Urologic cancer in China

Abstract

Cancer remains to be the second most common cause of death, and its incidence and mortality rates are increasing in China. According to the 2015 National Central Cancer Registry (NCCR) of China, the incidence of bladder cancer and prostate cancer ranked sixth and seventh, respectively, in male cancers. The majority of prostate cancer patients were diagnosed at an advanced stage. Early diagnosis of prostate cancer is the key to improve prostate cancer survival in China. Radical prostatectomy or radical radiotherapy is the main treatment for localized prostate cancer, and a comprehensive therapy based on androgen deprivation therapy is the treatment for advanced disease. The most common histologic types of bladder cancer in China were urothelial carcinoma, followed by adenocarcinoma and squamous carcinoma. The majority of patients were diagnosed using white-light cystoscopy with biopsy. Fluorescence and narrow-band imaging cystoscopy had additional detection rates and are becoming more popular. Following Chinese guidelines, most non-muscle invasive bladder cancer patients were treated with diagnostic transurethral resection and more than half of the muscle invasive bladder cancer patients were treated with radical cystectomy. Due to the increased detection rate of kidney tumors by ultrasound in physical examination, the number of incidentally diagnosed renal cell carcinoma has increased. Localized kidney cancers are more and more often treated by nephron-sparing surgery. Radical nephrectomy is still the main treatment option for patients with locally advanced renal cell carcinoma. Both laparoscopic and robotic-assisted laparoscopic surgeries have been used in big medical centers. Both testicular cancer and penile cancer have lower incidence levels than that in Europe. As we have an enormous population base, the absolute patient number is big. The diagnosis and treatment follows the Chinese guidelines. In China, both medical professionals and public should concern more on the early diagnosis, as there is not enough cancer prevention information available. Urologists should also take a more active role in educating the population.

prostrate cancer, bladder cancer, kidney cancer, diagnosis, treatment

Introduction

As in other countries, cancer is a major public health issue in China. It is the second leading cause of death. Cancer incidence and mortality rates are increasing in Chinese population.

Recently, the National Central Cancer Registry (NCCR) of China has released its 2015 annual report based on registry data (1). In this cancer statistics report of incidence and mortality in cancer registration areas in 2011, it has shown that the crude incidence rate of all cancers was 250.28/10⁵ (277.77/10⁵ in male and 221.37/10⁵ in female) and the crude mortality rate of all cancers was 156.83/10⁵ (194.88/10⁵ in male and 116.81/10⁵ in female), with 6.4 and 5.4% increases of the incidence rate and mortality compared with the figures in 2010. In the top 10 cancer incidences in both sex, lung cancer was the most common cancer, prostate cancer ranked ninth with an incidence of 7.10/10⁵. This was the first time that urologic cancer entered the top 10 cancers in Chinese population.

According to Globocan 2012, the 20 most common cancers in both sexes in China include prostate cancer (eighth), bladder cancer (12th) and kidney cancer (17th) (2).

The rising trends could be caused by the high prevalence of tobacco consumption and the air pollution due to the rapid development of urbanization and industrialization. Other common causes of cancer, like unhealthy diet, chronic infection, longer life expectancy, unbalanced development, limited national health insurance coverage, low level of awareness, low level of medical care in rural area, all may contribute to the increasing incidence and mortality rates in China.

Chinese government has made a lot of efforts to improve cancer screening, diagnosis and treatment. The population-based NCCR of China collects the information on cancer statistics of both incidence and mortality rates from covered population to monitor the cancer epidemic. The cancer registration data of NCCR are not only applied for cancer control planning, implementation and evaluation on cancer prevention and control, but also for cancer-related research. In basic research, the National Natural Science Foundation of China had supported over 2573 projects and funded over 3 billion US dollars in life science including cancer research in 2013 (3). The research results had not only benefited Chinese people, but also contributed to the development of cancer research in the world. Cancer Hospital Chinese Academy of Medical Sciences in Beijing, Fudan University Shanghai Cancer Center in Shanghai, Sun Yat-sen University Cancer Center in Guangzhou and other local cancer hospitals in every province are the comprehensive cancer centers in China. These integrated cancer hospitals not only focus on the early diagnosis and treatment of cancers with surgery, radiotherapy, chemotherapy, interventional therapy, immunotherapy, gene therapy and Traditional Chinese Medicine (TCM) with multidisciplinary treatment that strictly follow national and international standards, but also on conducting cancer clinical research, teaching, education and prevention. The State Key Laboratory (SKL) of Oncology covering a broad spectrum in oncology from basic to translational and clinical research by the Ministry of Science and Technology in China was established in Sun Yat-Sen University Cancer Center. Tumor tissue bank with a dynamic collection of biological samples, like prostate cancer tissue bank in Fudan University Shanghai Cancer Center, has been established in major cancer hospitals for cancer research.

In this review, we would highlight the status of prostate cancer, bladder cancer, kidney cancer, testicular cancer and penile cancer in China.

Prostate cancer

According to NCCR of China 2015 annual report, the overall incidence of prostate cancer was 7.1/10⁵ populations in 2011. This figure ranked ninth in the highest cancer incidences for all sexes and seventh in male. There were differences in prostate cancer incidence and mortality rates in urban and rural areas. Prostate cancer incidences were 10.06/10⁵ in urban area, and with a lower rate of 4.79/10⁵ in rural area. Prostate cancer mortality rates were 2.98/10⁵ for the whole population, 3.95/10⁵ in urban area and 1.97/10⁵ in rural area, respectively (1).

Chinese urologists have put enormous efforts in improving screening and treatment of prostate cancer with advanced techniques like da Vinci system and new concept of cytoreductive radical prostatectomy for metastatic prostate cancer patients. Organized by Chinese Urological Association (CUA), the Chinese version CUA prostate cancer diagnosis and treatment guideline was first published in 2007 and was renewed every 2 years. The newest is 2014 version. This guideline cites many Chinese data, but it is in line with international guidelines, such as European Association of Urology (EAU) guidelines. This guideline covers contents of epidemiology, diagnosis, treatment, follow up, management of recurrence, castration-resistant prostate cancer (CRPC) and diagnosis and treatment for bone metastatic patients. As this guideline is in Chinese, both Chinese urological specialists and general practitioners at any levels can use it, which has helped them in providing better service and updated clinical practice (4). To help patients and their relatives understanding prostate cancer better, there are various versions of patient information available online. Recently, EAU and CUA have reached an agreement of translating EAU patient information into Chinese, added one more resource.

So far, there was no consensus in China on prostate screening because of the concern about over diagnosis and treatment and no enough supportive evidence, in particular, the lack of Chinese-based data. But the CUA guideline does suggest regular PSA and DRE for males over 50 years and for males over 45 years with a family prostate cancer history. Indications for prostate biopsy are similar to EAU guidelines (5). The standard prostate biopsy is transrectal ultrasound-guided prostate biopsy. However, there are more and more institutes using ultrasound-guided transperineal prostate biopsy because of relatively lower complication rate and more biopsy cores obtained. The indication of radical prostatectomy has been expanded from localized prostate cancer to positive pelvis lymph node and T3b prostate cancers using the technique from laparoendoscopic single-site radical prostatectomy (RP) to da Vinci robotic-assisted laparoscopic RP (RALRP) (6,7). Cytoreductive radical prostatectomy has been discussed and conducted in high-volume centers and experienced hands through open and RALRP. Both retrospective and prospective related clinical trials are ongoing (8–12). In this aspect, Chinese urologists are in the cutting edge with their colleagues in developed countries. Radiotherapy is routinely offered to prostate cancer patients. Techniques such as external beam radiotherapy, brachytherapy and even proton and heavy ion are available in different regions depending on the economic development levels. Follow-up and salvage therapy after radical prostatectomy and radiotherapy has been standardized in the CUA prostate cancer guidelines. For CRPC treatment, docetaxel-based chemotherapy has been well accepted by urologists and oncologists. Cabacitaxel is not available in China yet. Abiraterone acetate has been approved for the indication of both pre- and post-chemotherapy by China Food and Drug Administration (CFDA) and is available in the Chinese market. Enzalutamide is still in the clinical trial according to CFDA regulations.

The Chinese Prostate Cancer Consortium (CPCC) has conducted both basic scientific research and clinical studies. A recent CPCC collaboration study showed that Chinese patients accepting prostate biopsy have higher PSA level, smaller prostate volume and higher Gleason scores comparing with the data of American. They have also found that G135E mutation is associated with the increased PCa risk in Chinese men (13).

Ye Dingwei from Shanghai and Zhu Gang from Beijing as panel members have contributed to the work of NCCN clinical practice guidelines in Oncology Asia Consensus Statement: Prostate Cancer.

Chinese Prostate Cancer Database (C-CaP) has been initiated in September 2013. The aims of C-CaP are to collect and analyze Chinese prostate cancer patient data in diagnosis, treatment and follow-up, to provide good evidences for better diagnosis and treatment of prostate cancer. The Asia prostate study group (A-CaP) has launched in December 2015 and will work on the collaboration project with other Asia countries for prostate cancer study, and C-CaP is active in this study group as the launch country (14).

Bladder cancer

In China, bladder cancer is one of the most common urologic malignancies (1). In the past few years, the incidence and mortality rates have increased gradually. According to the NCCR of China 2015 annual report, the overall incidence of bladder cancer was 7.68/10⁵ in 2011. This figure ranked sixth in male cancers. There were differences in bladder cancer incidence and mortality rates in urban and rural area. Bladder cancer incidences were 9.36/10⁵ in urban area, and 5.49/10⁵ in rural area. Bladder cancer mortality rates were 1.99/10⁵ in population, 3.43/10⁵ in urban area, 2.62/10⁵ in rural area, 3.03/10⁵ in male and 0.88/10⁵ in female. However, the incidence of bladder cancer was lower than the western countries.

Smoking and occupational exposures are still the major risk factors, whereas chronic infection with Schistosoma hematobium is relatively rare (4).

As with prostate cancer, we have CUA bladder cancer guidelines in line with EAU guideline, but more practical for the Chinese urologist (4).

In fact, diagnosis and treatment for bladder cancer in China may be different from Western countries. To gain the unique bladder cancer data in China, Chinese Bladder Cancer Consortium (CBCC) conducted a cross-sectional investigation in 44 member centers and generated a database of bladder cancer. From January 2007 to December 2012, clinical data of 14 260 BCA cases were retrospectively collected and analyzed.

According to this study, the most common histologic types of bladder cancer were urothelial carcinoma (91.4%), adenocarcinoma (1.8%) and squamous carcinoma (1.9%). Of note, 42.0, 41.0 and 17.0% of patients were of pathological Grade 1, 2 and 3. Of note, 16.0, 48.7 and 35.3% of patients were papillary urothelial neoplasms of low malignant potential, low grade and high grade, respectively. Non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC) were 74.1 and 25.2%, respectively (0.8% not clear). Carcinoma in situ was only 2.4%. Most patients were diagnosed using white-light cystoscopy with biopsy (74.3%). Fluorescence and narrow-band imaging cystoscopy had additional detection rates of 1.0 and 4.0%, respectively. Diagnostic transurethral resection (TUR) provided a detection rate of 16.9%. Most NMIBCs were treated with TUR (89.2%). After initial TUR, 2.6% accepted second TUR, and 45.7, 69.9 and 58.7% accepted immediate, induced and maintenance chemotherapy instillation, respectively. Most MIBCs were treated with radical cystectomy (RC, 59.7%). Laparoscopic RCs were 35.1%, whereas open RCs were 63.4%. Extended and standard pelvic lymph node dissections were 7 and 66%, respectively. Three most common urinary diversions were orthotopic neobladder (44%), ileal conduit (31%) and ureterocutaneostomy (23%). Only 2.3% of patients accepted neo-adjuvant chemotherapy and only 18% of T3 and T4 patients accepted adjuvant chemotherapy (15). The CBCC concluded that the disease characteristics are similar to international reports, while differences of diagnosis and treatment exist. CBCC study has provided new evidences for the future revision of the CUA bladder cancer guideline.

Ye Dingwei from Shanghai and Zhu Gang from Beijing as panel members have contributed to the work of NCCN clinical practice guidelines in Oncology Asia Consensus Statement: Bladder Cancer.

Kidney cancer

According to the NCCR of China 2015 annual report, the overall incidence of kidney cancer was 3.35/10⁵ in 2011. Kidney cancer incidences were 3.35/10⁵ in population, 4.73/10⁵ in urban area, 1.89/10⁵ in rural area, 4.38/10⁵ in male and 2.23/10⁵ in female. Kidney cancer mortality rates were 1.12/10⁵ in population, 1.44/10⁵ in urban area, 0.79/10⁵ in rural area, 1.43/10⁵ in male and 0.81/10⁵ in female. However, this variation epidemiologic data may be because of unbalanced development in China (1).

In China, the diagnosis and treatment of renal cell carcinoma (RCC) patients are varied, even there is a CUA RCC guideline. Li et al. (16) conducted a study in 2010 to analyze the clinical characteristics of RCC and unveil the status of diagnosis and treatment from 23 medical centers cover different areas of China in 2010. They had reviewed 1975 new cases, with 1329 males and 634 females. The male and female ratio was about 2.1:1.0. Of all cases, 1238 patients (62.7%) were asymptomatic and were detected by physical examination, whereas 711 patients (36.0%) were symptomatic. Of note, 1844 patients had been surgically treated, 1500 (81.3%) underwent radical nephrectomy and 325 (17.6%) underwent partial nephrectomy. Among the operations, open surgery was performed in 1493 cases (81.0%) and laparoscopic procedure was performed in 351 cases (19.0%). They have concluded that routine health check-up was the important way to find early stage RCC. Open radical nephrectomy was the most often used surgical treatment option in the Chinese centers at the time of study.

Li et al. (17) conducted another RCC study in 18 Chinese hospitals from 2008 to 2012 to assess the change of concept in RCC management. There were 6853 RCC, including 4529 males and 2324 females, with an average age of 56.0 years. Clear cell RCC was the predominant pathology type, with a total of 3517 cases (51.32%). Among the 6853 patients, 2495 accepted laparoscopic surgery (36.41%), 3891 accepted open surgery (56.78%) and 467 accepted other treatment options (6.81%). Of note, 1935 patients (30.30%) received nephron-sparing surgery, whereas 4451 patients (69.70%) received radical nephrectomy. They concluded that, in China, the predominant pathological subtype of RCC was clear cell RCC, and surgery was the main treatment option, whereas the proportion of laparoscopic surgery and nephron-sparing surgery was increasing gradually.

Tang et al. (18) have evaluated the prognostic outcomes and risk factors for RCC patients with venous tumor thrombus in China. In their series, the median survival time was 63 months. The 5-year overall survival and cancer-specific survival rates were 53.6 and 54.4% for all patients. The significant survival difference was only observed between early (below hepatic vein) and advanced (above hepatic vein) tumor thrombus. There were reports of robotic-assisted or pure laparoscopic radical nephrectomy and tumor thrombectomy achieved by Chinese urologists, Zhang Xu and Ma Lulin. Further evaluation of the safety, clinical efficiency and feasibility of this treatment option is under study.

In the past, immunotherapy using IFN-α and interleukin-2 were the main treatment options for the advanced RCC in China. These types of treatment have almost been abandoned due to their toxicities and low response rates. Currently, targeted therapy using tyrosine kinase inhibitors such as sunitinib malate, sorafenib tosylate and everolimus is the standard therapy for advanced diseases. However, as in other developing countries, socio-economic factors should be considered carefully.

In August 2014, the Chinese Kidney Cancer Consortium (CKCC) was established and focused on integration of data of RCC from different hospitals in China. CKCC will also promote the development of screening, prevention and treatment of RCC in China, which could guide Chinese urologists to manage their kidney cancer cases better.

Ye Dingwei from Shanghai and Zhu Gang from Beijing as panel members have contributed to the work of NCCN clinical practice guidelines in Oncology Asia Consensus Statement: kidney Cancer.

Testicular cancer

According to the NCCR of China 2015 annual report, the overall incidence of testicular cancer was 0.46/10⁵ male in 2011. Testicular cancer incidences were 0.53/10⁵ male in urban area and 0.39/10⁵ male in rural area. Compared with the 3–10/10⁵ male in Western society (19), it was lower. Testicular cancer mortality was 0.11/10⁵ in population, 0.12/10⁵ in urban area and 0.09/10⁵ in rural area. When compared with the testicular cancer mortality in EU of 0.35/10⁵ in the year 2000–04, it was lower as well (20).

The diagnosis and treatment of testicular cancer follows the CUA guidelines (4). Organ preserving surgery is indicated in bilateral testicular cancer or tumor in solitary testis with a tumor volume less than 30% of the testis and should be followed by adjuvant radiotherapy.

Penile cancer

According to the NCCR of China 2015's annual report, the overall incidence of penile cancer was 0.6/10⁵ in male in 2011. Penile cancer incidences were 0.61/10⁵ in urban area and 0.6/10⁵ in rural area. Penile cancer mortality was 0.18/10⁵ in male and in population, 0.19/10⁵ in urban area and 0.17/10⁵ in rural area. When compared with the penile cancer mortality in EU of 0.35/10⁵ in the year of 2000–04 (20), it was lower.

In the CUA penile cancer guideline, penile cancer was linked to phimosis, redundant prepuce, HPV infection, etc. Radical inguinal lymphadenectomy was regarded as a lifesaving treatment that was suggested to be performed on N1–N2 patients (4).

Conclusion

Urologic cancer incidence and mortality rates are increasing in China during this decade. There is still a high percentage of prostate cancer patients diagnosed at advanced stages. There is a need to use fluorescence and narrow-band imaging cystoscopy techniques in improving bladder cancer diagnosis detection rate. There is a trend of more laparoscopic radical nephrectomy and partial nephrectomy used in the treatment of kidney cancers. Even the incidence rates were low; the absolute number of testicular cancer and penile cancer patients was high. Application of CUA guidelines has improved Chinese urologic cancer diagnosis and treatment. Early diagnosis of the urologic cancer is the key to improve urologic cancer survival in China.

Conflict of interest statement

None declared.