALS AND METHODS: The ULR addressed 23 of the original 38 guideline statements and included an abstract-level review of eligible studies published since the 2020 systematic review. Sixteen studies were selected for full text review. The current summary presents the updates made to the Guideline as a result of that new literature. RESULTS: The Advanced Prostate Cancer Panel amended evidence- and consensus-based statements based on an updated review to aid clinicians in the management of patients with advanced prostate cancer. These statements are detailed herein. CONCLUSION: This Guideline Amendment provides a framework designed to improve a clinician's ability to treat patients diagnosed with advanced prostate cancer with the most current evidence-based information. Further research and publication of high-quality clinical trials will be essential to continue to improve the quality of care for these patients.

Decision fatigue in low-value prostate cancer screening.

BACKGROUND: Low-value prostate-specific antigen (PSA) testing is common yet contributes substantial waste and downstream patient harm. Decision fatigue may represent an actionable target to reduce low-value urologic care. The objective of this study was to determine whether low-value PSA testing patterns by outpatient clinicians are consistent with decision fatigue. METHODS: Outpatient appointments for adult men without prostate cancer were identified at a large academic health system from 2011 through 2018. The authors assessed the association of appointment time with the likelihood of PSA testing, stratified by patient age and appropriateness of testing based on clinical guidelines. Appointments included those scheduled between 8:00 am and 4:59 pm, with noon omitted. Urologists were examined separately from other clinicians. RESULTS: In 1,581,826 outpatient appointments identified, the median patient age was 54 years (interquartile range, 37-66 years), 1,256,152 participants (79.4%) were White, and 133,693 (8.5%) had family history of prostate cancer. PSA testing would have been appropriate in 36.8% of appointments. Clinicians ordered testing in 3.6% of appropriate appointments and in 1.8% of low-value appointments. Appropriate testing was most likely at 8:00 am (reference group). PSA testing declined through 11:00 am (odds ratio [OR], 0.57; 95% CI, 0.50-0.64) and remained depressed through 4:00 pm (P < .001). Low-value testing was overall less likely (P < .001) and followed a similar trend, declining steadily from 8:00 am (OR, 0.48; 95% CI, 0.42-0.56) through 4:00 pm (P < .001; OR, 0.23; 95% CI, 0.18-0.30). Testing patterns in urologists were noticeably different. CONCLUSIONS: Among most clinicians, outpatient PSA testing behaviors appear to be consistent with decision fatigue. These findings establish decision fatigue as a promising, actionable target for reducing wasteful and low-value practices in routine urologic care. LAY SUMMARY: Decision fatigue causes poorer choices to be made with repetitive decision making. This study used medical records to investigate whether decision fatigue influenced clinicians' likelihood of ordering a low-value screening test (prostate-specific antigen [PSA]) for prostate cancer. In more than 1.5 million outpatient appointments by adult men without prostate cancer, the chances of both appropriate and low-value PSA testing declined as the clinic day progressed, with a larger decline for appropriate testing. Testing patterns in urologists were different from those reported by other clinicians. The authors conclude that outpatient PSA testing behaviors appear to be consistent with decision fatigue among most clinicians, and interventions may reduce wasteful testing and downstream patient harms.

Advanced Prostate Cancer: AUA/ASTRO/SUO Guideline PART II.

PURPOSE: The summary presented herein represents Part II of the two-part series dedicated to Advanced Prostate Cancer: AUA/ASTRO/SUO Guideline discussing prognostic and treatment recommendations for patients with castration-resistant disease. Please refer to Part I for discussion of the management of patients with biochemical recurrence without metastatic disease after exhaustion of local treatment options as well as those with metastatic hormone-sensitive prostate cancer. RESULTS: The Advanced Prostate Cancer Panel created evidence- and consensus-based guideline statements to aid clinicians in the management of patients with advanced prostate cancer. Such statements are summarized in figure 1[Figure: see text] and detailed herein. MATERIALS AND METHODS: The systematic review utilized to inform this guideline was conducted by an independent methodological consultant. A research librarian conducted searches in Ovid MEDLINE (1998 to January Week 5 2019), Cochrane Central Register of Controlled Trials (through December 2018), and Cochrane Database of Systematic Reviews (2005 through February 6, 2019). An updated search was conducted prior to publication through January 20, 2020. The methodology team supplemented searches of electronic databases with the studies included in the prior AUA review and by reviewing reference lists of relevant articles. CONCLUSIONS: This guideline attempts to improve a clinician's ability to treat patients diagnosed with advanced prostate cancer. Continued research and publication of high-quality evidence from future trials will be essential to improve the level of care for these patients.

Advanced Prostate Cancer: AUA/ASTRO/SUO Guideline PART I.

PURPOSE: The summary presented herein represents Part I of the two-part series dedicated to Advanced Prostate Cancer: AUA/ASTRO/SUO Guideline discussing prognostic and treatment recommendations for patients with biochemical recurrence without metastatic disease after exhaustion of local treatment options as well as those with metastatic hormone-sensitive prostate cancer. Please refer to Part II for discussion of the management of castration-resistant disease. MATERIALS AND METHODS: The systematic review utilized to inform this guideline was conducted by an independent methodological consultant. A research librarian conducted searches in Ovid MEDLINE (1998 to January Week 5 2019), Cochrane Central Register of Controlled Trials (through December 2018), and Cochrane Database of Systematic Reviews (2005 through February 6, 2019). An updated search was conducted prior to publication through January 20, 2020. The methodology team supplemented searches of electronic databases with the studies included in the prior AUA review and by reviewing reference lists of relevant articles. RESULTS: The Advanced Prostate Cancer Panel created evidence- and consensus-based guideline statements to aid clinicians in the management of patients with advanced prostate cancer. Such statements are summarized in figure 1[Figure: see text] and detailed herein. CONCLUSIONS: This guideline attempts to improve a clinician's ability to treat patients diagnosed with advanced prostate cancer. Continued research and publication of high-quality evidence from future trials will be essential to improve the level of care for these patients.

The Relative Importance of Race Compared to Health Care and Social Factors in Predicting Prostate Cancer Mortality: A Random Forest Approach.

PURPOSE: There is a differential in prostate cancer mortality between black and white men. Advances in precision medicine have shifted the research focus toward underlying genetic differences. However, nonbiological factors may have a large role in these observed disparities. Therefore, we sought to measure the relative importance of race compared to health care and social factors on prostate cancer specific mortality. MATERIALS AND METHODS: Using the SEER (Surveillance, Epidemiology, and End Results) database we identified 514,878 men diagnosed with prostate cancer at age 40 years or greater between 2004 and 2012. We also selected a subset of black and white men matched by age, stage and birth year. We stratified patients by age 40 to 54, 55 to 69 and 70 years or older and disease stage, resulting in 18 groups. By applying random forest methods with variable importance measures we analyzed 15 variables and interactions across 4 categories of factors (tumor characteristics, race, and health care and social factors) and the relative importance for prostate cancer specific mortality. RESULTS: Tumor characteristics at diagnosis were the most important factors for prostate cancer mortality. Across all groups race was less than 5% as important as tumor characteristics and only more important than health care and social factors in 2 of the 18 groups. Although race had a significant impact, health care and social factors known to be associated with racial disparities had greater or similarly important effects across all ages and stages. CONCLUSIONS: Eradicating disparities in prostate cancer survival will require a multipronged approach, including advances in precision medicine. Disparities will persist unless health care access and social equality are achieved among all populations.

Modulation of Premetastatic Niche by the Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitor Pazopanib in Localized High-Risk Prostate Cancer Followed by Radical Prostatectomy: A Phase II Randomized Trial.

LESSONS LEARNED: Pazopanib was not effective in altering the premetastatic niche in the neoadjuvant setting.Pazopanib was safe and well tolerated without any new safety signals. BACKGROUND: Vascular endothelial growth factor receptor 1 (VEGFR1) expressing myeloid-derived suppressor cells (VEGFR1+ MDSCs) potentially foster metastases by establishing a premetastatic niche. In a preclinical study, VEGFR1+ clustering in lymph nodes (LNs) independently predicted time to biochemical recurrence (TTBR) in localized prostate cancer [1]. The hypothesis was that neoadjuvant pazopanib therapy will decrease VEGFR1+ clusters in pelvic lymph nodes and improve outcomes. METHODS: This is a phase II trial (NCT01832259) of neoadjuvant pazopanib 800 mg versus placebo daily for 4 weeks in high-risk localized prostate cancer. The primary endpoint was a decrease in VEGFR1+ MDSC clustering assessed by immunohistochemistry (IHC) analysis. Secondary endpoints were safety, feasibility, and TTBR. RESULTS: Thirty patients were randomized to pazopanib versus placebo, with 15 patients randomized to each arm. Demographic and disease characteristics were similar in both arms. There was no difference in the VEGFR1+ clustering between the treatment arms (p = .345). Neoadjuvant therapy with pazopanib was well tolerated, and surgical complications were similar in both arms. CONCLUSION: Neoadjuvant pazopanib therapy did not alter the premetastatic niche; however, treatment targeting vascular endothelial growth factor (VEGF) in the preoperative period was safe and feasible, which may open up the avenue to investigate novel combinatorial regimens, including a VEGF inhibitor in combination with immune checkpoint inhibitor in this setting.

Castration-Resistant Prostate Cancer: AUA Guideline Amendment 2018.

PURPOSE: The purpose of this amendment is to incorporate newly-published literature to provide a rational basis for the management of patients with non-metastatic castration-resistant prostate cancer (CRPC). MATERIALS AND METHODS: The original systematic review and meta-analysis of the published literature yielded 303 studies published from 1996 through 2013. This review informed the majority of the guideline statements from the 2013 guideline. Clinical Principles and Expert Opinions were used for guideline statements lacking sufficient evidence. The guideline was subsequently amended in April 2014 and March 2015. The current 2018 amendment search yielded 770 references with 47 studies eventually providing relevant data. The resulting amendment focuses on the incorporation of information relating to the treatment of patients with non-metastatic CRPC. RESULTS: Guideline statements based on six Index Patients developed to represent the most common scenarios encountered in clinical practice were amended appropriately. The additional literature provided the basis for an update of current supporting text as well as the incorporation of new guideline statements for asymptomatic non-metastatic CRPC. CONCLUSIONS: Given the rapidly evolving nature of this field, this guideline should be used in conjunction with recent systematic literature reviews and an understanding of individual patients' treatment goals. Shared decision-making incorporating patients' preferences and personal goals should be implemented when choosing management strategies. This guideline will be continually updated as new literature emerges.

Decipher test impacts decision making among patients considering adjuvant and salvage treatment after radical prostatectomy: Interim results from the Multicenter Prospective PRO-IMPACT study.

BACKGROUND: Patients with prostate cancer and their providers face uncertainty as they consider adjuvant radiotherapy (ART) or salvage radiotherapy (SRT) after undergoing radical prostatectomy. The authors prospectively evaluated the impact of the Decipher test, which predicts metastasis risk after radical prostatectomy, on decision making for ART and SRT. METHODS: A total of 150 patients who were considering ART and 115 who were considering SRT were enrolled. Providers submitted a management recommendation before processing the Decipher test and again at the time of receipt of the test results. Patients completed validated surveys on prostate cancer (PCa)-specific decisional effectiveness and PCa-related anxiety. RESULTS: Before the Decipher test, observation was recommended for 89% of patients considering ART and 58% of patients considering SRT. After Decipher testing, 18% (95% confidence interval [95% CI], 12%-25%) of treatment recommendations changed in the ART arm, including 31% among high-risk patients; and 32% (95% CI, 24%-42%) of management recommendations changed in the salvage arm, including 56% among high-risk patients. Decisional Conflict Scale (DCS) scores were better after viewing Decipher test results (ART arm: median DCS before Decipher, 25 and after Decipher, 19 [P<.001]; SRT arm: median DCS before Decipher, 27 and after Decipher, 23 [P<.001]). PCa-specific anxiety changed after Decipher testing; fear of PCa disease recurrence in the ART arm (P = .02) and PCa-specific anxiety in the SRT arm (P = .05) decreased significantly among low-risk patients. Decipher results reported per 5% increase in 5-year metastasis probability were associated with the decision to pursue ART (odds ratio, 1.48; 95% CI, 1.19-1.85) and SRT (odds ratio, 1.41; 95% CI, 1.09-1.81) in multivariable logistic regression analysis. CONCLUSIONS: Knowledge of Decipher test results was associated with treatment decision making and improved decisional effectiveness among men with PCa who were considering ART and SRT. Cancer 2017;123:2850-59. © 2017 American Cancer Society.

Childhood Cancer Risk in the Siblings and Cousins of Men with Poor Semen Quality.

PURPOSE: Poor semen quality is associated with reduced somatic health and increased cancer risk. Infertility and cancer are increasingly being linked by epidemiologists and basic scientists. We sought to identify semen parameters associated with an increased childhood cancer risk in the family members of subfertile men. MATERIALS AND METHODS: We performed a retrospective cohort study in men from the SHARE (Subfertility Heath and Assisted Reproduction) study who underwent semen analysis between 1994 and 2011. We used fertile population controls from the Utah Population Data Base. Our primary outcome was the risk of any childhood (18 years or younger) cancer in the siblings and cousins of men who underwent semen analysis compared to fertile, age matched controls. Cox proportional hazard regression models were used to test the association between semen quality and childhood cancer incidence. RESULTS: We selected 10,511 men with complete semen analysis and an equal number of fertile controls. These men had a total of 63,891 siblings and 327,753 cousins. A total of 170 and 958 childhood cancers were identified in siblings and cousins, respectively. The 3 most common cancers diagnosed in siblings were acute lymphoblastic leukemia in 37, brain cancer in 35 and Hodgkin lymphoma in 15. Oligozoospermia was associated with a twofold increased risk of any childhood cancer and a threefold increased risk of acute lymphoblastic leukemia in the siblings of subfertile men compared to fertile controls (HR 2.09, 95% CI 1.18-3.69 vs HR 3.07, 95% CI 1.11-8.46). CONCLUSIONS: Siblings of men with oligozoospermia are at increased risk for any-site cancer and acute lymphoblastic leukemia. This suggests a shared genetic/epigenetic insult or an environmental exposure that merits further investigation.

Risk of childhood mortality in family members of men with poor semen quality.

STUDY QUESTION: What is the familial childhood mortality in first-degree (FDR) and second-degree relatives (SDR) of patients undergoing semen analysis (SA)? SUMMARY ANSWER: The relationship between infertility and congenital malformations (CM) in offspring is complex, with an increased risk of death due to CM in FDR, but not SDR, of men with lower semen parameters. WHAT IS KNOWN ALREADY: Semen quality is an established predictor of men's somatic health. We can gain a better understanding of possible genetic or environmental determinants of the infertility phenotype by exploring familial aggregation of childhood mortality in relatives of men with poor semen quality. STUDY DESIGN, SIZE, DURATION: Retrospective cohort study from the Subfertility, Health and Assisted Reproduction study (cohort compiled 1996-2011) linked with patient/familial information from the Utah Population Database (UPDB). Index cases included a clinic-referred sample of 12 889 men who underwent SA and had adequate familial and follow-up data in the UPDB. Parameters of semen quality included: semen concentration, sperm count, motility, total motile count, sperm head morphology, sperm tail morphology and vitality. PARTICIPANTS/MATERIALS, SETTING, METHODS: SA data were collected from two tertiary medical center andrology laboratories that have captured ~90% of all SA performed in Utah since 2004. Age- and sex-matched fertile controls were selected to create the comparison group for determining risk of childhood death (to age 20 years) in family members. A total of 79 750 siblings and 160 016 aunts/uncles were used to investigate the familial aggregation of childhood mortality. The main outcome was childhood mortality in FDR and SDR of men with SA and their matched controls. All-cause and cause-specific Cox proportional hazard models were used to test the association between semen quality and childhood mortality in family members. Cause-specific models were considered for cancer and CM. MAIN RESULTS AND THE ROLE OF CHANCE: In the cohort of men with SA, there were 406 (1.0%) deaths in FDR and 772 (1.1%) deaths in SDR due to any cause. There was no significant difference in the risk of all-cause childhood mortality between the relatives of men with SA and the fertile control group [hazard ratio (HR)Female = 1.08, 95% CI = 0.88, 1.32; HRMale = 0.88, 95% CI = 0.75, 1.04]. We found no association between semen quality and risk for childhood cancer mortality in FDR or SDR (HRFDR = 0.98, 95% CI = 0.62, 1.54; HRSDR = 1.12, 95% CI = 0.83, 1.50). The FDR of men with SA and fertile controls were followed on average for 19.71 and 19.73 years, respectively. During this period of follow-up, FDR of men with SA had an unadjusted 40% relative risk of increased CM-related death. After stratifying by semen parameters and adjusting for birth year, we found FDR of men with worse semen quality, and notably azoospermic men (HR = 2.69, 95% CI = 1.24,5.84), were at higher risk of CM-related death. LIMITATIONS REASONS FOR CAUTION: A large proportion of men with SA in the study had normal semen parameters. It is important to note that these men themselves may not be subfertile, but they were subfertile at the couple level (i.e. the female partner may be infertile). In addition, care is needed when interpreting our results, as we do not have semen measures on our sample of fertile men. Second, we were unable to include potential confounders such as medical comorbidities, smoking status, or environmental exposures. Third, men with SA were seen at the University of Utah or Intermountain Health Care clinics for a fertility evaluation thereby suggesting a more select population. Fourth, we chose to categorize morphology into equally distributed quartiles as a response to the fact that the World Health Organization threshold for normal motility changed multiple times during our study period. Lastly, we do not know the proportion of female partners with diagnosed infertility. We chose not to subcategorize each infertile male by infertile diagnosis because our goal was to understand how semen parameters influenced familial childhood mortality. WIDER IMPLICATIONS OF THE FINDINGS: We are not the first study to show a relationship between fertility and CMs. Children conceived through ART may be at higher risk of birth defects, however it is not known if the relationship is causal or if there is some underlying factor linking infertility and birth outcomes. This study provides further evidence that the increased risk of congenital birth defects may not be due to the ART, but rather genetic or environmental factors that link the two outcomes. We encourage further research in order to confirm a relationship between semen quality and increased risk for CM. STUDY FUNDING/COMPETING INTERESTS: This work was supported by the National Institutes of Health - National Institute of Aging [Grant numbers 1R21AG036938-01, 2R01 AG022095 and 1K12HD085852-01]. Authors have no competing interests to disclose. TRIAL REGISTRATION NUMBER: Not applicable.

Management of Radiation Therapy Oncology Group grade 4 urinary adverse events after radiotherapy for prostate cancer.

OBJECTIVE: To describe the management of Radiation Therapy Oncology Group (RTOG) grade 4 urinary adverse events (UAEs) after radiotherapy (RT) for prostate cancer (PCa). METHODS: We conducted a single-centre retrospective review, over a 6-year period (2010-2015), to identify men with RTOG grade 4 UAEs after RT for PCa. RT was classified as combined therapy (radical prostatectomy [RP] followed by external beam radiotherapy [EBRT], EBRT + low-dose-rate [LDR] brachytherapy, EBRT + high-dose-rate [HDR] brachytherapy or other combinations of RT) or monotherapy RT. UAEs were classified as outlet (urethral stricture, bladder neck contracture, prostate necrosis, or recto-urethral fistula) or bladder (contraction, necrosis, fistula, ureteric stricture or haemorrhage) UAEs. RESULTS: We identified 73 men with a mean age of 73 years. Of these, 44 (60%) received combined therapy, consisting of RP + EBRT (n = 19), HDR brachytherapy + EBRT (n = 19), LDR brachytherapy + EBRT (n = 5), and other combined RT (n = 1). Twenty-nine (40%) patients had monotherapy consisting of EBRT (n = 4), HDR brachytherapy (n = 11), LDR brachytherapy (n = 12), or proton beam therapy (n = 2). UAEs were isolated to the bladder in six men (8%), the outlet in 52 men (71%), and to both in 15 men (21%). UAE management included: conservative in 21 (29%), indwelling catheters in 12 (16%), reconstructive in 19 (26%), and urinary diversion (UD) in 23 men (32%). Reconstruction included: ureteric (n = 4), recto-urethral fistula repair (n = 2), and posterior urethroplasty (n =13), of which 14/16 surgeries (88%) with follow-up >90 days were successful. CONCLUSIONS: Although the incidence of RTOG grade 4 UAEs after PCa radiation treatment is not well defined, their associated morbidity is significant, and approximately one third of patients with these high-grade complications require UD. Conversely, only about a quarter of patients can be managed with conservative strategies or local surgeries. Reconstruction is successful in selected patients.

Castration-Resistant Prostate Cancer: AUA Guideline Amendment 2015.

PURPOSE: The purpose of this amendment is to incorporate relevant newly-published literature to better provide a rational basis for the management of patients with castration-resistant prostate cancer. MATERIALS AND METHODS: The original systematic review and meta-analysis of the published literature yielded 303 studies published from 1996 through 2013. This review informed the majority of the guideline statements. Clinical Principles and Expert Opinions were used for guideline statements lacking sufficient evidence. In April 2014, the CRPC guideline underwent amendment based on an additional literature search, which retrieved additional studies published between February 2013 and February 2014. Thirty-seven studies from this search provided data relevant to the specific treatment modalities for CRPC. In March 2015, the CRPC guideline underwent a second amendment, which incorporated 10 additional studies into the evidence base published through February 2015. RESULTS: Guideline statements based on six index patients developed to represent the most common scenarios encountered in clinical practice were amended appropriately. The additional literature provided the basis for an update of current supporting text as well as the incorporation of new guideline statements for multiple index patients. CONCLUSIONS: Given the rapidly evolving nature of this field, this guideline should be used in conjunction with recent systematic literature reviews and an understanding of the individual patient's treatment goals. Patients' preferences and personal goals should be considered when choosing management strategies. This guideline will be continually updated as new literature emerges in the field.

A 10-Item Checklist Improves Reporting of Critical Procedural Elements during Transurethral Resection of Bladder Tumor.

PURPOSE: Previous studies have demonstrated significant variation in recurrence rates after transurethral resection of bladder tumor, likely due to differences in surgical quality. We sought to create a framework to define, measure and improve the quality of transurethral resection of bladder tumor using a surgical checklist. MATERIALS AND METHODS: We formed a multi-institutional group of urologists with expertise with bladder cancer and identified 10 critical items that should be performed during every high quality transurethral bladder tumor resection. We prospectively implemented a 10-item checklist into practice and reviewed the operative reports of such resections performed before and after implementation. Results at all institutions were combined in a meta-analysis to estimate the overall change in the mean number of items documented. RESULTS: The operative notes for 325 transurethral bladder tumor resections during checklist use were compared to those for 428 performed before checklist implementation. Checklist use increased the mean number of items reported from 4.8 to 8.0 per resection, resulting in a mean increase of 3.3 items (95% CI 1.9-4.7) on meta-analysis. With the checklist the percentage of reports that included all 10 items increased from 0.5% to 27% (p <0.0001). Surgeons who reported more checklist items tended to have a slightly higher proportion of biopsies containing muscle, although not at conventional significance (p = 0.062). CONCLUSIONS: The use of a 10-item checklist during transurethral resection of bladder tumor improved the reporting of critical procedural elements. Although there was no clear impact on the inclusion of muscle in the specimen, checklist use may enhance surgeon attention to important aspects of the procedure and be a lever for quality improvement.

NCCN Guidelines Insights: Prostate Cancer Early Detection, Version 2.2016.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Prostate Cancer Early Detection provide recommendations for prostate cancer screening in healthy men who have elected to participate in an early detection program. The NCCN Guidelines focus on minimizing unnecessary procedures and limiting the detection of indolent disease. These NCCN Guidelines Insights summarize the NCCN Prostate Cancer Early Detection Panel's most significant discussions for the 2016 guideline update, which included issues surrounding screening in high-risk populations (ie, African Americans, BRCA1/2 mutation carriers), approaches to refine patient selection for initial and repeat biopsies, and approaches to improve biopsy specificity.

Testicular Microlithiasis: What Should You Recommend?

OBJECTIVE: Ultrasound surveillance of patients with testicular microlithiasis (TM) has been recommended because of the reported association between TM and testicular cancer (TC). The purpose of this review is to summarize what is known about TM and discuss recent recommendations. CONCLUSION: The most recent recommendations do not support the use of routine ultrasound surveillance for patients with TM who are at low risk for TC. A template for possible use in reporting TM is also provided.

Prostate cancer risk prediction based on complete prostate cancer family history.

BACKGROUND: Prostate cancer (PC) relative risks (RRs) are typically estimated based on status of close relatives or presence of any affected relatives. This study provides RR estimates using extensive and specific PC family history. METHODS: A retrospective population-based study was undertaken to estimate RRs for PC based on complete family history of PC. A total of 635,443 males, all with ancestral genealogy data, were analyzed. RRs for PC were determined based upon PC rates estimated from males with no PC family history (without PC in first, second, or third degree relatives). RRs were determined for a variety of constellations, for example, number of first through third degree relatives; named (grandfather, father, uncle, cousins, brothers); maternal, paternal relationships, and age of onset. RESULTS: In the 635,443 males analyzed, 18,105 had PC. First-degree RRs ranged from 2.46 (=1 first-degree relative affected, CI = 2.39-2.53) to 7.65 (=4 first-degree relatives affected, CI = 6.28-9.23). Second-degree RRs for probands with 0 affected first-degree relatives ranged from 1.51 (≥1 second-degree relative affected, CI = 1.47-1.56) to 3.09 (≥5 second-degree relatives affected, CI = 2.32-4.03). Third-degree RRs with 0 affected first- and 0 affected second-degree relatives ranged from 1.15 (≥1 affected third-degree relative, CI = 1.12-1.19) to 1.50 (≥5 affected third-degree relatives, CI = 1.35-1.66). RRs based on age at diagnosis were higher for earlier age at diagnoses; for example, RR = 5.54 for ≥1 first-degree relative diagnosed before age 50 years (CI = 1.12-1.19) and RR = 1.78 for >1 second-degree relative diagnosed before age 50 years, CI = 1.33, 2.33. RRs for equivalent maternal versus paternal family history were not significantly different. CONCLUSIONS: A more complete PC family history using close and distant relatives and age at diagnosis results in a wider range of estimates of individual RR that are potentially more accurate than RRs estimated from summary family history. The presence of PC in second- and even third-degree relatives contributes significantly to risk. Maternal family history is just as significant as paternal family history. PC RRs based on a proband's complete constellation of affected relatives will allow patients and care providers to make more informed screening, monitoring, and treatment decisions.

Castration-resistant prostate cancer: AUA guideline amendment.

PURPOSE: The purpose of this amendment is to incorporate relevant newly-published literature to better provide a rational basis for the management of patients with castration-resistant prostate cancer. MATERIALS AND METHODS: The original systematic review and meta-analysis of the published literature yielded 303 articles published from 1996 through 2013. This review formed a majority of the guideline statements. Clinical Principles and Expert Opinions were used for guideline statements lacking sufficient evidence-based data. In April 2014, the CRPC guideline underwent amendment based on a second comprehensive literature search, which retrieved additional studies published between February 2013 and February 2014. Thirty-seven studies from this search provided data relevant to the specific treatment modalities for CRPC. RESULTS: Guideline statements based on six index patients developed to represent the most common scenarios encountered in clinical practice were amended appropriately. The additional literature provided the basis for an update of current supporting text as well as the incorporation of new guideline statements. Specifically, the addition of Radium-223 was placed in the guidelines related to the treatment of CRPC. CONCLUSIONS: Given the rapidly evolving nature of this field, this guideline should be used in conjunction with recent systematic literature reviews and an understanding of the individual patient's treatment goals. Patients' preferences and personal goals should be considered when choosing management strategies. The newly incorporated evidence-based statements supplement the original guideline published in 2013, which provided guidance for the treatment of men with CRPC. This guideline will be continually updated as new literature emerges in the field.

Long-term survival rates after resection for locally advanced kidney cancer: Memorial Sloan Kettering Cancer Center 1989 to 2012 experience.

PURPOSE: We analyzed the 23-year Memorial Sloan Kettering Cancer Center experience with surgical resection, and concurrent adrenalectomy and lymphadenectomy for locally advanced nonmetastatic renal cell carcinoma. MATERIALS AND METHODS: We retrospectively reviewed the records of 802 patients who underwent nephrectomy with or without concurrent adrenalectomy or lymphadenectomy for locally advanced renal cell carcinoma, defined as stage T3 or greater and M0. Patients who received adjuvant treatment within 3 months of surgery or had fewer than 3 months of followup or bilateral renal masses at presentation were excluded from analysis. Five and 10-year progression-free and overall survival was estimated by the Kaplan-Meier method. Differences between groups were analyzed by the log rank test. RESULTS: A total of 596 (74%) and 206 patients (26%) underwent radical and partial nephrectomy, respectively. Renal cell carcinoma progressed in 189 patients and 104 died of the disease. Median followup in patients without progression was 4.6 years. Symptoms at presentation, ASA(®) classification, tumor stage, histological subtype, grade and lymph node status were significantly associated with progression-free and overall survival. On multivariate analysis adrenalectomy use decreased with time but lymphadenectomy use increased (OR 0.82 vs 1.16 per year). Larger tumors were associated with a higher likelihood of concurrent adrenalectomy and lymphadenectomy. CONCLUSIONS: In our series of patients with locally advanced nonmetastatic renal cell carcinoma survival was favorable in those in good health who were asymptomatic at presentation with T3 tumors and negative lymph nodes. Further, there has been a trend toward more selective use of adrenalectomy and increased use of lymphadenectomy.

Gleason 6 Prostate Cancer: Translating Biology into Population Health.

PURPOSE: Gleason 6 (3+3) is the most commonly diagnosed prostate cancer among men with prostate specific antigen screening, the most histologically well differentiated and is associated with the most favorable prognosis. Despite its prevalence, considerable debate exists regarding the genetic features, clinical significance, natural history, metastatic potential and optimal management. MATERIALS AND METHODS: Members of the Young Urologic Oncologists in the Society of Urologic Oncology cooperated in a comprehensive search of the peer reviewed English medical literature on Gleason 6 prostate cancer, specifically focusing on the history of the Gleason scoring system, histological features, clinical characteristics, practice patterns and outcomes. RESULTS: The Gleason scoring system was devised in the early 1960s, widely adopted by 1987 and revised in 2005 with a more restrictive definition of Gleason 6 disease. There is near consensus that Gleason 6 meets pathological definitions of cancer, but controversy about whether it meets commonly accepted molecular and genetic criteria of cancer. Multiple clinical series suggest that the metastatic potential of contemporary Gleason 6 disease is negligible but not zero. Population based studies in the U.S. suggest that more than 90% of men newly diagnosed with prostate cancer undergo treatment and are exposed to the risk of morbidity for a cancer unlikely to cause symptoms or decrease life expectancy. Efforts have been proposed to minimize the number of men diagnosed with or treated for Gleason 6 prostate cancer. These include modifications to prostate specific antigen based screening strategies such as targeting high risk populations, decreasing the frequency of screening, recommending screening cessation, incorporating remaining life expectancy estimates, using shared decision making and novel biomarkers, and eliminating prostate specific antigen screening entirely. Large nonrandomized and randomized studies have shown that active surveillance is an effective management strategy for men with Gleason 6 disease. Active surveillance dramatically reduces the number of men undergoing treatment without apparent compromise of cancer related outcomes. CONCLUSIONS: The definition and clinical relevance of Gleason 6 prostate cancer have changed substantially since its introduction nearly 50 years ago. A high proportion of screen detected cancers are Gleason 6 and the metastatic potential is negligible. Dramatically reducing the diagnosis and treatment of Gleason 6 disease is likely to have a favorable impact on the net benefit of prostate cancer screening.

NCCN Clinical Practice Guidelines Prostate Cancer Early Detection, Version 2.2015.

Prostate cancer represents a spectrum of disease that ranges from nonaggressive, slow-growing disease that may not require treatment to aggressive, fast-growing disease that does. The NCCN Guidelines for Prostate Cancer Early Detection provide a set of sequential recommendations detailing a screening and evaluation strategy for maximizing the detection of prostate cancer that is potentially curable and that, if left undetected, represents a risk to the patient. The guidelines were developed for healthy men who have elected to participate in the early detection of prostate cancer, and they focus on minimizing unnecessary procedures and limiting the detection of indolent disease.