EAU guidelines on prostate cancer

OBJECTIVES: To present a summary of the 2007 version of the European Association of Urology (EAU) guidelines on prostate cancer (PCa). METHODS: A literature review of the new data emerging from 2004 to 2007 was performed by the working panel. The guidelines have been updated, and the level of evidence/grade of recommendation was added to the text based on a systematic review of the literature, which included a search of online databases and bibliographic reviews. RESULTS: A full version is available at the EAU Office or at www.uroweb.org. Systemic prostate biopsy under ultrasound guidance is the preferred diagnostic method. Active treatment is mostly recommended for patients with localized disease and a long life expectancy, with radical prostatectomy being shown to be superior to watchful waiting in a prospective randomized trial. Nerve-sparing radical prostatectomy represents the approach of choice in organ-confined disease; neoadjuvant androgen deprivation demonstrates no improvement of outcome variables. Radiation therapy should be performed with at least 72 and 78 Gy in low-risk and intermediate- to high-risk PCa, respectively. Monotherapeutic androgen deprivation is the standard of care in metastatic PCa; intermittent androgen deprivation might be an alternative treatment option for selected patients. Follow-up is largely based on prostate-specific antigen and a disease-specific history with imaging only indicated when symptoms occur. Cytotoxic therapy with docetaxel has emerged as the reference treatment for metastatic hormone-refractory PCa. CONCLUSIONS: The knowledge in the field of PCa is rapidly changing. These EAU guidelines on PCa summarize the most recent findings and put them into clinical practice.     

EAU Guidelines on Prostate Cancer. Part 1: Screening,Diagnosis, and Local Treatment with Curative Intent—Update 2013

Context

The most recent summary of the European Association of Urology (EAU) guidelines on prostate cancer (PCa) was published in 2011.

Objective

To present a summary of the 2013 version of the EAU guidelines on screening, diagnosis, and local treatment with curative intent of clinically organ-confined PCa.

Evidence acquisition

A literature review of the new data emerging from 2011 to 2013 has been performed by the EAU PCa guideline group. The guidelines have been updated, and levels of evidence and grades of recommendation have been added to the text based on a systematic review of the literature, which included a search of online databases and bibliographic reviews.

Evidence synthesis

A full version of the guidelines is available at the EAU office or online (www.uroweb.org). Current evidence is insufficient to warrant widespread population-based screening by prostate-specific antigen (PSA) for PCa. Systematic prostate biopsies under ultrasound guidance and local anesthesia are the preferred diagnostic method. Active surveillance represents a viable option in men with low-risk PCa and a long life expectancy. A biopsy progression indicates the need for active intervention, whereas the role of PSA doubling time is controversial. In men with locally advanced PCa for whom local therapy is not mandatory, watchful waiting (WW) is a treatment alternative to androgen-deprivation therapy (ADT), with equivalent oncologic efficacy. Active treatment is recommended mostly for patients with localized disease and a long life expectancy, with radical prostatectomy (RP) shown to be superior to WW in prospective randomized trials. Nerve-sparing RP is the approach of choice in organ-confined disease, while neoadjuvant ADT provides no improvement in outcome variables. Radiation therapy should be performed with ≥74 Gy in low-risk PCa and 78 Gy in intermediate- or high-risk PCa. For locally advanced disease, adjuvant ADT for 3 yr results in superior rates for disease-specific and overall survival and is the treatment of choice. Follow-up after local therapy is largely based on PSA and a disease-specific history, with imaging indicated only when symptoms occur.

Conclusions

Knowledge in the field of PCa is rapidly changing. These EAU guidelines on PCa summarize the most recent findings and put them into clinical practice.

Patient summary

A summary is presented of the 2013 EAU guidelines on screening, diagnosis, and local treatment with curative intent of clinically organ-confined prostate cancer (PCa). Screening continues to be done on an individual basis, in consultation with a physician. Diagnosis is by prostate biopsy. Active surveillance is an option in low-risk PCa and watchful waiting is an alternative to androgen-deprivation therapy in locally advanced PCa not requiring immediate local treatment. Radical prostatectomy is the only surgical option. Radiation therapy can be external or delivered by way of prostate implants. Treatment follow-up is based on the PSA level.     

EAU guidelines on prostate cancer. Part II: Treatment of advanced, relapsing, and castration-resistant prostate cancer

Objectives

Our aim is to present a summary of the 2010 version of the European Association of Urology (EAU) guidelines on the treatment of advanced, relapsing, and castration-resistant prostate cancer (CRPC).

Methods

The working panel performed a literature review of the new data emerging from 2007 to 2010. The guidelines were updated, and the levels of evidence (LEs) and/or grades of recommendation (GR) were added to the text based on a systematic review of the literature, which included a search of online databases and bibliographic reviews.

Results

Luteinising hormone-releasing hormone (LHRH) agonists are the standard of care in metastatic prostate cancer (PCa). Although LHRH antagonists decrease testosterone without any testosterone surge, their clinical benefit remains to be determined. Complete androgen blockade has a small survival benefit of about 5%. Intermittent androgen deprivation (IAD) results in equivalent oncologic efficacy when compared with continuous androgen-deprivation therapy (ADT) in well-selected populations. In locally advanced and metastatic PCa, early ADT does not result in a significant survival advantage when compared with delayed ADT. Relapse after local therapy is defined by prostate-specific antigen (PSA) values >0.2 ng/ml following radical prostatectomy (RP) and >2 ng/ml above the nadir after radiation therapy (RT). Therapy for PSA relapse after RP includes salvage RT at PSA levels <0.5 ng/ml and salvage RP or cryosurgical ablation of the prostate in radiation failures. Endorectal magnetic resonance imaging and ¹¹C-choline positron emission tomography/computed tomography (CT) are of limited importance if the PSA is <2.5 ng/ml; bone scans and CT can be omitted unless PSA is >20 ng/ml. Follow-up after ADT should include screening for the metabolic syndrome and an analysis of PSA and testosterone levels. Treatment of castration-resistant prostate cancer (CRPC) includes second-line hormonal therapy, novel agents, and chemotherapy with docetaxel at 75 mg/m² every 3 wk. Cabazitaxel as a second-line therapy for relapse after docetaxel might become a future option. Zoledronic acid and denusomab can be used in men with CRPC and osseous metastases to prevent skeletal-related complications.

Conclusion

The knowledge in the field of advanced, metastatic, and CRPC is rapidly changing. These EAU guidelines on PCa summarise the most recent findings and put them into clinical practice. A full version is available at the EAU office or online at www.uroweb.org.     

EAU Guidelines on Prostate Cancer. Part II: Treatment of Advanced,Relapsing, and Castration-Resistant Prostate Cancer

ObjectiveTo present a summary of the 2013 version of the European Association of Urology (EAU) guidelines on the treatment of advanced, relapsing, and castration-resistant prostate cancer (CRPC).Evidence acquisitionThe working panel performed a literature review of the new data (2011–2013). The guidelines were updated, and levels of evidence and/or grades of recommendation were added to the text based on a systematic review of the literature that included a search of online databases and bibliographic reviews.Evidence synthesisLuteinising hormone-releasing hormone (LHRH) agonists are the standard of care in metastatic prostate cancer (PCa). LHRH antagonists decrease testosterone without any testosterone surge, and they may be associated with an oncologic benefit compared with LHRH analogues. Complete androgen blockade has a small survival benefit of about 5%. Intermittent androgen deprivation results in noninferior oncologic efficacy when compared with continuous androgen-deprivation therapy (ADT) in well-selected populations. In locally advanced and metastatic PCa, early ADT does not result in a significant survival advantage when compared with delayed ADT. Relapse after local therapy is defined by prostate-specific antigen (PSA) values >0.2 ng/ml following radical prostatectomy (RP) and >2 ng/ml above the nadir and after radiation therapy (RT). Therapy for PSA relapse after RP includes salvage RT (SRT) at PSA levels <0.5 ng/ml and SRP or cryosurgical ablation of the prostate in radiation failures. Endorectal magnetic resonance imaging and 11C-choline positron emission tomography/computed tomography (PET/CT) are of limited importance if the PSA is <1.0 ng/ml; bone scans and CT can be omitted unless PSA is >20 ng/ml. Follow-up after ADT should include analysis of PSA and testosterone levels, and screening for cardiovascular disease and metabolic syndrome. Treatment of CRPC includes sipuleucel-T, abiraterone acetate plus prednisone (AA/P), or chemotherapy with docetaxel at 75 mg/m² every 3 wk. Cabazitaxel, AA/P, enzalutamide, and radium-223 are available for second-line treatment of CRPC following docetaxel. Zoledronic acid and denosumab can be used in men with CRPC and osseous metastases to prevent skeletal-related complications.ConclusionsThe knowledge in the field of advanced, metastatic, and castration-resistant PCa is rapidly changing. These EAU guidelines on PCa summarise the most recent findings and put them into clinical practice. A full version is available at the EAU office or at www.uroweb.org.Patient summaryWe present a summary of the 2013 version of the European Association of Urology guidelines on treatment of advanced, relapsing, and castration-resistant prostate cancer (CRPC).Luteinising hormone-releasing hormone (LHRH) agonists are the standard of care in metastatic prostate cancer (PCa). LHRH antagonists decrease testosterone without any testosterone surge, and they might be associated with an oncologic benefit compared with LHRH analogues. Complete androgen blockade has a small survival benefit of about 5%. Intermittent androgen deprivation results in noninferior oncologic efficacy when compared with continuous androgen-deprivation therapy (ADT) in well-selected populations. In locally advanced and metastatic PCa, early ADT does not result in a significant survival advantage when compared with delayed ADT. Relapse after local therapy is defined by prostate-specific antigen (PSA) values >0.2 ng/ml following radical prostatectomy (RP) and >2 ng/ml above the nadir and after radiation therapy. Therapy for PSA relapse after RP includes salvage radiation therapy at PSA levels <0.5 ng/ml and salvage RP or cryosurgical ablation of the prostate in radiation failures. Multiparametric magnetic resonance imaging and 11C-choline positron emission tomography/computed tomography (PET/CT) are of limited importance if the PSA is <1.0 ng/ml; bone scans, and CT can be omitted unless PSA is >20 ng/ml. Follow-up after ADT should include analysis of PSA and testosterone levels, and screening for cardiovascular disease and metabolic syndrome. Treatment of castration-resistant CRPC includes sipuleucel-T, abiraterone acetate plus prednisone (AA/P), or chemotherapy with docetaxel 75 mg/m² every 3 wk. Cabazitaxel, AA/P, enzalutamide, and radium-223 are available for second-line treatment of CRPC following docetaxel. Zoledronic acid and denosumab can be used in men with CRPC and osseous metastases to prevent skeletal-related complications.The guidelines reported should be adhered to in daily routine to improve the quality of care in PCa patients. As we have shown recently, guideline compliance is only in the area of 30–40%.     

EAU guidelines on prostate cancer. Part I: screening, diagnosis, and treatment of clinically localised disease

ObjectiveOur aim was to present a summary of the 2010 version of the European Association of Urology (EAU) guidelines on the screening, diagnosis, and treatment of clinically localised cancer of the prostate (PCa).MethodsThe working panel performed a literature review of the new data emerging from 2007 to 2010. The guidelines were updated, and level of evidence and grade of recommendation were added to the text based on a systematic review of the literature, which included a search of online databases and bibliographic reviews.ResultsA full version is available at the EAU office or Web site (www.uroweb.org). Current evidence is insufficient to warrant widespread population-based screening by prostate-specific antigen (PSA) for PCa. A systematic prostate biopsy under ultrasound guidance and local anaesthesia is the preferred diagnostic method. Active surveillance represents a viable option in men with low-risk PCa and a long life expectancy. PSA doubling time in < 3 yr or a biopsy progression indicates the need for active intervention. In men with locally advanced PCa in whom local therapy is not mandatory, watchful waiting (WW) is a treatment alternative to androgen-deprivation therapy (ADT) with equivalent oncologic efficacy. Active treatment is mostly recommended for patients with localised disease and a long life expectancy with radical prostatectomy (RP) shown to be superior to WW in a prospective randomised trial. Nerve-sparing RP represents the approach of choice in organ-confined disease; neoadjuvant androgen deprivation demonstrates no improvement of outcome variables. Radiation therapy should be performed with at least 74 Gy and 78 Gy in low-risk and intermediate/high-risk PCa, respectively. For locally advanced disease, adjuvant ADT for 3 yr results in superior disease-specific and overall survival rates and represents the treatment of choice. Follow-up after local therapy is largely based on PSA, and a disease-specific history with imaging is indicated only when symptoms occur.ConclusionsThe knowledge in the field of PCa is rapidly changing. These EAU guidelines on PCa summarise the most recent findings and put them into clinical practice.     

EAU guidelines on testicular cancer: 2011 update

Context

On behalf of the European Association of Urology (EAU), guidelines for the diagnosis, therapy, and follow-up of testicular cancer were established.

Objective

This article is a short version of the EAU testicular cancer guidelines and summarises the main conclusions from the guidelines on the management of testicular cancer.

Evidence acquisition

Guidelines were compiled by a multidisciplinary guidelines working group. A systematic review was carried out using Medline and Embase, also taking Cochrane evidence and data from the European Germ Cell Cancer Consensus Group into consideration. A panel of experts weighted the references, and a level of evidence and grade of recommendation were assigned.

Results

There is a paucity of literature especially regarding longer term follow-up, and results from a number of ongoing trials are awaited. The choice of treatment centre is of the utmost importance, and treatment in reference centres within clinical trials, especially for poor-prognosis nonseminomatous germ cell tumours, provides better outcomes. For patients with clinical stage I seminoma, based on recently published data on long-term toxicity, adjuvant radiotherapy is no longer recommended as first-line adjuvant treatment. The TNM classification 2009 is recommended.

Conclusions

These guidelines contain information for the standardised management of patients with testicular cancer based on the latest scientific insights. Cure rates are generally excellent, but because testicular cancer mainly affects men in their third or fourth decade of life, treatment effects on fertility require careful counselling of patients, and treatment must be tailored taking individual circumstances and patient preferences into account.     

EAU guidelines on urinary incontinence

Context

The first European Association of Urology (EAU) guidelines on incontinence were published in 2001. These guidelines were periodically updated in past years.

Objective

The aim of this paper is to present a summary of the 2009 update of the EAU guidelines on urinary incontinence (UI).

Evidence acquisition

The EAU working panel was part of the 4th International Consultation on Incontinence (ICI) and, with permission of the ICI, extracted the relevant data. The methodology of the 4th ICI was a comprehensive literature review by international experts and consensus formation. In addition, level of evidence was rated according to a modified Oxford system and grades of recommendation were given accordingly.

Evidence summary

A full version of the EAU guidelines on urinary incontinence is available as a printed document (extended and short form) and as a CD-ROM from the EAU office or online from the EAU Web site (http://www.uroweb.org/guidelines/online-guidelines/).The extent and invasiveness of assessment of UI depends on severity and/or complexity of symptoms and clinical signs and is different for men, women, frail older persons, children, and patients with neuropathy. At the level of initial management, basic diagnostic tests are applied to exclude an underlying disease or condition such as urinary tract infection. Treatment is mostly conservative (lifestyle interventions, physiotherapy, physical therapy, pharmacotherapy) and is of an empirical nature. At the level of specialised management (when primary therapy failed, diagnosis is unclear, or symptoms and/or signs are complex/severe), more elaborate assessment is generally required, including imaging, endoscopy, and urodynamics. Treatment options include invasive interventions and surgery.

Conclusions

Treatment options for UI are rapidly expanding. These EAU guidelines provide ratings of the evidence (guided by evidence-based medicine) and graded recommendations for the appropriate assessment and according treatment options and put them into clinical perspective.     

Clinical outcome of patients with lymph node positive prostate cancer after radical prostatectomy versus androgen deprivation

OBJECTIVE(S): To compare the outcome of patients with stage D1 (TxN+M0) prostate cancer undergoing radical prostatectomy or androgen deprivation alone. PATIENTS AND METHODS: Eighty-two patients treated for lymph node positive prostate cancer were retrospectively analyzed for time to progression, tumor-specific and overall survival. Furthermore, subsequent tumor and treatment related morbidity requiring intervention including frequency and duration of associated hospital stays was recorded. RESULTS: The extent of lymph node metastasis was significantly lower in 50 patients undergoing radical prostatectomy (+/- early androgen deprivation) compared to 32 receiving androgen deprivation only. The treatment groups, however, did not differ with regard to other characteristics including age, comorbidity, stage, grade and preoperative PSA. Mean actuarial progression-free, and tumor-specific survival was significantly longer for the radical prostatectomy patients (36% and 47%, respectively at 10 years) compared to androgen deprivation (15% and 32%, respectively). The latter group required more secondary interventions resulting in more frequent and overall longer hospital stays. CONCLUSIONS: Patients undergoing radical prostatectomy for stage D1 prostate cancer possibly benefit with regard to the necessity for secondary interventions and, at least for limited (solitary) nodal disease, in terms of progression-free and tumor-specific survival. However, the latter observation may be biased by a larger extent of lymph node metastasis in the androgen deprivation group.     

Treatment of muscle-invasive and metastatic bladder cancer: update of the EAU guidelines

Context

New data regarding treatment of muscle-invasive and metastatic bladder cancer (MiM-BC) has emerged and led to an update of the European Association of Urology (EAU) guidelines for MiM-BC.

Objective

To review the new EAU guidelines for MiM-BC with a specific focus on treatment.

Evidence acquisition

New literature published since the last update of the EAU guidelines in 2008 was obtained from Medline, the Cochrane Database of Systematic Reviews, and reference lists in publications and review articles and comprehensively screened by a group of urologists, oncologists, and a radiologist appointed by the EAU Guidelines Office. Previous recommendations based on the older literature on this subject were also taken into account. Levels of evidence (LEs) and grades of recommendations (GRs) were added based on a system modified from the Oxford Centre for Evidence-based Medicine Levels of Evidence.

Evidence synthesis

Current data demonstrate that neoadjuvant chemotherapy in conjunction with radical cystectomy (RC) is recommended in certain constellations of MiM-BC. RC remains the basic treatment of choice in localised invasive disease for both sexes. An attempt has been made to define the extent of surgery under standard conditions in both sexes. An orthotopic bladder substitute should be offered to both male and female patients lacking any contraindications, such as no tumour at the level of urethral dissection. In contrast to neoadjuvant chemotherapy, current advice recommends the use of adjuvant chemotherapy only within clinical trials. Multimodality bladder-preserving treatment in localised disease is currently regarded only as an alternative in selected, well-informed, and compliant patients for whom cystectomy is not considered for medical or personal reasons. In metastatic disease, the first-line treatment for patients fit enough to sustain cisplatin remains cisplatin-containing combination chemotherapy. With the advent of vinflunine, second-line chemotherapy has become available.

Conclusions

In the treatment of localised invasive bladder cancer (BCa), the standard treatment remains radical surgical removal of the bladder within standard limits, including as-yet-unspecified regional lymph nodes. However, the addition of neoadjuvant chemotherapy must be considered for certain specific patient groups. A new drug for second-line chemotherapy (vinflunine) in metastatic disease has been approved and is recommended.     

Use of Concomitant Androgen Deprivation Therapy in Patients Treated with Early Salvage Radiotherapy for Biochemical Recurrence After Radical Prostatectomy: Long-term Results from a Large,Multi-institutional Series

Background

Hormonal manipulation concomitant to salvage radiotherapy (SRT) given for biochemical recurrence (BCR) after radical prostatectomy (RP) improved outcomes in two randomized trials. However, neither of these studies focused on men treated at low prostate-specific antigen (PSA) levels.

Androgen and prostate cancer: the role of primary androgen deprivation therapy in localized prostate cancer

BackgroundThe basic mechanisms and clinical efficacy of primary androgen deprivation therapy (PADT), especially combined androgen blockade (CAB) for localized or locally advanced prostate cancer (PCa) have been outlined. An important point relates to which patients are suitable candidates for PADT.MethodsA retrospective review of the efficacy of PADT in 628 patients with localized or locally advanced PCa treated with PADT at seven institutions in Japan was carried out.ResultsIt was found that more than 30% of low- or intermediate-risk localized PCa patients could have their disease controlled over the long-term by PADT alone. Short-term or intermittent PADT could not be recommended because of the possibility of character change in the cancer cells as a result of incomplete androgen ablation.ConclusionAlgorithms are proposed for the treatment of localized PCa not only in low- and intermediate-risk groups, but also in the high-risk group. Future research directions are indicated.     

Substratification of high-risk localised prostate cancer treated by radical prostatectomy

AIM: To evaluate the clinical outcome of high-risk prostate cancer (PC) treated by radical prostatectomy (RP) according to risk factors. METHODS: Patients with stage cT1-T3 PC were stratified in high and low/intermediate risk groups using D'Amico's criteria: PSA>or=20 ng/ml or Gleason score>or=8 or clinical stage>or=T2c. The Kaplan Meier and Log rank test were used to generate estimates of biochemical free-survival (BFS) and PC specific mortality (PCSM). RESULTS: We analysed 1,109 patients with a median age of 64.1 years, a mean PSA of 12.8 and a median follow-up of 8.18 years (max. 17.5 years). Overall PSA failures (PSAF) were observed in 23.4%, mortality by all causes in 11.4% and PCSM in 2.9%. The 10-year BFS of the 290 high-risk was 45 versus 75.5% for low/intermediate risk patients and the 10-year PCSM was 10.3 versus 1.4%, respectively. Of the 290 high-risk PC, 25% had organ-confined disease at surgery with 28% PSAF compared to 55% PSAF for non-organ-confined PC irrespective of nodal status. High-risk patients with 1 or>or=2 high risk criteria had 2.6 and 3.86 times increased risk of PSAF compared to low/intermediate risk. Ten-year PCSM for PC individual risk criteria was 4.5% for PSA>or=20, 9.2% for stage>or=T2c and 18.2% for Gleason>or=8. CONCLUSION: Patients with high-risk PC treated by RP by experienced surgeons can have a favourable long-term survival. Further substratification should take into account the variable prognostic implication of the different individual risk factors.     

Cardiovascular risk with androgen deprivation therapy for prostate cancer: Potential mechanisms

Androgen deprivation therapy (ADT) is frequently used for the treatment of advanced prostate cancer. ADT is associated with numerous side effects related to its mode of action, namely the suppression of testosterone to castrate levels. Recently, several large retrospective studies have also reported an increased risk of diabetes and cardiovascular disease in men receiving ADT, although these risks have not been confirmed by prospective randomized trials. We review the literature to consider the risk of cardiovascular disease with different forms of ADT and examine in detail potential mechanisms by which any such risk could be mediated. Mechanisms discussed include the metabolic syndrome resulting from low testosterone level and the potential roles of testosterone flare, gonadotropin-releasing hormone receptors outside the pituitary gland, and altered levels of follicle-stimulating hormone. Finally, the clinical implications for men prescribed ADT for the treatment of advanced prostate cancer are considered.     

High-risk prostate cancer: from definition to contemporary management

Context

High-risk prostate cancer (PCa) is a potentially lethal disease. It is clinically important to identify patients with high-risk PCa early on because they stand to benefit the most from curative therapy. Because of recent advances in PCa management, a multimodal approach may be advantageous.

Objective

Define high-risk PCa, and identify the best diagnostic and treatment patterns for patients with clinically localized and locally advanced disease. A critical analysis of published results following monomodal and/or multimodal therapy for high-risk PCa patients was also performed.

Evidence acquisition

A review of the literature was performed using the Medline, Embase, Scopus, and Web of Science databases as well as the Cochrane Database of Systematic Reviews.

Evidence synthesis

High-risk PCa accounts for ≤15% of all new diagnoses. Compared with patients with low- and intermediate-risk PCa, patients with high-risk PCa are at increased risk of treatment failure. Unfortunately, no contemporary randomized controlled trials comparing different treatment modalities exist. Evaluation of the results published to date shows that no single treatment can be universally recommended. Most often, a multimodal approach is warranted to optimize patient outcomes.

Conclusions

A significant minority of patients continue to present with high-risk PCa, which remains lethal in some cases. Outcomes following treatment of men with high-risk tumors have not substantially improved over time. However, not all high-risk patients are at the same risk of PCa progression and death. At present, a multimodal approach seems the best way to achieve acceptable outcomes for high-risk PCa patients.     

Optimal timing of early versus delayed adjuvant radiotherapy following radical prostatectomy for locally advanced prostate cancer

ObjectivesAlthough post–radical prostatectomy (RP) adjuvant radiation therapy (ART) benefits disease that is staged as pT3 or higher, the optimal ART timing remains unknown. Our objective is to characterize the outcomes and optimal timing of early vs. delayed ART.Materials and methodsFrom the Surveillance, Epidemiology and End Results-Medicare data from 1995 to 2007, we identified 963 men with pT3N0 disease receiving early (<4 mo after RP, n = 419) vs. delayed (4–12 mo after RP, n = 544) ART after RP. Utilizing propensity score methods, we compared overall mortality, prostate cancer–specific mortality (PCSM), bone-related events (BRE), salvage hormonal therapy utilization, and intervention for urethral stricture. We then used the maximal statistic approach to determine at what time post-RP ART had the most significant effect on outcomes of interest in men with pT3N0 disease.ResultsWhen compared with delayed ART in men with pT3 disease, early ART was associated with improved PCSM (0.47 vs. 1.02 events per 100 person-years; P = 0.038) and less salvage hormonal therapy (2.88 vs. 4.59 events per 100 person-years; P = 0.001). Delaying ART beyond 5 months is associated with worse PCSM (hazard ratio [HR] 2.3; P = 0.020), beyond 3 months is associated with more BRE (HR 1.6; P = 0.025), and beyond 4 months is associated higher rates of salvage hormonal therapy (HR 1.6; P = 0.002). ART performed after 9 months was associated with fewer urethral strictures (HR 0.6; P = 0.042).ConclusionInitiating ART less than 5 months after RP for pT3 is associated with improved PCSM. Early ART is also associated with fewer BRE and less use of salvage hormonal therapy if administered earlier than 3 and 4 months after RP, respectively. However, ART administered later than 9 months after RP is associated with fewer urethral strictures. Our population-based findings complement randomized trials designed with fixed ART timing.     

Optimal treatment of locally advanced prostate cancer

The treatment of clinically locally advanced prostate cancer (cT3–4) is subject to controversies. Patients with lymph node metastases as well as patients with overstaged localized and thus curable disease fall into this category. Radical prostatectomy, external beam radiotherapy and early or deferred hormonal therapy are possible treatment options. Multimodal treatment (i.e., a combination of these options) is frequently used. After radical prostatectomy, Gleason score-adjusted disease-specific survival does not differ meaningfully between the tumor stages pT2 and pT3–4. In the case of lymph node metastases after radical prostatectomy, but not in node-negative disease, adjuvant hormonal treatment seems to improve survival. Adjuvant radiotherapy may improve biochemical and local control in locally advanced prostate cancer, a survival benefit has, however, not yet been proven. External beam radiotherapy alone provides unfavourable survival rates in locally advanced prostate cancer. Adjuvant hormonal treatment may improve outcome in this setting. When no curative treatment is chosen, early hormonal treatment seems to provide modest benefit compared with deferred therapy.     

New treatment approaches for prostate cancer based on peptide analogues

OBJECTIVES: New therapy modalities for the treatment of advanced prostate cancer based on peptide analogues are reviewed. RESULTS: Agonists and antagonists of luteinising hormone-releasing hormone (LHRH) lead to androgen deprivation, but direct effects on tumours may also play a role. Radiolabeled somatostatin analogues can be targeted to tumours expressing receptors for somatostatin and have been successfully applied for the localization of these tumours. Tumoural LHRH, growth hormone-releasing hormone (GHRH), and bombesin/gastrin-releasing peptide (BN/GRP) and their receptors appear to be involved in the proliferation of prostate cancer. On the basis of the recent advances in the understanding of the role of neuropeptides in tumour growth and progression, new therapeutic modalities are being developed that are based on antagonists of GHRH and of BN/GRP, which inhibit growth factors or their receptors. Another promising approach for the therapy of prostate cancer consists of the use of cytotoxic analogues of LHRH, bombesin, and somatostatin, which can be targeted to receptors for these peptides in prostate cancers and their metastases. CONCLUSIONS: New promising forms of hormone therapy and targeted chemotherapy may improve therapy of advanced stage prostate cancer.     

Secondary therapy, metastatic progression, and cancer-specific mortality in men with clinically high-risk prostate cancer treated with radical prostatectomy

OBJECTIVES: Commonly used definitions for high-risk prostate cancer identify men at increased risk of PSA relapse after radical prostatectomy (RP). We assessed how accurately these definitions identify patients likely to receive secondary cancer therapy, experience metastatic progression, or die of prostate cancer. MATERIALS AND METHODS: Among 5960 men with clinically localized or locally advanced prostate cancer who underwent RP, we identified eight different high-risk subsets, each comprising 4-40% of the study population. Estimates of freedom from radiation therapy, hormonal therapy, and metastatic progression after surgery were generated for each high-risk cohort with the Kaplan-Meier method, and hazard ratios (HR) were calculated with a Cox proportional hazards regression. The cumulative incidence and HR for prostate cancer-specific mortality (PCSM) were estimated with competing risk analysis. RESULTS: Each of the studied high-risk criteria was associated with increased hazard of secondary cancer therapy (HR=1.3-5.2, p<0.05) and metastatic progression (HR=2.1-6.9, p<0.05). However, depending on the definition, the probability of freedom from additional therapy 10 yr after surgery ranged from 35% to 76%. The 10-yr cumulative incidence of PCSM in high-risk patients ranged from 3% to 11% (HR=3.2-10.4, p<0.0005). CONCLUSIONS: Commonly used definitions for high-risk prostate cancer identify men at increased risk of secondary cancer therapy, metastatic progression, and PCSM following RP. However, a substantial proportion of high-risk patients remain free from additional therapy or metastatic disease many years after surgery. The risk of PCSM within 10 yr of treatment is remarkably low, even for patients at the highest risk of recurrent disease.