Prostate cancer

doi:10.1016/S0140-6736(08)60729-1

The Lancet

Volume 371, Issue 9625, 17–23 May 2008, Pages 1710-1721

https://doi.org/10.1016/S0140-6736(08)60729-1 Get rights and content

Summary

In developed countries, prostate cancer is the second most frequently diagnosed cancer, and the third most common cause of death from cancer in men. Apart from age and ethnic origin, a positive family history is probably the strongest known risk factor. Clinically, prostate cancer is diagnosed as local or advanced, and treatments range from surveillance to radical local treatment or androgen-deprivation treatment. Androgen deprivation reduces symptoms in about 70–80% of patients with advanced prostate cancer, but most tumours relapse within 2 years to an incurable androgen-independent state. The recorded incidence of prostate cancer has substantially increased in the past two decades, probably because of the introduction of screening with prostate-specific antigen, the use of improved biopsy techniques for diagnosis, and increased public awareness. Trends in mortality from the disease are less clearcut. Mortality changes are not of the same magnitude as the changes in incidence, and in some countries mortality has been stable or even decreased. The disparity between reported incidence and mortality rates leads to the probable conclusion that only a small proportion of diagnosed low-risk prostate cancers will progress to life-threatening disease during the lifetime of the patient.

Section snippets

Causes

Several studies have shown a familial aggregation of prostate cancer.1, 2, 3 One obvious possible reason for this aggregation is inheritance of genes that cause prostate cancer, some of which show high penetrance, whereas other genes show polymorphism and low penetrance. Some genes have been identified as potentially associated with prostate cancer. The first gene locus identified was named hereditary prostate cancer locus-1 (HPC1),⁴ for which RNASEL is the candidate allele.⁵ Since this

Epidemiology

Prostate cancer is the most common cancer in men in Europe, with about 190 000 new cases every year.35, 36 About 80 000 deaths a year result from this cancer in Europe.³⁷ Prostate-cancer mortality in the USA increased at a mean rate of 2·8% per year between 1988 and 1991, then decreased by 1·2% per year from 1991 to 1994 and more rapidly by 5·1% per year from 1994 to 1999.³⁸ By 1997, mortality rates in the USA for white men younger than 85 years were lower than those documented in 1986.38, 39 A

Screening

Several features (panel 1) raise the question of whether screening for prostate cancer is a suitable strategy to reduce mortality rates. In some parts of the world, screening programmes have been introduced, although no randomised controlled trials have been completed, to assess the effectiveness of such an approach. The reduction in mortality in the USA is frequently attributed to the widely adopted aggressive case-finding policy, although there is no proof that PSA screening is the reason for

Diagnosis

At present, diagnosis is based on examination of histopathological or cytological specimens from the gland. The most common way to obtain the necessary tissue specimen is by several systematic transrectal core biopsies, with guidance by transrectal ultrasound (figure 3). For many years, sextant biopsy was the standard procedure for the diagnosis of prostate cancer.⁵⁸ By directing the biopsy needle more laterally into the gland or increasing the number of cores to eight to 12, the detection rate

Prognostic factors

For patients with newly diagnosed prostate cancer, any information on the prognosis is much sought after. Generally, patients with a high tumour burden do poorly, whereas patients with a low tumour burden will do much better, irrespective of treatment regimen. In other words, the disease establishes the prognosis more than the choice of treatment. For patients with distant metastases (stage M1), the prognosis is poor, with an average survival of 24–48 months. The prognosis depends on the

Treatment of clinically localised prostate cancer

Localised prostate cancer is the most commonly diagnosed stage. The choice of treatment (active monitoring, radical prostatectomy, or any type of radiotherapy) is based on factors such as tumour characteristics and the patient's life expectancy. The reason why treatment with intent to cure is not used for all patients with prostate cancer is that many cases of highly to moderately differentiated prostate cancers have a very indolent course even when left without active treatment.84, 85 The high

Treatment with curative intent for locally advanced prostate cancer

Some patients with extracapsular extension of the tumour can still be offered treatment with curative intent. Radiotherapy has long been the standard option for these men. There are two main ways to increase the effectiveness of radiotherapy in men with locally advanced prostate cancer. First, dose escalation to greater than 70 Gy seems to result in good biochemical control rates, but survival advantages are yet to be seen.98, 99 Second, the outcome for these patients can be improved by the

Second-line treatment after failed primary surgery or radiotherapy

The first sign of failure after treatment with curative intent is generally a rising serum PSA concentration, occurring months to years before clinical symptoms or radiographic signs of recurrent disease. Thus, the choice of treatment for these men with rising PSA concentration after curative therapy is generally made without the contribution of any other objective signs of where the disease has recurred (ie, local or systemic failure). Generally, after either surgery or radiotherapy, local

Treatment of metastatic prostate cancer

Since the 1940s, androgen-ablative therapy has been the mainstay for management of advanced prostate cancer.¹⁰⁶ Patients for whom endocrine therapy is advisable are those with prostate cancer with extraprostatic growth, with or without lymph-node metastases, or cancer with distant metastases. Testicular androgens can be eliminated by surgical removal of the testicles, inhibition of pituitary secretion of luteinising hormone or follicle-stimulating hormone by downregulation of the

Treatment of hormone-refractory prostate cancer

The progression of metastatic androgen-independent prostate cancer is the final stage of this disease and constitutes a substantial threat of morbidity and mortality. For many years, cytotoxic chemotherapy was regarded as ineffective. However, two large clinical trials showed that docetaxel, alone or in combination with estramustine, improved the survival of men with hormone-refractory prostate cancer in comparison with mitoxantrone and corticosteroids.129, 130 These reports represent a new era

Complications of treatment

Panel 4 lists an overview of possible complications for the most common primary treatments of prostate cancer. The rate of complications is related to characteristics of the patient (eg, age, comorbidity, previous disturbances), the timing of the treatment although modern surgical and radiotherapeutic techniques have decreased the risk of complications substantially, and how the treatment was given: nerve-sparing versus non-nerve-sparing surgery, surgical approach, conformal versus

Conclusions

Nowadays, we can recognise patients with aggressive prostate cancer who will need some form of immediate therapy. These men include not only patients with advanced or metastatic stage disease but also those with clinically localised disease with aggressive features. The main difficulty that clinicians face is the large number of men diagnosed with early stage disease, of whom a small proportion will have disease progression and ultimately die from prostate cancer if not treated. Such

Search strategy and selection criteria

For patients with localised prostate cancer, we used meta-analyses and structured literature searches, and reviewed available publications in English. Some of the search terms were “prostate cancer” and “prostatic neoplasms”, from 2001 to 2004. For the other topics, we used guidelines from the European Association of Urology and the Swedish Board of Health and Welfare, which were based on meta-analyses. We referred to Cochrane reviews or other review articles, when relevant publications

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SeminarProstate cancer

Summary

Section snippets

Causes

Epidemiology

Screening

Diagnosis

Prognostic factors

Treatment of clinically localised prostate cancer

Treatment with curative intent for locally advanced prostate cancer

Second-line treatment after failed primary surgery or radiotherapy

Treatment of metastatic prostate cancer

Treatment of hormone-refractory prostate cancer

Complications of treatment

Conclusions

Search strategy and selection criteria

Lancet Oncol

Eur Urol

Lancet Oncol

J Urol

Ann Oncol

Eur Urol

J Urol

Eur Urol

J Urol

Urology

J Urol

Eur Urol

J Urol

J Urol

Urology

J Urol

J Urol

Int J Radiat Oncol Biol Phys

Lancet

Eur Urol

Europ J Cancer

Family history and the risk of prostate cancer

Prostate

Genetic epidemiology of prostate cancer in the Utah Mormon genealogy

Cancer Survey

Familial prostate cancer in Sweden. A nationwide register cohort study

Cancer

Major susceptibility locus for prostate cancer on chromosome 1 suggested by a genome-wide search

Science

Genetic analysis of the RNASEL gene in hereditary, familial, and sporadic prostate cancer

Clin Cancer Res

Genomics of prostate cancer: is there anything to “translate”?

Pathol Oncol Res

Prevalent mutations in prostate cancer

J Cell Biochem

Unravelling the genetics of prostate cancer

Am J Med Genet C Semin Med Genet

A common variant associated with prostate cancer in European and African populations

Nat Genet

Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer

Science

Description of the International Consortium for Prostate Cancer Genetics, and failure to replicate linkage of hereditary prostate cancer to 20q13

Prostate

The multiethnic cohort study: exploring genes, lifestyle and cancer risk

Nat Rev Cancer

Phyto-oestrogens and western diseases

Ann Med

Dietary survey of Finnish adults

A case-control study of prostate cancer in Japan: possible protective effect of traditional Japanese diet

Cancer Sci

Body size and prostate cancer: a 20-year follow-up study among 135 006 Swedish construction workers

J Natl Canc Inst

A review of physical activity and prostate cancer risk

Cancer Causes Control

Exercise and prostate cancer

Sports Med

Cigarette smoking and risk of prostate cancer in middle-aged men

Cancer Epidemiol Biomarkers Prev

The role of tomato products and lycopenes in the prevention of prostate cancer: a meta-analysis of observational studies

Cancer Epidemiol Biomarkers Prev

Selenium supplementation, base line plasma selenium status and incidence of prostate cancer: an analysis of the complete treatment period of the Nutritional prevention of cancer trial

BJU Int

Diet anthropometric measures and prostate cancer risk: a review of prospective cohort and intervention studies

BJU Int

Seminar
Prostate cancer