A review of surgical techniques for radical prostatectomy

Since the early 20th century, radical prostatectomy has been used in the treatment of prostate cancer. However, before the widespread acceptance of prostate-specific antigen screening, the majority of cancers were clinically advanced and not amenable to cure, so relatively few men were candidates for this procedure. Modern advances have contributed dramatically to the reduction of complications and morbidity associated with radical prostatectomy. As a result, the procedure has become the most common treatment selected by men with localized prostate cancer. This article reviews several issues regarding radical prostatectomy, including surgical techniques, cancer control, intraoperative localization of the cavernous nerves, patient selection, and laparoscopic versus robotic approaches.     

Laparoscopic prostatectomy: where do we stand?

Laparoscopic radical prostatectomy is an effective treatment for localized prostate cancer. This cost-intensive and technically demanding operation currently takes longer than the standard open procedures, but with increasing experience, it is eventually associated with lower costs and is nearly as fast. As more urologists gain such experience, the laparoscopic approach may challenge the standard approaches.     

Screening for carcinoma of the prostate by digital rectal examination in a randomly selected population.

OBJECTIVE--To study the acceptability, costs, psychosocial consequences, and organisation of screening for carcinoma of the prostate. DESIGN--A randomly selected population was personally invited for digital rectal examination by a urologist and a general practitioner. Further examinations were performed if induration was felt. Each man completed a questionnaire on his response to the examination. SETTING--General practices in the area of Norrköping. PATIENTS--1494 Men aged 50-69 randomly selected from a population of 9026. MAIN OUTCOME MEASURE--Prostates having a firm nodular consistency. RESULTS--Carcinoma of the prostate was suspected in 45 of 1163 patients examined; in 10 by the general practitioners, in 10 by the urologists, and in 25 by both. Forty four men had a fine needle aspiration biopsy, and carcinomas were found in 13 cases. Of these, one had been suspected by the general practitioner, four by urologists, and eight by both. The cost for each man was 11.60 pounds, and the cost for each case of carcinoma detected and treated by potentially curative methods was 2477 pounds. Of the 13 men with carcinoma, 10 underwent radical prostatectomy and one radiotherapy. One man had advanced disease and was given endocrine treatment, another was not treated. Only 193 men felt distress during the initial examination. Of the 44 men who had an aspiration biopsy, 25 experienced anxiety. CONCLUSIONS--Screening for carcinoma of the prostate by a urologist or a general practitioner using digital rectal examination is a cost effective method of early diagnosis. Whether such screening leads to prolonged survival, however, remains doubtful.     

Prostate-specific antigen testing in Ontario: reasons for testing patients without diagnosed prostate cancer

BACKGROUND: The use of the prostate-specific antigen (PSA) test has been increasing rapidly in Canada since its introduction in 1988. The reasons for using the PSA test in patients without known prostate cancer are unclear. This paper reports on the first study in Canada to use physician records to assess the use of PSA testing. METHODS: A questionnaire was mailed to physicians attending 475 patients without diagnosed prostate cancer. The patients were randomly selected from 2 laboratory databases of PSA test records in the greater Toronto area during 1995. The physicians were asked to consult their patient records to avoid recall bias. Information obtained included physician''s specialty, patient''s age at time of PSA test and reason(s) for the test. RESULTS: There were 264 responses (56%), of which 240 (91%) were usable. Of these 240, 63% (95% confidence interval [Cl] 58%-70%) indicated that the test was conducted to screen for prostate cancer, 40% (95% Cl 34%-47%) said it was to investigate urinary symptoms, and 33% (95% Cl 27%-40%) responded that it was a follow-up to a medical procedure or drug therapy. More than one reason was permitted. Of 151 responses indicating screening as one reason for testing, 64% (95% Cl 56%-72%) stated that it was initiated by the patient, and 73% (95% Cl 65%-80%) stated that it was part of a routine examination. For 19%, both investigation of symptoms and screening asymptomatic patients were given as reasons for testing, and for another 19% both follow-up of a medical procedure and screening were given as reasons. Screening was recorded as a reason for testing far more commonly for patients seen by family physicians and general practitioners than for patients seen by urologists (67% v. 29%, p < 0.001). In contrast, the use of PSA testing to diagnose urinary symptoms was more common for patients seen by urologists than for those seen by family physicians and general practitioners (52% v. 37%, p = 0.044). No significant difference was found between physician groups in the use of PSA testing as a follow-up of a medical procedure (42% for urologists and 31% for family physicians and general practitioners). About 24% of the PSA test records were for patients younger than 50 and older than 70 years. PSA testing initiated by patients was more common in the practices of family physicians and general practitioners than in the practices of urologists (44% v. 13%, p < 0.001). INTERPRETATION: Screening for prostate cancer was the most common reason for PSA testing in our study group; it occurred most commonly in the family and general practice setting and was usually initiated by the patient. Differences in reasons for testing were identified by practice specialty. Although PSA screening for prostate cancer is sometimes recommended for men between 50 and 70 years of age, it is being conducted in men outside this age group.     

Management of clinically localized prostate cancer

Critics of screening have stated that early detection of prostate cancer does not necessarily reflect a diminishing death rate from the disease. However, several recent reports have demonstrated that the death rate from prostate cancer is decreasing, representing the most compelling validation for aggressive screening. Prostate cancer can be halted only if there is no evidence of systemic or regional metastases and the disease is confined to the surgical field or the radiation template. Surgeons and radiation oncologists must make a concerted effort to exclude men with regional and systemic metastases who are unlikely to benefit from treatment. With the widespread acceptance of prostate-specific antigen screening, a greater proportion of men are being diagnosed with clinically localized prostate cancer. Both radical prostatectomy and radiation therapy are able to halt disease spread in this significant subset of men, but survival outcomes indicate that radical prostatectomy is a more reliable treatment than radiation therapy for clinically localized prostate cancer. Overall, the immediate treatment-related morbidity of radical prostatectomy and radiation therapy in the modern era is quite low. Radical prostatectomy and radiation therapy appear to have a similar impact on continence and erectile function. There is a need for neoadjuvant and adjuvant therapies that can be utilized in those cases where radical prostatectomy and radiation are less likely to completely eradicate or destroy the cancer.     

The role of the urologist in treating patients with hormone-refractory prostate cancer

Objectives: To ascertain what percentage of urologists' oncology practice is dedicated to the care of prostate cancer patients and to determine urologists' attitudes towards the treatment of patients with metastatic and hormone-refractory prostate cancer (HRPC). An additional objective is to determine urologists' interest in administering various types of chemotherapy in HRPC patients.Materials and Methods: The American Urological Association (AUA) directory of practicing urologists was obtained, and 3000 randomly selected members of the AUA, as well as the complete list of 168 Society of Urologic Oncology (SUO) members, were chosen for the mailing of a 16-item questionnaire. The urologists were asked about how many of their patients have prostate cancer, how many have metastatic disease, and how many have HRPC and are currently receiving intravenous (IV) chemotherapy. In addition, the urologists were queried regarding their level of interest in learning about chemotherapy options as well as learning how to administer chemotherapy.Results: A total of 654 survey questionnaires were completed and returned for tabulation, resulting in a 21% effective response rate. Sixty-four percent of the responding urologists' cancer patients had prostate cancer, 21% had metastatic disease, and 19% had HRPC; only 4% of the urologists currently administer IV chemotherapy themselves. When asked to describe their interest in learning how to deliver and be reimbursed for IV chemotherapy, 26% expressed an extremely low level of interest, 23% a low level of interest, 31% a high level of interest, and 17% an extremely high level of interest. The results of other questions are presented and correlated with the number of years the urologists have been in practice and other demographic data.Conclusions: The management of prostate cancer comprises a major portion of urologists' practices. Almost one half (48%) of the urologists in this survey were interested in administering and being reimbursed for IV chemotherapy. Several chemotherapy regimens have been shown to improve quality of life in patients with HRPC, yet only about 30% of these patients were referred for chemotherapy. If more urologists were able to deliver these drugs, then the number of patients referred for chemotherapy would likely increase, as would accrual to important clinical trials in HRPC. The results of this survey suggest that methods to implement the training and reimbursement of urologists in the use of chemotherapy regimens should be investigated.     

Serum methionine metabolites are risk factors for metastatic prostate cancer progression

Background

Clinical decision for primary treatment for prostate cancer is dictated by variables with insufficient specificity. Early detection of prostate cancer likely to develop rapid recurrence could support neo-adjuvant therapeutics and adjuvant options prior to frank biochemical recurrence. This study compared markers in serum and urine of patients with rapidly recurrent prostate cancer to recurrence-free patients after radical prostatectomy. Based on previous identification of urinary sarcosine as a metastatic marker, we tested whether methionine metabolites in urine and serum could serve as pre-surgical markers for aggressive disease.

Methodology/Principal Findings

Urine and serum samples (n = 54 and 58, respectively), collected at the time of prostatectomy were divided into subjects who developed biochemical recurrence within 2 years and those who remained recurrence-free after 5 years. Multiple methionine metabolites were measured in urine and serum by GC-MS. The role of serum metabolites and clinical variables (biopsy Gleason grade, clinical stage, serum prostate specific antigen [PSA]) on biochemical recurrence prediction were evaluated. Urinary sarcosine and cysteine levels were significantly higher (p = 0.03 and p = 0.007 respectively) in the recurrent group. However, in serum, concentrations of homocysteine (p = 0.003), cystathionine (p = 0.007) and cysteine (p<0.001) were more abundant in the recurrent population. The inclusion of serum cysteine to a model with PSA and biopsy Gleason grade improved prediction over the clinical variables alone (p<0.001).

Conclusions

Higher serum homocysteine, cystathionine, and cysteine concentrations independently predicted risk of early biochemical recurrence and aggressiveness of disease in a nested case control study. The methionine metabolites further supplemented known clinical variables to provide superior sensitivity and specificity in multivariable prediction models for rapid biochemical recurrence following prostatectomy.     

Curated MicroRNAs in Urine and Blood Fail to Validate as Predictive Biomarkers for High-Risk Prostate Cancer

Purpose

The purpose of this study was to determine if microRNA profiling of urine and plasma at radical prostatectomy can distinguish potentially lethal from indolent prostate cancer.

Materials and Methods

A panel of microRNAs was profiled in the plasma of 70 patients and the urine of 33 patients collected prior to radical prostatectomy. Expression of microRNAs was correlated to the clinical endpoints at a follow-up time of 3.9 years to identify microRNAs that may predict clinical response after radical prostatectomy. A machine learning approach was applied to test the predictive ability of all microRNAs profiled in urine, plasma, and a combination of both, and global performance assessed using the area under the receiver operator characteristic curve (AUC). Validation of urinary expression of miRNAs was performed on a further independent cohort of 36 patients.

Results

The best predictor in plasma using eight miRs yielded only moderate predictive performance (AUC = 0.62). The best predictor of high-risk disease was achieved using miR-16, miR-21 and miR-222 measured in urine (AUC = 0.75). This combination of three microRNAs in urine was a better predictor of high-risk disease than any individual microRNA. Using a different methodology we found that this set of miRNAs was unable to predict high-volume, high-grade disease.

Conclusions

Our initial findings suggested that plasma and urinary profiling of microRNAs at radical prostatectomy may allow prognostication of prostate cancer behaviour. However we found that the microRNA expression signature failed to validate in an independent cohort of patients using a different platform for PCR. This highlights the need for independent validation patient cohorts and suggests that urinary microRNA signatures at radical prostatectomy may not be a robust way to predict the course of clinical disease after definitive treatment for prostate cancer.     

Life expectancy estimates as a key factor in over-treatment: The case of prostate cancer

Objective: To estimate the magnitude of over-diagnosis and of potential and actual over-treatment regarding prostate cancer, taking comorbidities into account. Materials and methods: We used a sample collected by the French cancer registries of 1840 cases (T1: 583; T2: 1257) diagnosed in 2001. The proportion of over-diagnosed and over-treated patients was estimated by comparing life expectancy (LE), including or not comorbidities, with natural LE with cancer, using several assumptions from the literature. We distinguished potential and actual over-treatment according to the treatment that patients actually received. Results: Among patients with T1 tumors the proportion of potential over-treatment using LE adjusted for comorbidity varied from 29.5% to 53.5%, using LE adjusted on comorbidities, and varied from 9.3% to 22.2% regarding actual over-treatment. Between 7.7% and 24.4% of patient's receiving a radical prostatectomy, and between 30.8% and 62.5% of those receiving radiotherapy, were over-treated. Among patients with T2 tumors, the proportions of potential and actual over-treatment were 0.9% and 2.0%. Two per cent of patients receiving a radical prostatectomy and 4.9% of those receiving radiotherapy were over-treated. Comorbidities dramatically increased these proportions to nearly 100% of patients, with more than two comorbidities being potentially over-treated and around 33% actually over-treated. Conclusions: According to the French incidence, 3200–4800 French patients may be over-treated, among whom a large proportion of patients had comorbidities. The real issue is to offer the most appropriate treatment to people with low-grade tumors and comorbidities.     

Salvage cryosurgery of the prostate after radiation failure

Radiation therapy is one option for patients with localized prostate cancer. Despite advances in delivering radiation to the prostate gland with therapies such as brachytherapy and/or external beam radiation therapy, urologists will be faced with managing patients with rising prostate-specific antigen values and with positive biopsy results secondary to radiation-recurrent prostate cancer. If the cancer is detected early, salvage therapy can be initiated. Since salvage prostatectomy is associated with significant morbidity, patients are often left with the option of either watchful waiting or temporary palliation with hormone deprivation therapy, with its attendant toxicity. The introduction of third-generation cryotechnology using 17-gauge CryoNeedlestrade mark (Oncura, Inc., Plymouth Meeting, PA) and the recent modifications in the technique of salvage cryosurgery have enabled cryosurgeons to eradicate these tumors safely and with significantly decreased morbidity. Selection and management of patients, as well as the contemporary results of salvage cryosurgery, are discussed in this article.     

Radiation Therapy after Radical Prostatectomy for Prostate Cancer: Evaluation of Complications and Influence of Radiation Timing on Outcomes in a Large,Population-Based Cohort

PurposeTo evaluate the influence of timing of salvage and adjuvant radiation therapy on outcomes after prostatectomy for prostate cancer.MethodsUsing the Surveillance, Epidemiology, and End Results-Medicare linked database, we identified prostate cancer patients diagnosed during 1995–2007 who had one or more adverse pathological features after prostatectomy. The final cohort of 6,137 eligible patients included men who received prostatectomy alone (n = 4,509) or with adjuvant (n = 894) or salvage (n = 734) radiation therapy. Primary outcomes were genitourinary, gastrointestinal, and erectile dysfunction events and survival after treatment(s).ResultsRadiation therapy after prostatectomy was associated with higher rates of gastrointestinal and genitourinary events, but not erectile dysfunction. In adjusted models, earlier treatment with adjuvant radiation therapy was not associated with increased rates of genitourinary or erectile dysfunction events compared to delayed salvage radiation therapy. Early adjuvant radiation therapy was associated with lower rates of gastrointestinal events that salvage radiation therapy, with hazard ratios of 0.80 (95% CI, 0.67–0.95) for procedure-defined and 0.70 (95% CI, 0.59, 0.83) for diagnosis-defined events. There was no significant difference between ART and non-ART groups (SRT or RP alone) for overall survival (HR = 1.13 95% CI = (0.96, 1.34) p = 0.148).ConclusionsRadiation therapy after prostatectomy is associated with increased rates of gastrointestinal and genitourinary events. However, earlier radiation therapy is not associated with higher rates of gastrointestinal, genitourinary or sexual events. These findings oppose the conventional belief that delaying radiation therapy reduces the risk of radiation-related complications.     

Changes in prostate cancer at radical prostatectomy during the prostate specific antigen era: an Italian experience

OBJECTIVE: To assess changes in prostate cancer clinical and pathologic features by review of 15 years' experience with radical prostatectomy. STUDY DESIGN: A total of 596 consecutive patients who underwent open or laparoscopic radical prostatectomy (RP) between 1991 and 2006 were included. All had clinically localized prostate cancer. Surgical specimens were analyzed or blindly reviewed by a uropathologist, and whole-mount sections were prepared. Statistical analysis evaluated whether significant changes in clinical and pathologic variables occurred over time. RESULTS: Median prostate specific antigen (PSA) values at diagnosis significantly decreased over time. Definite stage migration was observed, with significant increase of organ-confined tumors. Incidence of seminal vesicle and lymph node involvement declined steadily. Median tumor volume decreased significantly over time (p<0.001). Incidence of nonsignificant cancers at RP increased significantly, reaching 25.6% in 2006. PSA value has progressively lost correlation with prostate cancer volume and today correlates only with prostate gland volume. CONCLUSION: Prostate cancer stage and volume at diagnosis have steadily decreased in the last 15 years, likely reflecting increasing use of PSA testing. In early prostate cancer, PSA level no longer correlates with tumor volume.     

The 4Kscore? Test Reduces Prostate Biopsy Rates in Community and Academic Urology Practices

There is significant concern regarding prostate cancer screening because of the potential for overdiagnosis and overtreatment of men who are discovered to have abnormal prostate specific antigen (PSA) levels and/or digital rectal examination (DRE) results. The 4Kscore® Test (OPKO Diagnostics, LLC) is a blood test that utilizes four kallikrein levels plus clinical information in an algorithm to calculate an individual’s percentage risk (< 1% to > 95%) for aggressive prostate cancer (Gleason score ≥ 7) on prostate biopsy. The 4Kscore Test, as a follow-up test after abnormal PSA and/or DRE test results, has been shown to improve the specificity for predicting the risk of aggressive prostate cancer and reduce unnecessary prostate biopsies. A clinical utility study was conducted to assess the influence of the 4Kscore Test on the decision to perform prostate biopsies in men referred to urologists for abnormal PSA and/or DRE results. The study population included 611 patients seen by 35 academic and community urologists in the United States. Urologists ordered the 4Kscore Test as part of their assessment of men referred for abnormal PSA and/or DRE test results. Results for the patients were stratified into low risk (< 7.5%), intermediate risk (7.5%–19.9%), and high risk (≥ 20%) for aggressive prostate cancer. The 4Kscore Test results influenced biopsy decisions in 88.7% of the men. Performing the 4Kscore Test resulted in a 64.6% reduction in prostate biopsies in patients; the actual percentage of cases not proceeding to biopsy were 94.0%, 52.9%, and 19.0% for men who had low-, intermediate-, and high-risk 4Kscore Test results, respectively. A higher 4Kscore Test was associated with greater likelihood of having a prostate biopsy (P < 0.001). Among the 171 patients who had a biopsy, the 4Kscore risk category is strongly associated with biopsy pathology. The 4Kscore Test, as a follow-up test for an abnormal PSA and/or DRE results, significantly influenced the physician and patient shared decision in clinical practice, which led to a reduction in prostate biopsies while increasing the probability of detecting aggressive cancer.Key Words: Prostate cancer, Prostate-specific antigen, Digital rectal examination, Biopsy rate, Gleason score, 4Kscore Test, Prostate cancer prognosisWidespread screening for prostate cancer with serum prostate-specific antigen (PSA) began in 1991, and subsequently a 45% decline in prostate cancer mortality has been observed.¹ A recent large European randomized clinical trial also reported a 29% reduction in death from prostate cancer in men undergoing routine screening.² However, because of a US study that showed no mortality benefits to organized PSA screening,³ and the net physical and psychologic burden of secondary adverse events triggered by PSA testing versus the number of lives saved, the United States Preventative Services Task Force (USPSTF) recently advised against routine PSA screening for prostate cancer.⁴ The concern of the USPSTF is based on the fact that most men diagnosed with prostate cancer have a tumor that is unlikely to pose a threat to life expectancy. A recent systematic analysis suggested that up to 60% of prostate cancers diagnosed in contemporary studies might be safely observed without a need for immediate intervention.⁵One of the primary challenges for urologists is the potential for under-grading of Gleason 6 prostate cancer due to biopsy sampling error; as a result, up to 90% of men with a Gleason 6 prostate cancer still proceed to prostate cancer treatment despite the advent of active surveillance programs. Approximately 66% of patients who are diagnosed with Gleason 6 disease at biopsy will be confirmed to have Gleason 6 cancer after radical prostatectomy.⁶ Some of these men are considered to have undergone overtreatment, because Gleason 6 cancer is not considered life threatening.⁷ This subset of men has the potential for developing complications following surgery, including erectile dysfunction, urinary incontinence, and changes in health-related quality of life with disruption of psychologic, sexual, and urinary function.^8–12The prostate biopsy procedure is invasive, and has significant costs and complications such as bleeding, urinary retention, and life-threatening infection. A recent population-based study from Ontario, Canada, revealed a fourfold increase to 4.1% for the rate of hospital admissions after prostate biopsy from 1996 to 2005, with 72% of admissions due to infection.¹³ These risks, combined with the anxiety involved in undergoing the procedure, present a significant burden to any man considering prostate cancer screening.The impact of the USPSTF has been a decrease in overall biopsy rates with a subsequent decline in the detection rate of Gleason 7 to 10 high-grade prostate cancers.¹⁴ The elimination of PSA screening means that the 20% to 30% of men who would have presented with an abnormal PSA level and been found to have high-grade prostate cancer may lose an opportunity for a possible cure.¹⁵ Clearly, there is a need for better risk-stratification tools for men presenting with an abnormal PSA level and/or digital rectal examination (DRE) result in order to both reduce the number of prostate biopsies performed and decrease the rate of Gleason 6 diagnosis and treatment.⁶The 4Kscore® Test (OPKO Diagnostics, LLC) incorporates measured blood levels of four kallikrein proteins: total PSA, free PSA, intact PSA, and human kallikrein 2 plus clinical information (age, DRE findings, and a history of prior negative biopsy result) into a proprietary algorithm to calculate an individual man’s percentage risk (< 1% to > 95%) of having Gleason score ≥ 7 if a prostate biopsy were to be performed. The 4Kscore Test has been extensively validated through a total of 12 prospective and retrospective studies published in peer-reviewed journals involving over 22,000 patients from both the United States and Europe.^16–23 These studies of men with elevated PSA levels involved cohorts of unscreened and screened men, and those with negative prior prostate biopsy results. Based on analyses published in these studies, the 4Kscore Test would have theoretically resulted in a 45% reduction in prostate biopsies while delaying the diagnosis of aggressive prostate cancer in only a few men (1.3%–4.7%).The 4Kscore Test is used to accurately determine percentage risk for aggressive prostate cancer (Gleason score ≥ 7) and provide additional information for men being considered for prostate biopsy because of abnormal PSA levels and/or DRE results. This allows urologists to better risk stratify men for biopsy and ultimately results in more selective treatment of those men with aggressive disease. Conversely, those men not harboring life-threatening disease are able to safely avoid prostate biopsy and overtreatment of indolent disease.With the introduction of any new diagnostic test such as the 4Kscore Test into clinical practice, it is important to assess whether its implementation, in this case as a follow-up test for an abnormal PSA and/or DRE result, influences and changes the physician-patient shared decision-making process and leads to an actual reduction in prostate biopsies. Herein we evaluated the influence of the 4Kscore Test on urologist-patient decisions about proceeding with biopsy in men who have an abnormal PSA and/or DRE result from multiple academic and community urology clinical practices in the United States.     

Prostate cancer in elderly men

Due to increasing life expectancy and the introduction of prostate-specific antigen (PSA) screening, a rising number of elderly men are diagnosed with prostate cancer. Besides PSA serum levels and Gleason score, age is considered to be a key prognostic factor in terms of treatment decisions. In men older than 70 years, treatment without curative intent may deprive the frail patient of years of life. Modern radical prostatectomy techniques are associated with low perioperative morbidity, excellent clinical outcome, and documented long-term disease control. Thus, radical prostatectomy should be considered because local treatment of organ-confined prostate cancer potentially cures disease. The huge extent of PSA screening programs may lead to overdiagnosis of prostate cancer. Not every man who is diagnosed with prostate cancer will develop clinically significant disease. This has led to the concept of expectant management for screen-detected, small-volume, low-grade disease, with the intention of providing therapy for those men with disease progression.     

DNA methylation profiles in African American prostate cancer patients in relation to disease progression

This study examined whether differential DNA methylation is associated with clinical features of more aggressive disease at diagnosis and prostate cancer recurrence in African American men, who are more likely to die from prostate cancer than other populations. Tumor tissues from 76 African Americans diagnosed with prostate cancer who had radical prostatectomy as their primary treatment were profiled for epigenome-wide DNA methylation levels. Long-term follow-up identified 19 patients with prostate cancer recurrence. Twenty-three CpGs were differentially methylated (FDR q ≤ 0.25, mean methylation difference ≥ 0.10) in patients with vs. without recurrence, including CpGs in GCK, CDKL2, PRDM13, and ZFR2. Methylation differences were also observed between men with metastatic-lethal prostate cancer vs. no recurrence (five CpGs), regional vs. local pathological stage (two CpGs), and higher vs. lower tumor aggressiveness (one CpG). These results indicate that differentially methylated CpG sites identified in tumor tissues of African American men may contribute to prostate cancer aggressiveness.     

The clinical burden of prostate cancer in Canada: forecasts from the Montreal Prostate Cancer Model

OBJECTIVES: The incidence of prostate cancer is increasing, as is the number of diagnostic and therapeutic interventions to manage this disease. We developed a Markov state-transition model--the Montreal Prostate Cancer Model--for improved forecasting of the health care requirements and outcomes associated with prostate cancer. We then validated the model by comparing its forecasted outcomes with published observations for various cohorts of men. METHODS: We combined aggregate data on the age-specific incidence of prostate cancer, the distribution of diagnosed tumours according to patient age, clinical stage and tumour grade, initial treatment, treatment complications, and progression rates to metastatic disease and death. Five treatments were considered: prostatectomy, radiation therapy, hormonal therapies, combination therapies and watchful waiting. The resulting model was used to calculate age-, stage-, grade- and treatment-specific clinical outcomes such as expected age at prostate cancer diagnosis and death, and metastasis-free, disease-specific and overall survival. RESULTS: We compared the model''s forecasts with available cohort data from the Surveillance, Epidemiology and End Results (SEER) Program, based on over 59,000 cases of localized prostate cancer. Among the SEER cases, the 10-year disease-specific survival rates following prostatectomy for tumour grades 1, 2 and 3 were 98%, 91% and 76% respectively, as compared with the model''s estimates of 96%, 92% and 84%. We also compared the model''s forecasts with the grade-specific survival among patients from the Connecticut Tumor Registry (CTR). The 10-year disease-specific survival among the CTR cases for grades 1, 2 and 3 were 91%, 76% and 54%, as compared with the model''s estimates of 91%, 73% and 37%. INTERPRETATION: The Montreal Prostate Cancer Model can be used to support health policy decision-making for the management of prostate cancer. The model can also be used to forecast clinical outcomes for individual men who have prostate cancer or are at risk of the disease.     

Regional trends in prostate cancer incidence,treatment with curative intent and mortality in Norway 1980–2007

Objectives: To compare the trends in prostate cancer incidence, treatment with curative intent and mortality across regions and counties in Norway, and to consider changes in incidence (an indicator for early diagnosis) and treatment with curative intent as explanatory factors for the decreasing prostate cancer mortality rates. Patients and methods: Prostate cancer incidence and mortality data (1980–2007) alongside treatment data (1987–2005) were obtained from the national, population-based Cancer Registry of Norway. Joinpoint regression models were fitted to age-adjusted incidence, treatment and mortality rates to identify linear changes in the trends. Results: Both age-adjusted incidence rates and rates of curative treatment of prostate cancer increased significantly in all five regions of Norway since the early 1990s. There was a strong positive correlation between increasing incidence and increasing use of curative treatment. The frequency of curative treatment in Western Norway was almost threefold that in the Northern and Central regions around year 2000. Subsequently, the regional trends converged and only minor differences in prostate cancer incidence and use of curative treatment were observed by 2005. The declines in mortality were observed earliest in the regions with the highest incidence and the most frequent use of curative treatment, while the largest decreases in mortality were found in counties where the largest increases in curative treatment were observed. Conclusions: The elucidation of the prostate cancer mortality trends is hindered by an inability to tease out the potential effects of early treatment from the more general impact of improved and more active treatment. However, it is likely that both sets of intervention have contributed to the decline in prostate cancer mortality in Norway since 1996.     

The effect of radiation therapy on post-prostatectomy urinary function

AimWe sought to evaluate the effect of radiation therapy on post-prostatectomy urinary quality of life in prostate cancer patients.BackgroundIn some men with non-metastatic prostate cancer, radiation therapy is indicated following prostatectomy. The radiation toxicity and quality of life considerations are unique in the post-prostatectomy setting.Materials and methodsA total of 106 patients receiving post-prostatectomy radiation therapy completed the Expanded Prostate Cancer Index Composite questionnaire before radiation and at 2-year follow-up. The primary outcomes of this study were the urinary domain summary score and subscale scores. Planned analysis was performed based on time interval from prostatectomy to radiation therapy.ResultsAmong the 106 patients analyzed, the mean urinary domain summary score worsened at 2-year follow-up after radiation therapy, lowering from 77.23–72.51 (p = 0.0085). Similar worsening was observed in the subscales of function (p = 0.003), bother (p = 0.0397), and incontinence (p = 0.0003). Urinary incontinence showed the greatest observable change among subscales. While the summary score worsened (p = 0.0031) among patients receiving radiation therapy more than 1 year after prostatectomy, it did not show statistically significant change in those treated 1 year or less after prostatectomy.ConclusionOur results demonstrate that post-prostatectomy radiation therapy is associated with modest declines in reportable urinary quality of life. Patients receiving radiation therapy more than 1 year after prostatectomy showed greater worsening of urinary quality of life, which indicates that there may be no functional advantage to delaying radiation therapy beyond the initial postoperative period.     

达芬奇机器人辅助腹腔镜下前列腺癌根治术的临床疗效及术后短期尿控恢复的影响因素分析

摘要 目的：观察达芬奇机器人辅助腹腔镜下前列腺癌根治术（RALRP）的临床疗效,并分析术后尿控恢复的影响因素。方法：选取2020年3月~2023年1月期间山东第一医科大学附属省立医院收治的腹腔镜下前列腺癌根治术182例作为研究对象,根据手术方式的不同将患者分为A组（n=81,传统腹腔镜前列腺癌根治术）和B组（n=101,RALRP）。记录两组手术时间、术后1个月的尿控率、术中出血量、住院时间、尿管拔除时间、引流管拔除时间、术后并发症的发生率。针对RALRP患者,多因素Logistic回归分析术后短期尿控恢复的影响因素。结果：B组手术时间、引流管拔除时间、尿管拔除时间、住院时间短于A组,术中出血量少于A组（P<0.05）。B组术后1个月的尿控率高于A组（P<0.05）。B组的术后并发症的发生率低于A组（P<0.05）。多因素Logistic回归分析结果显示,糖尿病、经尿道前列腺电切术（TURP）史是术后尿控恢复的危险因素,而规律提肛锻炼、保留神经血管束（NVB）是术后尿控恢复的保护因素（P<0.05）。结论：RALRP治疗前列腺癌患者,可缩短手术时间、引流管拔除时间、尿管拔除时间、住院时间,减少术中出血量,同时还可提高术后1个月的尿控率,降低并发症发生率。此外,糖尿病、规律提肛锻炼、保留NVB、TURP史等均是RALRP患者术后短期尿控恢复的影响因素,值得引起重视。