25-year perspective on prostate cancer: Conquering frontiers and understanding tumor biology.

Major changes in the field of prostate cancer over the last 25 years include the implementation of prostate specific antigen screening and the recognition that BRCA confers hereditary risk of prostate cancer. Quality of life and survivorship have driven risk stratification for localized prostate cancer, facilitated by molecular signatures and leading to increased acceptance of active surveillance as a mainstream treatment option. Advances in technology have improved efficacy and reduced toxicity in both radical prostatectomy and radiation therapy for localized prostate cancer. Improved understanding of the androgen receptor has yielded substantially more effective therapies. Future growth areas include personalized treatment based on genomic and genetic information, theranostics radiopharmaceuticals, and more aggressive treatment of metastatic disease to include focal therapy. Multidisciplinary management between specialized urologists, radiation oncologists, and medical oncologists remains central to maximizing patient outcomes.

A 25-year perspective on evaluation and understanding of biomarkers in urologic cancers.

The past 25 years have witnessed an explosion of investigative attempts to identify clinically useful biomarkers which can have meaningful impacts for patients with urologic cancers. However, in spite of the enormous amount of research aiming to identify markers with the hope of impacting patient care, only a handful have proven to have true clinical utility. Improvements in targeted imaging, pan-omics evaluation, and genetic sequencing at the tissue and single-cell levels have yielded many potential targets for continued biomarker investigation. This article, as one in this series for the 25th Anniversary Issue of Urologic Oncology: Seminars and Original Investigations, serves to give a perspective on our progress and failures over the past quarter-century in our highest volume urologic cancers: prostate, bladder, and kidney cancers.

Historical Considerations and Surgical Quality Improvement in Robotic Prostatectomy.

Laparoscopic prostatectomy was technically challenging and not widely adopted. Robotics led to the widespread adoption of minimally invasive prostatectomy, which has been used heavily, supplanting the open and traditional laparoscopic approach. The benefits of robotic prostatectomy are disputed. Data suggest that robotic prostatectomy outcomes have improved over time.

Considering the role of radical prostatectomy in 21st century prostate cancer care.

The practice of radical prostatectomy for treating prostate cancer has evolved remarkably since its general introduction around 1900. Initially described using a perineal approach, the procedure was later popularized using a retropubic one, after it was first described as such in 1948. The open surgical method has now largely been abandoned in favour of the minimally invasive robot-assisted method, which was first described in 2000. Until 1980, the procedure was hazardous, often accompanied by massive blood loss and poor outcomes. For patients in whom surgery is indicated, prostatectomy is increasingly being used as the first step in a multitherapeutic approach in advanced local, and even early metastatic, disease. However, contemporary molecular insights have enabled many men to safely avoid surgical intervention when the disease is phenotypically indolent and use of active surveillance programmes continues to expand worldwide. In 2020, surgery is not recommended in those men with low-grade, low-volume Gleason 6 prostate cancer; previously these men - a large cohort of ~40% of men with newly diagnosed prostate cancer - were offered surgery in large numbers, with little clinical benefit and considerable adverse effects. Radical prostatectomy is appropriate for men with intermediate-risk and high-risk disease (Gleason score 7-9 or Grade Groups 2-5) in whom radical prostatectomy prevents further metastatic seeding of potentially lethal clones of prostate cancer cells. Small series have suggested that it might be appropriate to offer radical prostatectomy to men presenting with small metastatic burden (nodal and or bone) as part of a multimodal therapeutic approach. Furthermore, surgical treatment of prostate cancer has been reported in cohorts of octogenarian men in good health with minimal comorbidities, when 20 years ago such men were rarely treated surgically even when diagnosed with localized high-risk disease. As medical therapies for prostate cancer continue to increase, the use of surgery might seem to be less relevant; however, the changing demographics of prostate cancer means that radical prostatectomy remains an important and useful option in many men, with a changing indication.

Time Trends for Prostate Cancer Incidence from 2003 to 2013 in South Korea: An Age-Period-Cohort Analysis.

PURPOSE: Prostate cancer (PCa) incidence is affected by aging phenomenon and performance of screening test. In United States, PCa incidence is affected by period effect of U.S. Preventive Services Task Force (USPSTF) recommendation. However, no study has reported the effect of USPSTF recommendation or aging phenomenon on PCa incidence in South Korea. Thus, the objective of this study was to investigate effects of age, period, and birth cohort on PCa incidence using age-period-cohort analysis. MATERIALS AND METHODS: Annual report of cancer statistics between 2003 and 2013 from National Health Insurance Service (NHIS) in South Korea for the number of PCa patients and Korean Statistical Information Service (KOSIS) data between 2003 and 2013 from national statistics in South Korea for the number of Korean male population were used. Age-period-cohort models were used to investigate effects of age, period, and birth cohort on PCa incidence. RESULTS: Overall PCa incidence in South Korea was increased 8.8% in annual percentage (95% confidential interval, 6.5 to 11.2; p < 0.001). It showed an increasing pattern from 2003 to 2011 but a decreasing pattern from 2011 to 2013. Age increased the risk of PCa incidence. However, the speed of increase was slower with increasing age. PCa incidence was increased 1.4 times in 2008 compared to that in 2003 or 2013. Regarding cohort effect, the risk of PCa incidence started to increase from 1958 cohort. CONCLUSION: PCa incidence was affected by period of specific year. There was a positive cohort effect on PCa incidence associated with age structural change.

United States trends in active surveillance or watchful waiting across patient socioeconomic status from 2010 to 2015.

BACKGROUND: Prospective evidence supports active surveillance/watchful waiting (AS/WW) as an efficacious management option for low-risk prostate cancer that avoids potential treatment toxicity. AS/WW schedules require regular follow-up and adherence, and it is unknown to what extent patient socioeconomic status (SES) may impact management decisions for AS/WW. We sought to determine whether AS/WW use in the United States differs according to patient SES. DESIGN: Using the Surveillance, Epidemiology, and End Results Prostate with AS/WW Database, all adult men diagnosed with localized low-risk prostate cancer (clinical T1-T2a, Gleason 6, and prostate-specific antigen <10 ng/mL) and managed with either AS/WW, radical prostatectomy, or radiotherapy were identified between 2010 and 2015. SES tertile was measured by the validated Yost Index (low: 0-10,901; middle: 10,904-11,469; high: 11,470-11,827). AS/WW trends were defined across SES tertiles from 2010 to 2015. Logistic multivariable regression defined adjusted odds ratios (aOR) for receipt of AS/WW by SES tertile. RESULTS: In 50,302 men, AS/WW use was higher with increasing SES tertile (24.6, 25.3, and 30.5% for low, middle, and high SES tertiles, respectively; PTrend (SES) <0.001). From 2010 to 2015, AS/WW use in the low, middle, and high SES tertiles increased from 11.2 to 37.3%, 14.1 to 45.8%, and 17.6 to 46.4%, respectively (PTrends <0.001). By 2015, likelihood of AS/WW became comparable among the middle vs. high SES tertiles (aOR 0.96, 95% confidence interval (CI): 0.83-1.11, P = 0.55), but remained lower among the low vs. high SES tertile (aOR 0.73, 95% CI: 0.64-0.83, P < 0.001). CONCLUSIONS: AS/WW use for low-risk prostate cancer in the US differs by SES. Despite increases in AS/WW across SES from 2010 to 2015, patients from low SES received significantly lower rates of AS/WW compared with higher SES groups. SES may therefore influence management decisions, where factors associated with low SES might act as a barrier to AS/WW, and may need to be addressed to reduce any disproportionate risk of unnecessary treatment to lower SES patients.

[Radical prostatectomy through the years]. / Die radikale Prostatektomie im Wandel der Zeit.

The operative aspect of radical prostatectomy has changed dramatically in the past 200 years as significant technological advances have been made, particularly during the past 50 years. The work of Dr. Walsh in the late 1970 s and early 1980 s led to a significant reduction in surgical morbidity and is considered an important milestone of radical prostatectomy, as is the introduction of minimally-invasive (robotic-assisted) surgical techniques. Yet there is no absolute gold standard regarding surgical approaches. Innovative tools, e. g. the addition of "augmented reality", are currently under investigation. This review article for the anniversary issue of "Der Urologe" aims to cover the milestones of the evolution of this "signature" surgery in the field of urology.

The Genomics of Prostate Cancer: A Historic Perspective.

The genomics of prostate cancer (PCA) has been difficult to study compared with some other cancer types for a multitude of reasons, despite significant efforts since the early 1980s. Overcoming some of these obstacles has paved the way for greater insight into the genomics of PCA. The advent of high-throughput technologies coming from the initial use of microsatellite and oligonucleotide probes gave rise to techniques like comparative genomic hybridization (CGH). With the introduction of massively parallel genomic sequencing, referred to as next-generation sequencing (NGS), a deeper understanding of cancer genomics in general has occurred. Along with these technologic advances, there has been the development of computational biology and statistical approaches to address novel large data sets characterized by single base resolution. This review will provide a historic perspective of PCA genomics with an emphasis on the cardinal mutations and alterations observed to be consistently seen in PCA for both hormone-naïve localized PCA and castration-resistant prostate cancer (CRPC). There will be a focus on alterations that have the greatest potential to play a role in disease progression and therapy management.

Family History of Breast or Prostate Cancer and Prostate Cancer Risk.

PURPOSE: Breast and prostate cancer co-occur in families, and women with a family history of prostate cancer are at increased breast cancer risk. Prostate cancer is among the most heritable cancers, but few studies have investigated its association with familial breast cancer. The objective of this study is to investigate the extent to which familial breast or prostate cancer in first-degree relatives increases prostate cancer risk. EXPERIMENTAL DESIGN: A prospective study of 37,002 U.S. men in the Health Professionals Follow-up Study. During the 16-year follow-up to 2012, 4,208 total and 344 lethal cases were diagnosed. Using cause-specific hazards regression, we estimated the multivariable HRs and 95% confidence intervals (CI) for associations between familial breast or prostate cancer and total and lethal prostate cancer. RESULTS: Those with familial breast cancer had a 21% greater risk of prostate cancer overall (95% CI, 1.10-1.34), and a 34% greater risk of lethal disease (HR 1.34; 95% CI, 0.96-1.89). Family history of prostate cancer alone was associated with a 68% increased risk of total disease (95% CI, 1.53-1.83) and a 72% increased risk of lethal disease (95% CI, 1.25-2.38). Men with a family history of both cancers were also at elevated risk. CONCLUSIONS: Our study found that men with a family history of breast or prostate cancer had elevated prostate cancer risks, including risk of lethal disease. These findings have translational relevance for cancer risk prediction in men.

Extensive periosteal new bone formation in a skeleton from post-Medieval Chichester, England: A probable case of metastatic prostatic carcinoma.

An elderly male skeleton from a site in Chichester, UK, was found with a widespread periosteal reaction, principally affecting the axial skeleton and the pelvis. Radiography showed the presence of sclerosing infiltrates, mainly involving the lumbar vertebrae and pelvis. The differential diagnosis is discussed, reaching the conclusion that hypertrophic osteo-arthopathy (HOA) is the only reasonable alternative condition likely to produce such a widespread periosteal reaction as found here. HOA does not produce secondary deposits in the skeleton, however, and we conclude that his is most likely a case of prostatic carcinoma.

Historical and contemporary perspectives on cribriform morphology in prostate cancer.

The Gleason scoring system is widely used for the grading and prognostication of prostate cancer. A Gleason pattern 4 subtype known as cribriform morphology has now been recognized as an aggressive and often lethal pattern of prostate cancer. The vast majority of published and ongoing prostate cancer studies still do not acknowledge the prognostic differences between various Gleason pattern 4 morphologies. As a result, current treatment recommendations are likely to be imprecise and not tailored towards patients who are most likely to die from the disease. Use of active surveillance for patients with Gleason score 3 + 4 prostate cancer has been suggested. However, the success of such paradigms would require cribriform morphology to be reported at the time of prostate biopsy, as patients harbouring such a pattern are poor candidates for surveillance. To date, only a limited number of studies have described the molecular alterations that occur in the cribriform morphological pattern. Further refinement of prostate cancer grading paradigms to distinguish cribriform from noncribriform Gleason pattern 4 is essential.

Possible prostate cancer in northern Peru: Differential diagnosis, vascular anatomy, and molecular signaling in the paleopathology of metastatic bone disease.

This paper describes four possible cases of metastasized prostate cancer in archaeological human skeletons from the north coast of Peru spanning the Middle Sicán to Colonial eras (roughly A.D. 900-1600). Varying combinations of exuberant abnormal new bone formation and some abnormal bone loss affecting lumbar vertebrae and the bony sacrum were observed in these individuals. Detailed lesion descriptions are followed by a differential diagnosis that systematically eliminates pseudopathology, infectious diseases, sclerosing bone disorders, and most metastatic processes. However, metastasized prostate cancer cannot be rejected and is highly consistent with the observed lesions. Metastasized pancreatic, bladder, or carcinoid tumors represent additional, though far less likely, diagnostic options. Anatomical and molecular signaling factors further validate this differential diagnosis. The paravertebral venous plexus of Baston plays an anatomical role in the metastatic seeding of lumbar vertebra from prostate cancer. Further, abundant molecular signaling mechanisms upregulate multiple bone-forming mechanisms in prostate metastases, though initially such lesions may originate as lytic phenomena. These multiple lines of evidence help demonstrate a multi-level framework for explanation in paleopathology and especially to help better elucidate the complexities of ancient neoplastic diseases.

No change in the prevalence of latent prostate cancer over the last 10 years: a forensic autopsy study in Japan.

Although the morbidity rate of prostate cancer has increased with 2.3 times in these 10 years in Japan, little is known about the changes in the prevalence of latent prostate cancer. To understand changes in the prevalence of latent prostate cancer, a retrospective analysis was performed. Forensic autopsy findings from Tochigi Prefecture between September 2012 and February 2014 were collected. Two cross sections, from the base and apex of the prostate, were examined histopathologically. The prevalence of latent prostate cancer was compared with findings from forensic autopsies performed between August 2002 and July 2005 in the same region. The prevalence of latent prostate cancer in both groups was similar, showing an overall prevalence of 13.6% and 12.2% and a Gleason score >6 of 6.2% and 7.1%, respectively. When prevalence was compared by cause of death, the values were similar for both groups. The prevalence of latent prostate cancer in this Japanese population did not show any significant change over the past 10 years. The dramatic increase in morbidity rate for prostate cancer could be from the increase in prostate-specific antigen screening and subsequent referral to urologists.