Prostate cancer trends in the era of prostate-specific antigen. An update of incidence,mortality, and clinical factors from the SEER database

Concurrent with the successful life-saving efforts in terms of prostate cancer diagnosis and treatment, some men who do not need treatment are receiving it. These are men destined to die of causes other than prostate cancer. Unfortunately, at diagnosis, men needing treatment for prostate cancer cannot be differentiated from men who do not. To make such decisions correctly for individual patients would require extremely precise measures of the time to death from prostate cancer versus when the patient would die from a competing cause. Predictive tools with this level of accuracy will never be available given the inherent uncertainty of life. At the time of prostate cancer diagnosis, the date and the cause of death for the patient are matters of weak statistical speculation. Unless the date of death from prostate cancer and the date of death from non-prostate cancer causes can be precisely determined for each patient, some men will always be overtreated or undertreated. Conservative strategies result in the undertreatment of some patients who would benefit from treatment while sparing other patients unneeded treatment. Aggressive strategies result in the overtreatment of patients who do not need therapy while curing other men of prostate cancer. Both strategies are correct, but only some of the time. Better methods of determining the length of life and cause of death may improve this situation, but not by much. [figure: see text] Dramatic shifts in the incidence, grade, stage, and age of men with prostate cancer have been observed with the advent of widespread PSA-based cancer detection in the United States. Grade and stage trends suggest that more biologically relevant (the shift from well-differentiated to moderately differentiated tumors) and yet therapeutically amenable (earlier stage) tumors have been identified in large numbers of patients during the PSA era. Clearly many men have been diagnosed and treated who will not benefit from such treatment. The relative mix of these two groups of men is not known. Given the long delay between treatment and mortality that is inherent in prostate cancer (Fig. 14), the full effects of treatment on prostate cancer mortality are probably not yet seen in prostate cancer mortality data.     

Commentary on “Initial management of prostate-specific antigen-detected,low-risk prostate cancer and the risk of death from prostate cancer.” Aizer AA,Chen MH,Hattangadi J,D'Amico AV. Harvard Radiation Oncology program,Boston, MA.: BJU Int 2013. doi: 10.1111/j.1464-410X.2012.11789.x. [Epub ahead of print]

WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: The recently published Prostate Cancer Intervention versus Observation Trial (PIVOT) did not identify differences in prostate cancer-specific mortality or all-cause mortality among patients with low-risk disease managed conservatively vs those managed definitively; however, recently published data suggest that older men may harbour more aggressive disease than is identified at biopsy owing to sampling error and undergrading. Whether older men with apparent low-risk disease are placed at risk of prostate cancer-specific mortality when managed conservatively remains unknown. The study used population-level data to show that non-curative approaches for older men with low-risk prostate cancer do result in an increased risk of prostate cancer-specific mortality. Differences between our study and the PIVOT trial include the fact that we included a larger sample size, analysed the data using an 'as-treated' approach, and included a healthier cohort of men as evinced by lower 4-year all-cause mortality estimates in our study than in the PIVOT. Our results suggest that older men with apparent low-risk prostate cancer are at risk of undergrading, which probably explains the differences in prostate cancer-specific mortality observed between men managed conservatively vs those managed definitively. Our study suggests that alternative approaches to excluding occult, high grade prostate cancer are needed in such men.ObjectiveTo evaluate whether older age in men with low-risk prostate cancer increases the risk of prostate cancer-specific mortality (PCSM) when non-curative approaches are selected as initial management.Patients and methodsThe study cohort consisted of 27 969 men, with a median age of 67 years, with prostate-specific antigen (PSA)-detected, low-risk prostate cancer (clinical category T1c, Gleason score≤6, and PSA≤10) identified by the Surveillance, Epidemiology and End Results programme between 2004 and 2007. Fine and Gray's competing risk regression analysis was used to evaluate whether management with non-curative vs curative therapy was associated with an increased risk of PCSM after adjusting for PSA level, age at diagnosis and year of diagnosis.ResultsAfter a median follow-up of 2.75 years, 1121 men died, 60 (5.4%) from prostate cancer. Both older age (adjusted hazard ratio [AHR] 1.05; 95% confidence interval (CI) 1.02-1.08; P<0.001) and non-curative treatment (AHR 3.34; 95% CI 1.97-5.67; P<0.001) were significantly associated with an increased risk of PCSM. Men>the median age experienced increased estimates of PCSM when treated with non-curative as opposed to curative intent (P<0.001); this finding was not seen in men≤the median age (P = 0.17).ConclusionPending prospective validation, our study suggests that non-curative approaches for older men with 'low-risk' prostate cancer result in an increased risk of PCSM, suggesting the need for alternative approaches to exclude occult, high grade prostate cancer in these men.     

Management of low (favourable)-risk prostate cancer

What's known on the subject? and What does the study add? Most men who are diagnosed with favourable‐risk prostate cancer undergo some form of active intervention, despite evidence that treatment will not improve health outcomes for many. The decision to undergo treatment after diagnosis is, in part, related to the inability to precisely determine the long‐term risk of harm without treatment. Nevertheless, physicians should consider patient age, overall health, and preferences for living with cancer and the potential side effects of curative treatments, before recommending a management option. This is especially important for older men, given the high level of evidence that those with low‐risk disease are unlikely to accrue any benefit from curative intervention. What is known on the subject: Over treatment of favourable‐risk prostate cancer is common, especially among older men. What does the study add: A review of the natural history of favourable‐risk prostate cancer in the context of choices for management of the disease. ? The management of favourable‐risk prostate cancer is controversial, and in the absence of controlled trials to inform best practice, choices are driven by personal beliefs with resultant wide variation in practice patterns. ? Men with favourable‐risk prostate cancer diagnosed today often undergo treatments that will not improve overall health outcomes. ? A shared‐decision approach for selecting optimal management of favourable‐risk disease should account for patient age, overall health, and preferences for living with cancer and the potential side effects of curative treatments.     

Prostate-specific antigen doubling time as a prognostic marker in prostate cancer

Prostate cancer has a varied natural history. Men with similar serum prostate-specific antigen (PSA) levels, clinical stages, and histologic features in their tissue specimens can have markedly different outcomes. While prostate cancer is lethal in some patients, most men die with cancer rather than because of it. Moreover, histologically apparent cancer can be found in the prostate glands of approximately 42% of men over 50 years of age who die from other causes, but the lifetime risk that a man in the US will be diagnosed with prostate cancer is estimated to be 11% and the risk of dying from the disease is only 3.1%. Consequently, appropriate disease management requires risk assessment. How likely is it that a given man's cancer will progress or metastasize over his remaining lifetime? What is the probability of successful treatment? What are the risks of adverse effects and complications of each treatment? Physicians use a variety of clinical and pathologic parameters to assess the risk that a given cancer poses to an individual patient. In addition to the accepted parameters of serum PSA level, clinical staging, and pathologic grading and staging, PSA doubling time has emerged as an important factor in the evaluation of men with newly diagnosed prostate cancer or prostate cancer that recurs after treatment. PSA doubling time can also be used as a surrogate marker for prostate cancer-specific death. This review summarizes current knowledge regarding the role of PSA doubling time as a prognostic marker in men with prostate cancer.     

Diabetes mellitus and health-related quality of life in prostate cancer: 5-year results from the Prostate Cancer Outcomes Study

Study Type – Therapy (outcomes research)
Level of Evidence 2b What’s known on the subject? and What does the study add? Comorbid diabetes can affect prostate cancer treatment decision‐making and outcomes. Few longitudinal studies have investigated the effect of comorbid diabetes on general and cancer‐specific health‐related quality of life (HRQL) in prostate cancer. Our study found that men with prevalent diabetes (pre‐prostate cancer diagnosis) generally had the poorest general HRQL, urinary control and sexual function scores over time, independent of treatment. Non‐diabetic men had the best scores and men with incident diabetes (post‐prostate cancer diagnosis) reported intermediate scores. OBJECTIVE ? To investigate the association between prostate cancer, diabetes, and long‐term general and cancer‐specific health‐related quality of life (HRQL) in a cohort of men with non‐metastatic prostate cancer. PATIENTS AND METHODS ? We used data from self‐administered surveys to assess the HRQL of men with localized or locally advanced disease at 6 (baseline), 12, 24, and 60 months after initial diagnosis. ? We examined changes in general and cancer‐specific HRQL with repeated measures analyses using a mixed‐model approach. RESULTS ? In total, we evaluated 1811 men, including 13% with prevalent (pre‐prostate cancer diagnosis) diabetes, 12% with incident (post‐prostate cancer diagnosis) diabetes, and 75% who never reported being diagnosed with diabetes. ? Generally, men with prevalent diabetes had the poorest scores on general HRQL and non‐diabetic men the best scores, independent of treatment. ? Similarly, men with prevalent diabetes had the lowest urinary control and sexual function scores over time, while men without diabetes had the highest scores. Men with incident diabetes reported intermediate scores. CONCLUSION ? Prostate cancer survivors with comorbid diabetes have poorer general and cancer‐specific HRQL than those without diabetes.     

The relationship between Prostate CAncer gene 3 (PCA3) and prostate cancer significance

Study Type – Diagnostic (exploratory cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Prior studies have shown that the PCA3 Score is indicative of prostate cancer significance and may aid in selecting men with clinically insignificant prostate cancer who could be candidates for active surveillance. This analysis of data from two studies enrolling 1,009 men shows that the PCA3 Score is associated with many biopsy and pathological features of the insignificant prostate cancer. The paper also provides guidance for the use of the PAC3 Assay in clinical practice.

OBJECTIVE

• ? To evaluate the relationship between Prostate CAncer gene 3 (PCA3) and prostate cancer significance.

PATIENTS AND METHODS

• ? Clinical data from two multi‐centre European open‐label, prospective studies evaluating the clinical utility of the PCA3 assay in guiding initial and repeat biopsy decisions were analysed.
• ? First‐catch urine was collected after digital rectal examination (three strokes per lobe) and the PCA3 score was determined using the PROGENSA® PCA3 assay.
• ? Transrectal ultrasound‐guided biopsy (≥8 cores) and radical prostatectomy (RP) specimens were analysed by the local pathologist. The relationship between biopsy and RP outcomes with the PCA3 score was assessed.

RESULTS

• ? Of the 1009 men enrolled, 348 (34%) had a positive biopsy. The median and mean PCA3 scores were statistically significantly lower in men with biopsy Gleason score <7 vs ≥7, with clinical stage T1c vs T2a–T2c, T3a cancers, with ≤33% vs >33% positive biopsy cores and with ‘biopsy indolent’ vs ‘biopsy significant’ prostate cancer (indolent prostate cancer defined by biopsy Epstein criteria).
• ? In all, 175 men with a positive biopsy had a RP: median and mean PCA3 scores were statistically significantly lower in men with pathological Gleason score <7 vs ≥7, and with pathological stage T2a–T2c vs T3a–T3b cancers.

CONCLUSIONS

• ? The PCA3 score may combined with traditional tools aid in identifying men with clinically insignificant prostate cancer, as shown by biopsy and RP pathological features including biopsy Epstein criteria, who could be candidates for active surveillance.
• ? Treatment selection should be based on a combination of clinical and pathological variables. If one wants to use a threshold point to guide treatment decisions in clinical practice, a PCA3 score threshold of 20 may have the highest utility for selecting men with clinically insignificant prostate cancer in whom active surveillance may be appropriate; a PCA3 score threshold of 50 may be used to identify men at high risk of harbouring significant prostate cancer who are candidates for RP.
• ? Although the association between the PCA3 score and prostate cancer aggressiveness needs further evaluation, the inclusion of the PCA3 score into patient management strategies may provide clinicians with another tool to more accurately determine the course of treatment.

     

Usefulness of prostate-specific antigen (PSA) rise as a marker of prostate cancer in men treated with dutasteride: lessons from the REDUCE study

Study Type – Prognostic (RCT) Level of Evidence 1b What's known on the subject? and What does the study add? Previous studies used the decrease in PSA after 6 months of dutasteride treatment as a new ‘baseline’ PSA value from which subsequent rises may serve as a warning for prostate cancer; however, PSA tends to continue to decrease as dutasteride treatment continues. By comparing positive biopsy rates in the REDUCE study using any rise from nadir in the dutasteride arm and standard PSA decision criteria (NCCN) in the placebo arm, we demonstrated that the ability to detect prostate cancer and high grade prostate cancer is maintained with dutasteride treatment.

OBJECTIVES

? To determine if dutasteride‐treated men can be monitored safely and adequately for prostate cancer based on data from the Reduction by Dutasteride in Prostate Cancer Events (REDUCE) study. ? To analyse whether the use of treatment‐specific criteria for repeat biopsy maintains the usefulness of prostate‐specific antigen (PSA) level for detecting high grade cancers.

PATIENTS AND METHODS

? The REDUCE study was a randomized, double‐blind, placebo‐controlled investigation of whether dutasteride (0.5 mg/day) reduced the risk of biopsy‐detectable prostate cancer in men with a previous negative biopsy. ? The usefulness of PSA was evaluated using biopsy thresholds defined by National Comprehensive Cancer Network guidelines in the placebo group and any rise in PSA from nadir (the lowest PSA level achieved while in the study) in the dutasteride group. ? The number of cancers detected on biopsy in the absence of increased/suspicious PSA level as well as sensitivity, specificity, positive predictive value and negative predictive value for high grade prostate cancer detection were analysed by treatment group. ? Prostate cancer pathological characteristics were compared between men who did and did not meet biopsy thresholds.

RESULTS

? Of 8231 men randomized, 3305 (dutasteride) and 3424 (placebo) underwent at least one prostate biopsy during the study and were included in the analysis. ? If only men meeting biopsy thresholds underwent biopsy, 25% (47/191) of Gleason 7 and 24% (7/29) of Gleason 8–10 cancers would have been missed in the dutasteride group, and 37% (78/209) of Gleason 7 and 22% (4/18) Gleason 8–10 cancers would have been missed in the placebo group. ? In both groups, the incidence of Gleason 7 and Gleason 8–10 cancers generally increased with greater rises in PSA. ? Sensitivity of PSA kinetics was higher and specificity was lower for the detection of Gleason 7–10 cancers in men treated with dutasteride vs placebo. ? Men with Gleason 7 and Gleason 8–10 cancer meeting biopsy thresholds had greater numbers of positive cores, percent core involvement, and biopsy cancer volume vs men not meeting thresholds.

CONCLUSION

? Using treatment‐specific biopsy thresholds, the present study shows that the ability of PSA kinetics to detect high grade prostate cancer is maintained with dutasteride compared with placebo in men with a previous negative biopsy. ? The sensitivity of PSA kinetics with dutasteride was similar to (Gleason 8–10) or higher than (Gleason 7–10) the placebo group; however, biopsy decisions based on a single increased PSA measurement from nadir in the dutasteride group resulted in a lower specificity compared with using a comparable biopsy threshold in the placebo group, indicating the importance of confirmation of PSA measurements.     

The effect of finasteride on prostate-specific antigen in men with benign prostatic hyperplasia

Finasteride is a specific 5-α-reductase inhibitor that has been shown to reduce prostate size and decrease serum levels of prostate specific antigen (PSA). Among men who received finasteride (5 mg/day) for 12 months in North American clinical trials and in whom prostate cancer was not diagnosed the median percentage change in PSA was ?50% (5–95% range: ?81% to + 20%). At baseline 72% had PSA ? 4.0 ng/ml and 93% had PSA ? 10.0 ng/ml. After 12 months on finasteride, 75% had PSA ? 2.0 ng/ml and 95% had PSA ? 5.0 ng/ml. Thus, the proportion of BPH patients with PSA levels of 2.0 ng/ml and 5.0 ng/ml after 12 months of treatment was comparable to the proportion with pretreatment PSA levels of 4.0 ng/ml and 10.0 ng/ml. Among the 10 men in these trials subsequently diagnosed with prostate cancer while on long-term finasteride therapy (5 mg/day), the median percentage change in PSA was ?26% (range: ?48% to + 12%). Limited experience with finasteride in men with prostate cancer suggests that the reduction in PSA of malignant origin appears to be no greater than the percentage reduction in PSA of benign origin. These effects on PSA have not been shown to confer any therapeutic benefit. Physicians using finasteride should be aware of its effect on PSA levels. © 1993 Wiley-Liss, Inc.     

Insignificant disease among men with intermediate-risk prostate cancer

Purpose

A paucity of data exists on the insignificant disease potentially suitable for active surveillance (AS) among men with intermediate-risk prostate cancer (PCa). We tried to identify pathologically insignificant disease and its preoperative predictors in men who underwent radical prostatectomy (RP) for intermediate-risk PCa.

Methods

We analyzed data of 1,630 men who underwent RP for intermediate-risk disease. Total tumor volume (TTV) data were available in 332 men. We examined factors associated with classically defined pathologically insignificant cancer (organ-confined disease with TTV ≤0.5 ml with no Gleason pattern 4 or 5) and pathologically favorable cancer (organ-confined disease with no Gleason pattern 4 or 5) potentially suitable for AS. Decision curve analysis was used to assess clinical utility of a multivariable model including preoperative variables for predicting pathologically unfavorable cancer.

Results

In the entire cohort, 221 of 1,630 (13.6 %) total patients had pathologically favorable cancer. Among 332 patients with TTV data available, 26 (7.8 %) had classically defined pathologically insignificant cancer. Between threshold probabilities of 20 and 40 %, decision curve analysis demonstrated that using multivariable model to identify AS candidates would not provide any benefit over simply treating all men who have intermediate-risk disease with RP.

Conclusion

Although a minority of patients with intermediate-risk disease may harbor pathologically favorable or insignificant cancer, currently available conventional tools are not sufficiently able to identify those patients.     

Ejaculatory disorders may affect screening for prostate cancer

PURPOSE: Ejaculatory disorders will be experienced in most men who are treated for localized prostate cancer. Baseline rates of ejaculatory disorders are unknown in men at risk for prostate cancer. Therefore, we explored the prevalence of those disorders and associated bother in men without evidence of prostate cancer who participated in an annual prostate cancer screening event. MATERIALS AND METHODS: A cohort of 1,273 men without clinical evidence of prostate cancer completed the self-administered Danish Prostate Symptom Score for sexual dysfunction. This questionnaire quantifies the rate of reduced ejaculatory volume, ejaculatory pain and the rate of coexistent erectile dysfunction. RESULTS: Mean age was 57.6 years (range 40 to 89). Of all men 46% (563) had reduced ejaculatory volume and 66% (356) of affected men were bothered by this condition. Ejaculatory pain was reported in 11% (134) and 89% (118) of these men reported associated bother. Finally, 45% (554) reported erectile dysfunction and 73% (403) reported associated bother. Reduced ejaculatory volume was associated with erectile dysfunction (p<0.001) and advanced age (p<0.001). Ejaculatory pain was not associated with one of these variables. CONCLUSIONS: Virtually all men will be affected by ejaculatory disorders after definitive treatment for localized prostate cancer. Therefore, it is important to observe that half of these individuals already have underlying reduced ejaculatory volume before treatment. Moreover, 1 of 10 men will be affected by ejaculatory pain. Both disorders are a significant source of bother and should be considered when treatment related quality of life is assessed.     

Managing benign prostatic hyperplasia and prostate cancer – the challenges today

Many men who reach average life expectancy will experience benign prostatic hyperplasia (BPH) or prostate cancer and together these conditions account for a considerable amount of ill-health and distress for men and their partners. Although there is considerable overlap across BPH and prostate cancer in symptom and risk profiles, management approaches are very different for each condition and appropriate diagnostic evaluation is therefore crucial to achieve the best possible outcome. The primary care physician should play a vital role in the diagnosis, management and appropriate referral of men with prostate disease with the ultimate goals being (1) early detection of prostate cancer and (2) effective treatment of benign prostate disease to manage symptoms and reduce the risk of progression.In prostate cancer, although there is debate over the implementation of systematic prostate-specific antigen (PSA) screening and appropriate thresholds, the use of PSA screening in conjunction with digital rectal examination (DRE) may aid earlier detection. The challenge is now to better determine which men are likely to develop aggressive disease so that overtreatment can be avoided. Results of large trials of systematic PSA screening are eagerly anticipated.In BPH, a major challenge is to identify men with bothersome lower urinary tract symptoms. Improved communication, education of patients, and the use of tools such as the International Prostate Symptom Score (IPSS) may help detect men who need treatment. Treatment selection should be driven by an understanding of the risks of disease progression, the impact of the disease on the patient's quality of life, and by the patient's own treatment preferences.Ultimately, we must empower our patients to make informed decisions about their diagnostic and treatment options through open dialogue and provision of appropriate information and education.     

Cardiovascular comorbidity and treatment regret in men with recurrent prostate cancer

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Treatment regret can have an adverse impact on a patient's overall outlook and has been associated with a poorer global quality of life. Understanding predictors of regret can help clinicians better counsel patients about their treatments so that later regret can be avoided. In previous studies, regret has been associated with lesser educational attainment, non‐White race, greater post‐treatment declines in sexual function and systemic symptoms. The present study found that, among men with recurrent prostate cancer, those with cardiovascular comorbidity were >50% more likely to regret their treatment choice than men without cardiovascular comorbidity. This study highlights the growing importance of considering comorbidity when counselling patients about prostate cancer treatment options, and provides a rationale for men with cardiovascular comorbidity to give additional consideration to active surveillance for their newly diagnosed prostate cancer.

OBJECTIVE

• ? To determine whether cardiovascular comorbidity is associated with increased treatment regret among men with recurrent prostate cancer.

METHODS

• ? The study cohort comprised 795 men in the Comprehensive, Observational, Multicenter, Prostate Adenocarcinoma (COMPARE) registry who experienced biochemical recurrence at a median (interquartile range) of 5.5 (2.8–9.1) years after prostatectomy (n= 410), external beam radiation therapy (n= 237), brachytherapy (n= 124) or primary androgen deprivation therapy (n= 24).
• ? Multivariable logistic regression analysis was used to determine whether cardiovascular comorbidity was associated with treatment regret.
• ? Cardiovascular comorbidity, which included myocardial infarction, congestive heart failure, angina, diabetes, stroke or circulation problems, was defined using a validated two‐question screening process after adjusting for sociodemographic and treatment factors and post‐treatment bladder and bowel toxicity.

RESULTS

• ? Of 795 men, 14.8% reported regret.
• ? Men with cardiovascular comorbidity were more likely to experience post‐therapy bowel toxicity (P= 0.022).
• ? In the adjusted multivariable model, the factors associated with increased treatment regret were: cardiovascular comorbidity (adjusted odds ratio [AOR]= 1.52 [95% CI:1.00–2.31], P= 0.048); younger age (AOR: 0.97 [95% CI 0.94–0.99] per year increase in age, P= 0.019); and bowel toxicity after treatment (AOR 1.58 [95% CI 1.03–2.43], P= 0.038).

CONCLUSIONS

• ? Among men with recurrent prostate cancer, those with cardiovascular comorbidity were >50% more likely to experience treatment regret than men without cardiovascular comorbidity.
• ? These data provide a rationale for men with cardiovascular comorbidity to give additional consideration to active surveillance for their newly diagnosed prostate cancer.

     

Cryosurgery for prostate cancer: new technology and indications

Patients diagnosed with prostate cancer who elect to pursue active treatment of their disease must choose among the many available treatment alternatives. Several treatment options now exist for similar-stage disease (clinical T1-3N0M0), including radical prostatectomy, external beam radiation, prostate brachytherapy (PB), and cryosurgical ablation of the prostate (CSAP). This article reviews the current role of CSAP in the treatment of clinically localized prostate cancer. CSAP has a role in the primary treatment of men with high-risk, clinically localized prostate cancer (defined as PSA >10, Gleason score ≥ 7, or clinical stage ≥ cT2B). CSAP (occasionally followed by external beam radiotherapy) appears to offer improved rates of cancer control over other types of single or combination therapies for this high-risk prostate cancer, and it is associated with an acceptable side-effect profile. CSAP should also be the treatment of choice for men with recurrent local disease who have undergone external beam radiotherapy or PB.     

Genome gender diversity in affected sib-pairs with familial vesico-ureteric reflux identified by single nucleotide polymorphism linkage analysis

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Despite a lack of randomised controlled trials, most men with locally advanced prostate cancer are recommended to undergo external beam radiotherapy (EBRT), often combined with long‐term androgen‐deprivation therapy (ADT). Many of these men are not offered radical prostatectomy (RP) by their treating urologist. Additionally, it is know that EBRT with long‐term ADT does provide good cancer control (88% at 10 years). We have previously published intermediate‐term follow‐up of a large series of men treatment with RP for cT3 prostate cancer. We report long‐term follow‐up of a large series of men treated with RP as primary treatment for cT3 prostate cancer. Our study shows that with long‐term follow‐up RP provides excellent oncological outcomes even at 20 years. While most men do require a multimodal treatment approach, many men can be managed successfully with RP alone.

OBJECTIVE

• ? To present long‐term survival outcomes after radical prostatectomy (RP) for patients with cT3 prostate cancer, as the optimal treatment for patients with clinical T3 prostate cancer is debated.

PATIENTS AND METHODS

• ? We identified 843 men who underwent RP for cT3 tumours between 1987 and 1997.
• ? Survival was estimated using the Kaplan–Meier method.
• ? Cox proportional hazards regression models were used to evaluate the association of clinicopathological features with outcome

RESULTS

• ? The median (range) postoperative follow‐up was 14.3 (0.1–23.5) years.
• ? Down‐staging to pT2 disease occurred in 26% (223/843) at surgery.
• ? Local recurrence‐free, systemic progression‐free and cancer‐specific survival for men with cT3 prostate cancer after RP was 76%, 72%, and 81%, respectively, at 20 years.
• ? On multivariate analysis, increasing RP Gleason score (hazard ratio [HR] 1.8; P= 0.01), non‐diploid chromatin content (HR 1.8; P= 0.01), positive surgical margins (HR 2.1; P= 0.007), and seminal vesicle invasion (HR 2.1; P= 0.005) were associated with a significant risk of prostate cancer death, while a more recent year of surgery was associated with a decreased risk of cancer‐specific mortality (HR 0.88; P= 0.01)

CONCLUSIONS

• ? RP affords accurate pathological staging and may be associated with durable cancer control for cT3 prostate cancer, with 20 years of follow‐up presented here.
• ? RP as part of a multimodal treatment strategy therefore remains a viable treatment option for patients with cT3 tumours.

     

The impact of social networks and partnership status on treatment choice in men with localized prostate cancer

Study Type – Decision analysis (cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Very little is known about prostate cancer decision‐making. Hence, marital status is often assumed a proxy for the amount of social support. While marital status is often used as a proxy for social support, we found that the quality of support may impact treatment type more than the extent of the social matrix.

OBJECTIVES

• ? To determine whether martial status and social support impact treatment choice.
• ? The decision to pursue radical prostatectomy for prostate cancer is often influenced by factors outside the realm of tumour risk, such as a man's support system at home.

PATIENTS AND METHODS

• ? We performed a retrospective cohort study of 418 low‐income men who were diagnosed with non‐metastatic prostate cancer and underwent definitive treatment with either radical prostatectomy or radiotherapy.
• ? We performed univariate and multivariate mixed‐effects logistic regression analysis, with the dependent variable being treatment type.
• ? Confidence intervals (CIs) for the predicted probabilities and relative risks were derived using bias‐corrected bootstrapping with 1000 repetitions.

RESULTS

• ? Men with two or more members in their support system were more likely to be older, Hispanic, have less than a high school education, earn more than US $1500 monthly, have high‐risk disease and be in a significant relationship.
• ? In multivariate analysis, partnered men with fewer than two social support members (relative risk, RR, 1.23; 95% CI, 1.02–1.63) were more likely to undergo surgery, whereas men who were morbidly obese (RR, 0.46; 95% CI, 0.09–0.88), high school graduates (RR, 0.80; 95% CI, 0.64–0.99) or had high‐risk disease (RR, 0.58; 95% CI, 0.44–0.85) were less likely to undergo surgery than their respective referent groups.
• ? Partnered men with two or more social support members were no more likely to undergo surgery than unpartnered men who lacked any social support.

CONCLUSIONS

• ? In the present study cohort, married men with fewer than two members in their social network were more likely to have undergone surgery.
• ? Although marital status is often used as a proxy for social support, we find that the quality of support and partner may impact treatment type more than the extent of the social matrix.

     

Umgang mit dem Prostatakarzinom bei über 75-j?hrigen M?nnern

Based on the exponential aging of the population and the increasing life expectancy in industrialized western countries, prostate cancer (PCa) in elderly men is becoming a disease of increasing significance. Consensus exists that men over the age of 75 years should not be screened for PCa; however, higher age as a single parameter should not exclude men from being diagnosed with prostate cancer and treated accordingly. It is well-known that overdiagnosis and overtreatment are frequent in this age group. Competing mortality risks of men older than 75 years may supersede the risk of dying from PCa several fold. Both the treating physician and the patient himself should therefore balance the possible risks and benefits of diagnosing and treating prostate cancer concerning the impact on quality of life. This is of special importance when taking into account that the complication rates of curative treatment modalities are higher in older patients than in younger men and that hormonal treatment might have negative effects especially in older men. Age, existing comorbidities, cognitive and physical status in combination with specific tumor parameters are useful tools for an individualized treatment. Therapy should be considered for healthy, active men aged 75 years or older who present with high-risk PCa and/or with a PSA doubling time <12 months. Elderly men who are unfit or have low to intermediate risk PCa will most likely not benefit from treatment.     

Is 'watchful waiting' a real choice for men with prostate cancer? A qualitative study

OBJECTIVE: To understand what leads men to choose 'watchful waiting' rather than active treatment for cancer of the prostate. PATIENTS AND METHODS: Fifty men with confirmed prostate cancer in England, Wales and Scotland were interviewed about all aspects of their illness, for a Database of Individual Patients' Experience of illness. The sample included men at different stages of diagnosis and with experience of a wide range of treatments. We report here only what men said about their choice of treatment and the decision-making process. RESULTS: Watchful waiting would have been clinically inappropriate for almost half of the men (those with serious urinary symptoms and those with metastatic disease). However, few of the men who might have chosen watchful-waiting remembered this being presented as a serious option. Most in this group chose radical prostatectomy, radiotherapy, brachytherapy or cryosurgery. The few who chose watchful waiting had found doctors who supported their decision, had assessed the evidence from Internet sites, and were concerned about the side-effects and uncertain outcome of treatment. Men who chose watchful waiting, as well as those who opted for treatment, described considerable pressure from family members, doctors or support groups, to seek active treatment. CONCLUSION: This study helps to explain why some men will not contemplate watchful waiting, and why others may find it difficult to pursue that option. Understanding men's concerns may help clinicians to support men's treatment decisions. Treatment for prostate cancer is highly controversial because no randomized, controlled trials have shown whether or not active intervention increases survival. If trials are not completed it cannot be determined whether active treatments are the best course of action for men with prostate cancer.     

Benign prostatic hyperplasia: racial differences in treatment patterns and prostate cancer prevalence

Study Type – Prevalence (prospective cohort with good follow‐up) Level of Evidence 1b What’s known on the subject? and What does the study add? Previous studies evaluating racial differences in BPH treatment and outcomes have concluded that more attention in the management of lower urinary tract symptoms should be directed at African Americans. Although the relationship between BPH and the development of prostate cancer is inconclusive, longitudinal studies have indicated racial disparities in the incidence of prostate cancer. This is the first long‐term follow‐up study in a BPH population to assess the incidence of prostate cancer among African American and Caucasian men under “real‐world” clinical practice circumstances. This study suggests that African Americans with BPH have a much greater risk of developing prostate cancer than similar Caucasian men, highlighting the need for education, prevention and early detection.

OBJECTIVE

? To compare prostate cancer, prostate‐related surgery and acute urinary retention rates, as well as associated healthcare resource use over 11 years in African American and Caucasian men with benign prostatic hyperplasia (BPH).

PATIENTS AND METHODS

? The BPH‐related medical and surgical charges and events were determined for 398 African American men and 1656 Caucasian men followed for a mean of 10.2 years within a health maintenance organization. ? Racial differences in clinical outcomes were evaluated using time‐to‐event analysis, stratifying results by baseline prostate‐specific antigen (PSA) values.

RESULTS

? Risk of a prostate cancer diagnosis was 2.2 times greater in African American than Caucasian men (95% CI 1.48–3.35, P < 0.001) in analyses adjusting for serum PSA level. ? Although African Americans were more likely to receive medical therapy for symptoms of BPH than Caucasians (43.5% vs 37.2%, respectively; P= 0.029), there were no clinically meaningful differences with respect to subsequent acute urinary retention or BPH‐related surgery between them, or BPH‐related medical charges (US $407 vs US $405 per month).

CONCLUSION

? As evidenced by this analysis of ‘real‐world’ clinical practice, African Americans with BPH have a much greater risk of developing prostate cancer than similar Caucasian men highlighting the need for education and early detection in this population.     

The role of transperineal template prostate biopsies in restaging men with prostate cancer managed by active surveillance

Study Type – Diagnostic (exploratory cohort) Level of Evidence 3b What's known on the subject? and What does the study add? The optimal method of active surveillance in prostate cancer remains unknown. This study is one of the first to report on the role of transperineal template prostate biopsies in active surveillance. It demonstrates that around one third of men are reclassified with more significant prostate cancer at an early stage in their management. This is a higher proportion than reported in contemporary cancers using standard transrectal biopsies for restaging.

OBJECTIVE

• ? To evaluate the role of transperineal template prostate biopsies in men on active surveillance.

PATIENTS AND METHODS

• ? In all, 101 men on active surveillance for prostate cancer underwent restaging transperineal template prostate biopsies at a single centre.
• ? Criteria for active surveillance were ≤75 years, Gleason ≤3+3, prostate‐specific antigen (PSA) ≤15 ng/mL, clinical stage T1–2a and ≤50% ultrasound‐guided transrectal biopsy cores positive for cancer with ≤10 mm of disease in a single core.
• ? The number of men with an increase in disease volume or Gleason grade on transperineal template biopsy and the number of men who later underwent radical treatment were assessed.
• ? The role of PSA and PSA kinetics were studied.

RESULTS

• ? In all, 34% of men had more significant prostate cancer on restaging transperineal template biopsies compared with their transrectal biopsies.
• ? Of these men, 44% had disease predominantly in the anterior part of the gland, an area often under‐sampled by transrectal biopsies.
• ? In the group of men who had their restaging transperineal template biopsies within 6 months of commencing active surveillance 38% had more significant disease.
• ? There was no correlation with PSA velocity or PSA doubling time.
• ? In total, 33% of men stopped active surveillance and had radical treatment.

CONCLUSIONS

• ? Around one‐third of men had more significant prostate cancer on transperineal template biopsies.
• ? This probably reflects under‐sampling by initial transrectal biopsies rather than disease progression.

     

Bicalutamide monotherapy preserves bone mineral density, muscle strength and has significant health-related quality of life benefits for osteoporotic men with prostate cancer

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? LH‐RH agonists, by suppressing testosterone and oestrogen, cause rapid bone demineralization and reduce both muscle strength and health related quality of life (HRQOL) in prostate cancer. A significant proportion of patients about to commence ADT are already osteoporotic, placing them at fracture risk. Bicalutamide monotherapy elevates testosterone and oestrogen levels, is licensed in locally advanced disease, but significantly underutilised in this setting. Whereas previous studies have assessed BMD and HRQOL in men across a range of BMDs, this study specifically evaluated osteoporotic men who are often older, with reduced muscle strength and with potentially the most to gain from bicalutamide monotherapy. BMD, muscle strength and HRQOL were each maintained across a 12‐month period, suggesting that this treatment option should be considered more often by physicians and patients counseled appropriately.

OBJECTIVES

? To evaluate changes in bone mineral density (BMD), body composition, muscle strength and health‐related quality of life (HRQL) during bicalutamide (150 mg) monotherapy in osteoporotic patients with non‐metastatic locally advanced prostate cancer. Osteoporosis is prevalent in men presenting with prostate cancer and also a common side effect of treatment with luteinizing hormone‐releasing hormone agonists, which are associated with decreased BMD and loss of lean body mass and suppress testosterone, unlike bicalutamide, which results in an increase in serum testosterone and oestrogen levels.

PATIENTS AND METHODS

? Forty‐two men with non‐metastatic locally advanced prostate cancer and osteoporosis (T‐score ≤?2.5) were treated with bicalutamide (150 mg) monotherapy. BMD was measured at baseline and 1 year. HRQL was assessed 3‐monthly using the RAND 36‐Item Health Survey and University of California Los Angeles Prostate Cancer Index questionnaires. Bone turnover markers, liver function tests, prostate‐specific antigen, testosterone, oestradiol and haemoglobin were measured at baseline, at 3 weeks and 3‐monthly thereafter. Arm anthropometry and dynamometry assessed fat mass, skeletal muscle mass and quadriceps strength.

RESULTS

? BMD was maintained (+2.1% lumbar spine, +1.2% total hip and +1.1% forearm). Prostate‐specific antigen decreased by 88% at 3 months. Testosterone and oestradiol had increased at 1 year by 58% and 42%, respectively. No increase in bone turnover markers was seen over 1 year. Quadriceps muscle strength was maintained. General and prostate cancer‐specific HRQL were maintained throughout the study, with no significant reductions in physical or sexual function. Adverse events included breast pain and gynaecomastia.

CONCLUSIONS

? Bicalutamide preserves BMD, muscle strength and HRQL in osteoporotic men with non‐metastatic locally advanced prostate cancer. It provides an alternative to medical castration for well informed men at high fracture risk and those wishing to retain physical and sexual activity, with luteinizing hormone‐releasing hormone agonists being reserved for those failing to respond or relapsing.