Материал: Oxford American Handbook of Urology ( PDFDrive )

192 CHAPTER 6 Urological neoplasia

Prostate cancer: incidence, prevalence, and mortality

Incidence

The widespread use of prostatic-specific antigen (PSA)-based screening led to a sharp increase in the incidence of prostate cancer that peaked the early 1990s in the United States.

In 2010 men were diagnosed with prostate cancer in the United States. This exceeds the number of men diagnosed with lung cancer (116,759), placing prostate cancer as the most commonly diagnosed male cancer (excluding basal and squamous cell skin cancers). It accounts for about 33% of all male cancers diagnosed.

Prevalence

Currently, it is estimated that a man in the United States has a 1 in 6 (16.6%) lifetime risk of being diagnosed with prostate cancer as a result of clinical symptoms, signs, or PSA testing. However, the true prevalence of the disease is hinted at by postmortem studies carried out on men who have died of other causes.

There is a significant number of men with so-called autopsy cancers. This concept of latent prostate cancer—a biologically nonaggressive and slow-growing form of the disease, may be unnecessarily detected by aggressive PSA screening (p. 216).

Mortality

It is estimated that prostate cancer accounts for 9% of male cancer deaths. Mortality increased slowly in the UK and United States during the 1970s and 1980s, peaking in the 1990s and slowly decreasing thereafter. Mortality has declined 4% per year between 1999 and 2003.

In 2009, 27,360 deaths were attributed to prostate cancer in the United States, the second-most common form of male cancer death. This compares with 25,240 deaths due to colorectal cancer and 88,900 due to lung cancer.

The explanation for the reduced prostate cancer mortality is highly controversial. The potential reasons for this decline include improved diagnosis and treatment of localized disease, the early use of hormonal therapy, and PSA-based screening.

The concept of screening for prostate cancer detecting earlier stages and possibly more curable disease remains highly controversial, with various studies supporting and refuting the effectiveness of screening based on PSA testing and rectal examination (see p. 194).

PROSTATE CANCER PATHOLOGY: PREMALIGNANT LESIONS 193

Prostate cancer pathology: premalignant lesions

Two histological lesions are currently regarded as either premalignant or “perimalignant” (related to the presence of cancer)—prostatic intraepithelial neoplasia (PIN) and atypical small acinar proliferation (ASAP).

Prostatic intraepithelial neoplasia

PIN consists of architecturally benign prostatic acini and ducts lined by cytologically atypical cells and confined within the epithelium. The basal cell layer is present, although the basement membrane may be fragmented.

PIN was formerly known as ductal dysplasia or reported by pathologists as “suspicious for cancer.” PIN was classified into low-grade (mild) and high-grade (moderate to severe) forms, based on the presence of prominent nucleoli. Subsequently, pathologists have agreed to report only highgrade PIN, since low-grade PIN has no prognostic value.

High-grade PIN is believed by many to be to be a precursor to intermediateor high-grade prostate cancer and its finding in sextant peripheral zone prostate biopsies carries a 30–40% prediction of prostate cancer at subsequent biopsy. However, with the widespread use of more extensive biopsy protocols, the significance of isolated high-grade PIN has become less clear.

High-grade PIN is reported in 5–10% of prostate needle biopsies. It does not appear to affect the serum PSA value. The site of the PIN is not indicative of the site of subsequently diagnosed cancer, nor is PIN always present in a prostate containing cancer.

Most authors recommended that repeat systematic biopsies be performed in 3–6 months if multifocal high-grade PIN is reported on initial needle biopsy or transurethral resection of the prostate (TURP). Studies also suggest that a repeat biopsy may be unnecessary in the setting of isolated high-grade PIN without other clinical indicators of cancer.

Atypical small acinar proliferation

ASAP is a histological finding suggesting that a focus of atypical glands is suspicious for cancer. ASAP and HGPIN are distinct entities and the two should not be used interchangeably. The ASAP acini are small, lined with cytologically abnormal epithelial cells. The columnar cells have prominent nuclei containing nucleoli, while the basal layer may be focally absent. The basement membrane is intact.

Prostate cancer has been identified in specimens from subsequent biopsies in up to 60% of cases of ASAP, indicating that this finding is a significant predictor of cancer. Identification of ASAP (with or without high-grade PIN) warrants repeat biopsy for concurrent or subsequent invasive prostate carcinoma.

194 CHAPTER 6 Urological neoplasia

Prostatic-specific antigen (PSA) and prostate cancer screening

Screening men aged 50–70 years with PSA and digital rectal examination (DRE), and subsequent early detection and treatment, may reduce the significant mortality and morbidity caused by prostate cancer. Supporters of screening say these acceptable and relatively inexpensive tests will detect clinically significant disease before it leaves the prostate.

The lead time, estimated at 6–12 years, between the screened diagnosis and the clinical diagnosis should enable more organ-confined cancers to be diagnosed and cured. However, because of the low specificity of PSA (40%) and the high prevalence of latent or autopsy prostate cancer, opponents argue that many men would suffer unnecessary anxiety, biopsies, overdiagnosis (25–50%), and overtreatment.

Two long-awaited screening studies were reported in 2009 with conflicting data. The U.S. PLCO (Prostate Lung Colorectal and Ovarian) screening study did not demonstrate a reduction in prostate cancer mortality.1 However, the study was considered “contaminated” by many, as a large number of men were prescreened and the control group was contaminated by this screening outside of the study. The ERSPC (European Randomized Study of Screening for Prostate Cancer) trial demonstrated a 20% reduction in mortality and a 25% reduction in metastatic disease due to screening.2

Decisions regarding early detection of prostate cancer should be individualized, and benefits and consequences should be discussed with the patient before PSA testing occurs. Not all men are appropriate candidates for screening efforts for this disease. Ideally, physicians should consider a number of factors, including patient age and comorbidity, as well as preferences for the relevant potential outcomes.

The practice of screening in men with less than a 10-year life expectancy (due to age or comorbidity) should generally be discouraged.4 Informed consent prior to PSA testing has been recommended by some groups. The American Urological Association (AUA) 2009 guideline recommends that early detection and risk assessment of prostate cancer be offered to asymptomatic men 40 years of age or older who wish to be screened and have an estimated life expectancy of more than 10 years.

If the patient and clinician are interested in the best objective data on determining the risk of biopsy-detectable prostate cancer, the National Cancer Institute (NCI) has published a risk calculator3 based on the Prostate Cancer Prevention Trial.

1 Andriole G, et al. (2009). Mortality results from a randomized prostate-cancer screening trial. N Engl J Med 360:1310–1319.

2 Schröder F, et al. (2009). Screening and prostate-cancer mortality in a randomized European study. N Engl J Med 360:1320–1328.

3 Available at: http://deb.uthscsa.edu/URORiskCalc/Pages/uroriskcalc.jsp. (Accessed July 2009). Race, age, PSA level, family history, prior prostate biopsy, and the use of finasteride are factors that are entered into the system.

4 Smith, RA, et al (2010). Cancer Screening in the United States, 2010: A Review of Current American Cancer Society Guidelines and Issues in Cancer Screening CA Cancer J Clin 60:70–98.

COUNSELING BEFORE PROSTATE CANCER SCREENING 195

Counseling before prostate cancer screening

Discussing the risks and benefits of prostate cancer screening is considered mandatory before offering a PSA and DRE to asymptomatic men. Such counseling is less controversial when evaluating a symptomatic patient, because a diagnosis of prostate cancer could alter the management. However, all patients should be informed when PSA testing is being considered.

The following points should be considered when counseling asymptomatic men:

•Cancer will be identified in up to 5% men screened.

•Screening enables earlier cancer detection and has the potential to decrease mortality rates.

•Early detection and treatment may avoid future cancer–related illness.

•DRE and PSA measurements can have both false-positive and falsenegative results.

•Prostatic biopsy can be uncomfortable and carries a small risk of sepsis or significant bleeding.

•Repeat biopsy may be recommended (PIN, ASAP, or rising PSA).

•Treatment may not be necessary, or may not be curative.

•Aggressive therapy is necessary to realize any benefit from screening if cancer is found based on the screening biopsy.

•Treatment-related morbidity could lead to a reduction in quality of life.

•Active surveillance may be recommended if a low-risk cancer is found.

196 CHAPTER 6 Urological neoplasia

Prostate cancer: clinical presentation

Since the widespread use of serum PSA testing, the majority of patients now have organ-confined disease at presentation. Shown below are the possible presentations, grouped by disease stage.

Localized prostate cancer (T1–2)

•Asymptomatic, detected through screening serum PSA (most common) or incidental digital rectal examination (DRE)

•Lower urinary tract symptoms (LUTS) (probably due to coexisting benign hyperplasia causing bladder outflow obstruction)

•Hematospermia

•Hematuria (probably due to coexisting benign hyperplasia)

•Perineal discomfort (probably due to coexisting prostatitis)

Locally advanced cancer (T3–4)

•Asymptomatic, with screening serum PSA or incidental DRE

•Lower urinary tract symptoms

•Hematospermia

•Hematuria

•Perineal discomfort

•Symptoms of renal failure/anuria due to ureteral obstruction

•Malignant priapism (rare)

•Rectal obstruction (rare)

Metastatic disease (N+, M+)

•Asymptomatic (“occult disease”), with screening serum PSA or incidental DRE

•Swelling of lower limb due to malignant lymphatic obstruction

•Anorexia, weight loss

•Bone pain, pathological fracture

•Neurological symptoms/signs in lower limbs (spinal cord compression)

•Anemia