I. Incidence and mortality of prostate cancer worldwide and current major problems in China In 2008, there were about 899,000 new cases of prostate cancer and 258,000 prostate cancer deaths worldwide, ranking second in incidence and sixth in mortality of malignant tumors in men, respectively. With the increase in the total world population and the aging trend, the annual number of new cases of prostate cancer is expected to reach 1.7 million and 499,000 deaths due to prostate cancer by 2030. The incidence of prostate cancer varies widely by region, with North America and Scandinavia having the highest incidence of prostate cancer and most of Asia, including China, having a low incidence. Although there are large regional differences in the incidence of prostate cancer, the incidence of prostate cancer has increased significantly in most countries over the past 30 years. The incidence of prostate cancer in some developed regions of China has also increased rapidly. The incidence rate in Shanghai increased 3.5 times from 1997 to 1999 compared to 1985-1987, and in 2000 the incidence rate reached 7.7 per 100,000, surpassing bladder tumors and ranking first among male genitourinary tumors. Although the difference in prostate cancer incidence between the United States and China was significant (78-fold, 2002 data), the difference in prostate cancer mortality was much smaller (16-fold, 2002 data). The ratio of tumor mortality to incidence is an indicator of tumor lethality. Although the United States has one of the highest incidence and mortality rates for prostate cancer in the world, the ratio of mortality to incidence is lower than in Asian countries such as China and is still decreasing. Why is there such a difference? This is because in the United States, due to the widespread testing of Prostate Specific Antigen (PSA) and the high public awareness of prostate cancer, 75% of prostate cancer patients are diagnosed with elevated PSA alone, and 91% of patients have clinically limited prostate cancer, which is suitable for treatment by surgery or radiation therapy that may cure prostate cancer. Since the 1990s, the 5-year survival rate of prostate cancer patients in the United States has reached over 90%. The median PSA is 46.1ng/ml. Since most patients have advanced disease, the treatment is not effective and the long-term prognosis is poor. The early detection of prostate cancer is important to improve the outcome of prostate cancer treatment and reduce the death of patients due to prostate cancer. Screening and early detection of prostate cancer Tumor screening is an effective means of early detection of tumors. Two articles published in the same issue of the New England Journal of Medicine in 2009 reported the results of two large studies on the impact of prostate cancer screening on patient mortality. The PLCO Oncology Screening Trial (Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial), conducted in the United States, involved 76,693 men at 10 centers. Participants were divided into two groups: one group received annual PSA testing and anal examinations, and the other group underwent only routine health care measures. After 7 years of follow-up, the results showed a low mortality rate due to prostate cancer (2.0 per 10,000 in the screening group and 1.7 per 10,000 in the control group), with no significant difference in prostate cancer-specific mortality between the screening and control groups. In the same issue of the journal, the results of the European Randomized Study of Screening for Prostate Cancer (ERSPC) study conducted in Europe were also reported. The purpose of the study was also to examine the impact of PSA-based prostate cancer screening on patient mortality. The study included 162,243 men aged 55 to 69 years from seven European countries. The participants were randomized into two groups, one receiving PSA testing on average once every four years and the other not. After 9 years of follow-up, the results of the study showed that PSA test-based prostate cancer screening reduced prostate cancer-specific mortality by 20%; by 11 years of follow-up, the reduction in prostate cancer-specific mortality was further evident in the screening group, at 21%. Why did two similar studies yield inconsistent results? Through an in-depth analysis of the data from both studies, the researchers found that 40% of the study participants in the PLCO study, who were not supposed to have PSA testing, had PSA testing during the first year of the study, and the percentage of those in the control group who had PSA testing rose to 52% by the sixth year of the study. Second, only about half of the study participants in the PLCO study who had an indication for a prostate puncture biopsy actually underwent one. In addition, differences in the number of participants, follow-up time, specific screening measures, and puncture biopsy criteria between the two studies also had an impact on the results of the studies. Because the specific implementation of the ERSPC study protocol was more rigorous, most scholars now believe that the results of the ERSPC study are more credible than those of the PLCO in that PSA test-based prostate cancer screening reduces patient deaths due to prostate cancer. At the same time, as the ERSPC investigators point out, although PSA test-based prostate cancer screening can reduce prostate cancer-specific mortality, the cost of this reduction is significant: for every 1 reduction in prostate cancer deaths, approximately 1,410 people need to be screened for prostate cancer and 48 people need to be treated for prostate cancer. Because of the enormous cost and the significant differences in the biological behavior of prostate cancer from patient to patient, and the problem of overtreatment of clinically occult prostate cancer detected by screening, there is still a large controversy among scholars as to whether PSA test-based prostate cancer screening should be promoted in the population, and there is no clear consensus. However, it should be emphasized that early detection of prostate cancer, especially in the current situation where most clinically detected prostate cancers in China are advanced and lost to radical treatment, is still one of the priorities that medical practitioners, especially those practicing urological specialties, should strive to improve. The combination of rectal examination and PSA testing is currently recognized as the best primary screening method for early detection of prostate cancer. As a single test, PSA has a higher predictive rate of positive prostate cancer diagnosis compared to rectal examinations, and can improve the diagnosis of clinically limited prostate cancer and increase the chance of radical prostate cancer treatment. For the timing of PSA testing, the Chinese Medical Association Urology Section has made specific recommendations for early diagnosis of prostate cancer: routine PSA testing and rectal examinations should be performed for men over 50 years of age with lower urinary tract symptoms, and for men with a family history of prostate cancer, regular checkups and follow-ups should begin at age 45. Third, the key to reducing the mortality rate of prostate cancer is to improve the treatment of high-risk prostate cancer Reducing the death of patients caused by prostate cancer is undoubtedly one of the main objectives of prostate cancer treatment. But do all prostate cancers require aggressive treatment? The answer is no. The specific biological behavior of prostate cancer is complex from patient to patient, and some prostate cancers develop slowly and remain unaffected by prostate cancer throughout the patient’s life, “living in peace” with prostate cancer. Some prostate cancers are highly malignant (high-risk prostate cancer) and develop rapidly, quickly leading to urinary tract obstruction and bone metastases, which can seriously affect patients’ lives and quality of life. The key to reducing the mortality rate of prostate cancer is to detect and distinguish high-risk prostate cancer, treat it aggressively and follow it up closely. But how can we distinguish high-risk prostate cancer? Or what specific criteria should we use to determine whether a patient has a high-risk type of prostate cancer? Up to now, there is no international standard for the definition of high-risk prostate cancer, but different scholars and academic organizations have proposed broadly similar and slightly different criteria for determining high-risk prostate cancer based on PSA level, Gleason score, clinical staging, etc. What is the best way to treat high-risk prostate cancer after detection? There are three main types of treatment for prostate cancer: radical surgery, radiotherapy and endocrine therapy. After long-term research and clinical follow-up, scholars have found that for high-risk prostate cancer, none of the treatments alone can achieve satisfactory treatment results. For high-risk prostate cancer, radiotherapy combined with endocrine therapy is usually used. Several studies have found that radiotherapy combined with endocrine therapy has improved tumor-specific survival and overall survival of patients compared to the application of radiotherapy or endocrine therapy alone Previously, for high-risk prostate cancer, most scholars believe that radical prostatectomy is not effective in the treatment of prostate cancer. Because of the high likelihood of positive margins, pelvic lymph node metastases, and recurrent metastases after surgery, and the difficulty of surgery, radical prostatectomy is only one of the “optional” treatment options and is not widely used in the treatment of high-risk prostate cancer patients. In recent years, a growing number of studies have found that a combination of radical surgery and pelvic lymph node dissection is no less effective than radiation therapy. There are no randomized controlled prospective clinical studies comparing the difference in outcomes between radiotherapy and radical surgery for high-risk prostate cancer. However, well-designed prospective case studies have found that for high-risk prostate cancer, patients treated initially with radical surgery had lower distant tumor metastases and mortality compared to those treated initially with radiotherapy, although the differences were not large in absolute terms. Most scholars now believe that radical prostatectomy is an effective treatment for high-risk prostate cancer. Complications of this procedure are not significantly more common in surgically experienced treatment centers. When radical surgery is performed, an expanded pelvic lymph node dissection is required at the same time, with close postoperative follow-up. An important question for patients with high-risk prostate cancer undergoing radical prostatectomy is whether to proceed to completion of radical surgery if there are metastases in the pelvic lymph nodes. Although there is no high-level medical evidence to answer this question, the conventional wisdom is that radical surgery in the presence of pelvic lymph node metastases is not beneficial for long-term survival and therefore radical surgery is not recommended. Engel et al. retrospectively analyzed the data of a group of patients with metastatic tumors in pelvic lymph nodes and found that the overall survival rates at 5 and 10 years were 84% and 64% for patients who continued with radical surgery, while the overall survival rates at 5 and 10 years for those who abandoned surgery because of metastatic pelvic lymph nodes were reduced to 60%. The 5-year and 10-year overall survival rates for those who abandoned surgery because of the presence of metastases in the pelvic lymph nodes were reduced to 60% and 28% [13]. In China, the incidence of prostate cancer remains relatively low worldwide, but the absolute value of the incidence is rapidly increasing. Early detection of prostate cancer using PSA-based assays is a measure that needs to be further enhanced in clinical work. After the detection of prostate cancer, further differentiation of high-risk prostate cancer and the integrated application of radical surgery, radiotherapy and endocrine therapy for different high-risk prostate cancer patients are necessary to obtain good treatment results. Radical surgery, as one of the effective treatment tools, should be more widely applied to high-risk prostate cancer patients to improve the long-term survival rate, improve the quality of life of patients, and further improve the treatment effect of high-risk prostate cancer.