Recognize the risk factors for PCa, including family history, age, and race.

Discuss the advantages and disadvantages of screening for PCa.

Recommend a high-vegetable diet to decrease risk for PCa.

List food products found to be beneficial in decreasing risk for PCa.

Cite important studies looking at androgen deprivation plus radiation therapy as treatment for PCa.

Screening: Addressing Patient Concerns
Leonard G. Gomella, MD, Bernard W. Goodwin Professor of Prostate Cancer, Chair, Department of Urology, and Associate Director of Clinical Affairs, Jefferson Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA

Introduction: prostate cancer (PCa) different in each patient; leading solid tumor in men; death rate declining; many controversies involved; frequent media message that PCa not important cancer; PCa one of top 10 causes of death in men >45 yr of age; most patients >65 yr of age when diagnosed; overall lifetime probability 1 in 6; ≈2 million men currently living with PCa; 5-yr survival rate for metastatic disease ≈36%

Family history: majority (>80%) of patients have no family history of PCa; 5% to 10% have history; if 2 first-degree relatives have disease, relative risk increases 2 to 5 times; familial PCa present if >5 affected men in family and average age at diagnosis <55 yr

Other PCa risk factors: age—at age 45 yr, risk 1 in 2500; due to screening, more often detected in younger men; race—Pacific Rim countries have lowest incidence, but incidence increases with geographic proximity to Europe; Japanese-Americans, as early or late immigrants or born in United States, have highest incidence; risk not fixed (depends on area settled, age at time of immigration, and whether person born in United States); black men 61% more likely to develop PCa than white men; potential contributory factors include diet and obesity

Genetic testing: expectations of patients based on what media reports, but, at present, no uniformly accepted genetic test for PCa; uPM3 urine test—Food and Drug Administration (FDA)-approved; gene detection

Screening for PCa: incidence of metastatic PCa dramatically decreasing; number of men initially presenting with metastatic PCa decreasing, as are deaths; dramatic increase in number of men diagnosed with organ-confined disease; 25 yr ago, 5-yr survival ≈70%; presently, 5-yr survival approaching 98% to 99%; slightly >30% for metastatic PCa; most of PCa discovered when still localized (potentially curable); many data sets show that decrease in mortality based on screening; probable effect of screening only widely accepted explanation for decrease in mortality; prospective randomized trial—data from Tyrol, Austria indicate that screening dramatically reduced mortality from PCa, compared to rest of Austria; cost-effectiveness—$8000 to $145000 per quality-adjusted life- year gained; lower than for breast cancer screening

Side effects: urinary function after radical prostatectomy fine in 80% of patients; studies show early PCa treatment beneficial; study showed statistically significant improvement in all parameters (overall mortality and metastasis) with treatment vs watchful waiting

Incidence: man diagnosed with high-grade PCa at 60 to 65 yr of age has high likelihood of dying of PCa; should continue to screen older men for high-risk PCa; more Gleason pattern 4 cancer seen, higher the likelihood of failure of local treatment; study suggests survival advantage in men 65 to 80 yr of age with low- and intermediate-risk PCa undergoing active treatment

Screening: American College of Preventive Medicine does not advise screening for PCa; United States Preventive Services Task Force states that men 75 yr of age, or men who will probably live 10 yr, should not be screened; should offer screening and advice to patients; should not put all men into same category based on guidelines; screening outcomes— if 100 men >50 yr of age take prostate-specific antigen (PSA) test, 85 will have normal PSA and 15 will have higher- than-normal PSA; after further testing, 12 will have no PCa and 3 will have PCa; advantages—PCa significant health problem; organ-confined disease curable; without screening, majority of tumors clinically and pathologically advanced; decline in death rate seen; blood and rectal screening tests widely available and easy; disadvantages—many men die with, rather than of, disease; identification of clinically insignificant cancers; screening expensive (in human and economic terms); limited trials of screening; definitive evidence that decrease in deaths from PCa due to early detection and treatment based on PSA (overwhelming data)

Diet-based Interventions in Active Surveillance Patients
J. Kellogg Parsons, MD, MHS, Assistant Professor of Surgery/Urology and Staff Investigator, Moores Cancer Center, University of California, San Diego, School of Medicine

Introduction: diet for PCa traditionally pushed to field of complementary and alternative medicine; general perception that altering diet in patients with PCa or in healthy men without PCa may slow initiation or progression of disease (based on preclinical [laboratory] and epidemiologic evidence); preclinical evidence focuses on ways in which components of certain nutrients in diet can alter way that PCa cells grow; examples of nutrients include isothiocyanates in cruciferous vegetables, carotenoids, and lycopene; induce apoptosis of PCa cells, inhibit carcinogenesis, promote expression of cytoprotective enzymes that can repair DNA damage, and protect against primary oxidative DNA damage

Plant-based diets: large body of epidemiologic evidence shows that high-vegetable diets decrease risk for PCa and possibly decrease progression once patient diagnosed; 2 major types of vegetables; cruciferous vegetables—eg, broccoli, brussels sprouts, cauliflower; induce expression of cytoprotective enzymes in prostate that possibly inhibit carcinogenesis; tomatoes and lycopene—includes tomato-based products; limit DNA oxidative damage; data suggest that 7 servings of vegetables daily beneficial

Supplements: large epidemiologic studies have found that selenium and vitamin E decrease risk for PCa; Selenium and Vitamin E Cancer Prevention Trial (SELECT)—ongoing; 35000 men enrolled; randomized to selenium, vitamin E, both, or placebo; final results expected in 2013; vitamin E—antioxidant, anti-inflammatory, and protects against DNA damage; recommended dose 400 IU daily; possible cardiovascular (CV) side effects, particularly stroke; dose >400 IU daily not safe; selenium—inhibits cancer growth and induces apoptosis; late data show it also affects androgen receptor; recommended form L-selenomethionine and dose of 200 µg once daily; risk for side effects minimal

Soy products: decrease PCa in large epidemiologic studies; contain phytoestrogens (antioxidants, inhibit tumor cell proliferation, and have estrogenic effects); observational and preclinical evidence not quite as strong as with micronutrients and plant-based diets

Fish: contain omega-3 fatty acids (active ingredient); found to decrease PCa risk in large epidemiologic studies; omega-3 fatty acids alter cyclooxygenase pathways involved in inflammation, inhibit tumor growth, and induce apoptosis; safe to eat 2 to 3 servings of fish weekly; effects not seen with farmed fish (fed cornmeal)

Meat and animal products: increase risk for PCa in large epidemiologic studies; red meat—contains 2-amino-1-methyl-6-phenylimidazo-[4,5]pyridine (PhIP; potent mutagen); risk possibly higher with processed meats; dairy products—increased risk possibly associated with vitamin D (possible inverse association with risk for PCa); dietary fat—association between obesity and PCa; increases risk for aggressive cancer; suggested that weight loss associated with 40% reduction in risk for high-grade cancer; pomegranate juice—in single clinical trial, found to increase PSA doubling time in patients with biochemical recurrence; limited laboratory studies and no epidemiologic studies; possibly has proapoptotic, antiproliferative, and antioxidant properties in vitro

Selected studies: University of Washington—biopsied participants diagnosed with PCa put on low-fat and low-glycemic diet for 6 wk, then underwent surgery; found significant changes in gene expression profile after change in diet; University of California, San Francisco—93 participants randomized to vegetable-intense diet and lifestyle changes instituted; found that intervention group had significantly decreased PSA levels and progression of treatment; study—10 participants with biochemical recurrence after surgery or radiation therapy; also placed on vegetable-intense diet and lifestyle changes; found increased PSA doubling time; Men’s Eating and Living (MEAL) study—adapted from study on breast cancer; combined with telephone-based dietary counseling; participants counseled to have vegetable-intense diet; each participant assigned to counselor; counselor builds “self-efficacy”; goal 7 servings of vegetables daily; controls given dietary recommendations on paper; found significant vegetable intake and significant difference in fat intake between 2 groups; also found significant change in plasma carotenoid levels pre- and postintervention; next step to determine whether dietary changes decrease progression in active surveillance patients; advise patients to eat fresh foods, mostly plants

High-risk Cancer: Combination Androgen Deprivation and Radiation Therapy
Allan Pollack, MD, Senior Member, and Gerald E. Hankz Endowed Chair in Radiation Oncology, Fox Chase Cancer Center, Philadelphia

Role of androgen deprivation (AD): speaker looked at class 1 evidence of external beam radiation therapy (EBRT) and AD; available series divided into short-term (STAD; 6 mo), intermediate (ITAD; >6 mo to <2 yr), and long-term (LTAD; ≥ 2 yr); studies show survival benefit with STAD and RT; also seen with LTAD and standard doses of radiation; all series used standard doses of radiation; unable to show survival advantage with higher doses of RT alone, but seen with addition of hormone therapy

Radiation Therapy Oncology Group (RTOG) 86-10: patients given 2 mo of AD before RT, then AD continued during RT; benefit seen for all end points, except survival; with 4 mo of AD, effects include decrease in distant metastasis, biochemical failure, and mortality from PCa

Studies: study—from Trans-Tasman group; published in The Lancet Oncology; compared 3 mo vs 6 mo of AD with RT; AD started 2 mo before RT in 3-mo group and 5 mo before in 6-mo group and compared to RT alone; 3- and 6-mo group performed better than RT-only group, but distant metastasis in 6-mo group better; biggest impact at 6 mo, but difference between 3 mo and 6 mo not statistically significant; those with high-risk disease seemed to benefit most; 2 series found no biochemically significant difference between STAD and ITAD (5 mo vs 10 mo); study—looked at STAD vs RT alone in intermediate- and high-risk patients; standard RT doses; STAD given 2 mo before, during, and after RT; 206 participants; difference in cause-specific mortality seen; few failures (6 participants died) vs none in arm receiving STAD with RT; study—looked at men with rising PSA after EBRT; in those treated with STAD, longer doubling time seen, suggesting that when patients failing after STAD, they may progress at slower rate; results need to be reproduced; similar phenomenon seen in animal model; European Organization for Research and Treatment of Cancer (EORTC) trial—3 yr of LTAD with RT better than RT alone; RTOG 92-02—used 4-mo AD regimen (same as that used in RTOG 86-10); AD given 2 mo before and 2 mo during RT, compared to adding extra 24 mo of AD for total of 28 mo, with standard doses of RT in high-risk disease and locally advanced patients; median follow-up 48 mo; data holding up; only disturbing part of data lack of proof of survival advantage, except in subgroup with Gleason score of 8 to 10; however, gain seen in freedom from death due to PCa, favoring LTAD; question about influence of diabetes, CV events, and CV mortality; update showed no increase in CV mortality between STAD and LTAD; D’Amico trial—6 mo of AD with RT vs RT alone; for all-cause mortality, in men with minimal or no comorbidities, survival benefit pronounced in those treated with combination of RT and AD; in those with significant comorbidities, adding AD possibly detrimental (not statistically significant); update by Roach on RTOG 86-10 showed no increase in CV mortality

STAD vs LTAD: study by Bolla—had same findings as RTOG 92-02; noninferiority study; tried to show lack of difference between STAD and LTAD, but early results indicate difference present; suggests that necessary to treat patients with high-risk disease with LTAD for 2 yr (data suggest 2.5 to 3 yr); in intermediate- and high-risk patients, survival benefit seen with addition of STAD; in high-risk patients, survival benefit greater with LTAD; if using STAD in high-risk patient, unknown whether 6 mo better than 3 mo as suggested by Trans-Tasman trial

Treatment of pelvic lymph nodes: from radiation oncologist’s viewpoint, treating nodal drainage areas in multiple sites beneficial, but difficult to show in PCa; RTOG 94-13—structured to compare timing of STAD (2 mo before and 2 mo during RT) vs starting AD at end of RT; also questioned treating pelvic lymph nodes vs prostate only; initially found that treating whole pelvis beneficial; when all 4 treatment groups looked at, group that received neoadjuvant and concurrent AD and whole-pelvis treatment performed best in freedom from biochemical failure; with recent update by Lawton, data “disintegrated”; purported mechanism when AD timed before and concurrent with RT, had greater effect on pelvic lymph nodes than if AD timed adjuvantly; hypothesis contrasts with D’Amico’s paper, which showed that unnecessary to treat lymph nodes, but still obtain beneficial effect by adding STAD to RT; Lawton’s follow-up study no longer showed any difference between whole pelvis vs prostate only and no difference between neoadjuvant concurrent vs adjuvant AD; results do not corroborate that interaction of STAD beneficial when timed with neoadjuvant therapy given with whole- pelvis irradiation; French study—looked at treatment of whole pelvis vs prostate only; subset of patients received STAD; majority of patients had favorable risk; study power low; in high-risk patients, no benefit from addition of whole pelvis treatment; lack of data to support treating pelvic lymph nodes; although debatable, speaker still treats pelvic lymph nodes, but not as aggressively; dose to prostate more important; in retrospective study, dose to prostate important factor; no data on whether higher doses of RT with AD beneficial (requires clinical trial); high-risk patients routinely treated with higher doses of RT with LTAD