Prostate Cancer

The National Cancer Institute (NCI) has begun the largest, most comprehensive effort to identify genetic risk factors for two major cancers, a 3-year initiative aimed at deciphering which genetic alterations put people at increased risk of developing breast and prostate cancer.

Men with prostate cancer generally make treatment decisions based on differences in the information they receive rather than their own preferences, according to a new review.

Socioeconomic factors predominantly explain racial and ethnic disparities in prostate cancer outcomes, according to a new study.

There are many characteristics that set the military apart from the general population. But there was one particularly appealing characteristic: It is an equal-access-to-care culture. Of course, in a country as large and diverse as America, we can't expect to replicate the equal-access model of the US military. But we can try.

Evidence-based medicine is the key factor in gaining health plan approval of medical interventions. However, this is not the only option.

DENVER-Dose escalation of high dose rate (HDR) brachytherapy may improve long-term survival in men with intermediate- or high-risk prostate cancer, according to findings of a study presented at the 47th Annual Meeting of the American Society for Therapeutic Radiology and Oncology (abstract 63).

DENVER, Colorado-In patients who undergo prostatectomy for stage T3 prostate cancer, adjuvant radiation therapy improves biochemical and clinical disease-free survival and eliminates or delays the need for salvage hormonal therapy, according to a phase III randomized trial presented at the 47th Annual Meeting of the American Society for Therapeutic Radiology and Oncology (abstract 1).

SAN ANTONIO - In patients with clinically advanced (cT3) prostate cancer, radical prostatectomy supplemented with other treatment modalities provides outcomes approaching those typically seen in patients with cT2 prostate cancere

SAN ANTONIO-Some prostate cancer patients may not require salvage radiation therapy (RT) following postprostatectomy PSA failure if they exhibited a low preoperative PSA velocity and have a persistent, nearly stable postoperative PSA level. Anthony V. D’Amico, MD, PhD, presented the findings at the 100th Annual Meeting of the American Urological Association (abstract 1678). Although PSA failure following radical prostatectomy can present a significant risk to the patient, certain PSA failures may not indicate a life-threatening situation. In these cases, subjecting patients to the toxicity associated with radiation therapy may be unnecessary. Dr. D’Amico, of the Dana-Farber Cancer Institute and Brigham and Women’s Hospital, Boston, and his colleagues investigated whether these patients with benign PSA failure could be identified based on diagnostic factors.

ASCO - The selective estrogen-receptor modulator (SERM) toremifene (Acapodene), used to treat advanced breast cancer, halved the risk of prostate cancer at 1 year in men with high-grade prostatic intraepithelial neoplasia (PIN), a randomized, double-blind, placebo-controlled multicenter study has found. Toremifene also was safe and well tolerated, investigators reported. The findings are significant in that 30% to 40% of men with PIN are diagnosed with prostate cancer within 1 year, but treatment for PIN is not available; it is simply monitored until it progresses to cancer, said lead investigator David Price, MD. "This is the first time a drug has shown promise for lowering the incidence of prostate cancer in men with PIN," he said.

Overweight and obesity increase the risk of developing several cancers.Once cancer develops, individuals may be at increased risk of recurrenceand poorer survival if they are overweight or obese. A statisticallysignificant association between overweight or obesity and breast cancerrecurrence or survival has been observed in the majority of populationbasedcase series; however, adiposity has been shown to have less of aneffect on prognosis in the clinical trial setting. Weight gain after breastcancer diagnosis may also be associated with decreased prognosis. Newevidence suggests that overweight/obesity vs normal weight may increasethe risk of poor prognosis among resected colon cancer patients and therisk of chemical recurrence in prostate cancer patients. Furthermore, obesecancer patients are at increased risk for developing problems followingsurgery, including wound complication, lymphedema, second cancers,and the chronic diseases affecting obese individuals without cancer suchas cardiovascular disease and diabetes. Mechanisms proposed to explainthe association between obesity and reduced prognosis include adiposetissue-induced increased concentrations of estrogens and testosterone,insulin, bioavailable insulin-like growth factors, leptin, and cytokines.Additional proposed mechanisms include reduced immune functioning,chemotherapy dosing, and differences in diet and physical activityin obese and nonobese patients. There have been no randomized clinicaltrials testing the effect of weight loss on recurrence or survival inoverweight or obese cancer patients, however. In the absence of clinicaltrial data, normal weight, overweight, and obese patients should beadvised to avoid weight gain through the cancer treatment process. Inaddition, weight loss is probably safe, and perhaps helpful, for overweightand obese cancer survivors who are otherwise healthy.

ORLANDO-A new nomogram may help physicians predict the probability of prostate cancer metastasis in patients with a biochemical recurrence after radical prostatectomy, nomogram codeveloper Zohar A. Dotan, MD, PhD, reported at the

ORLANDO-Being overweight or obese appears to adversely affect a man’s risk of dying from prostate cancer, according to a poster presentation at the 2005 Multidisciplinary Prostate Cancer Symposium (abstract 6). "Men who were overweight

Androgen-deprivation therapy, usually with combined androgenblockade, is standard initial treatment for advanced prostate cancer.With failure of initial treatment, as indicated by rising prostate-specificantigen (PSA) levels, second-line hormonal therapy is usually instituted.Over the past several years, it has become increasingly clear thatsystemic chemotherapy has an important role in hormone-refractorydisease. Phase II trials have demonstrated high PSA and measurabledisease response rates with taxane single-agent and combination treatments.One recent phase III trial showed that docetaxel (Taxotere)/estramustine (Emcyt) significantly improved overall survival, progression-free survival, and PSA response rate compared with mitoxantrone(Novantrone) plus prednisone. Another phase III trial demonstratedthat docetaxel given every 3 weeks plus prednisone significantly improvedoverall survival, PSA response rate, pain relief response rate,and quality of life compared with mitoxantrone and prednisone. Onthe basis of these findings, every-3-week docetaxel plus prednisone isnow considered standard first-line therapy for metastatic hormonerefractorydisease. There is considerable optimism that treatment canbe further improved. Studies of taxane combinations with bevacizumab(Avastin), thalidomide (Thalomid), bortezomib (Velcade), antisenseBcl-2 oligonucleotide, mTOR inhibitors, epidermal growth factor receptorinhibitors, and KDR inhibitors are under way. Randomized phaseIII trials in progress or planned are examining docetaxel in combinationwith imatinib mesylate (Gleevec) or calcitriol and docetaxel/prednisonein combination with bevacizumab and an antisense clusterincompound. Other promising systemic agents include epothilones andatrasentan, and promising vaccines include Provenge, GVAX, andProstvac.

Recent advances in treatment modalities for breast and prostate cancerhave resulted in an increasing number of patients that are cured orthat, despite residual disease, live long enough to start experiencingcomplications from cancer treatment. Osteoporosis is one such problemthat has been increasingly identified in cancer patients. Hypogonadismand glucocorticoid use are the two major causes of bone loss inthese patients. Osteoporosis is characterized by low bone mass and abnormalbone microarchitecture, which results in an increased risk offractures. Vertebral body and hip fractures commonly result in a drasticchange of quality of life as they can result in disabling chronic pain,loss of mobility, and loss of independence in performing routine dailyactivities, as well as in increased mortality. In patients with prostatecarcinoma, androgen-deprivation therapy by either treatment with agonadotropin-releasing hormone (GnRH) or bilateral orchiectomy resultsin increased bone turnover, significant bone loss, and increasedrisk of fractures. Patients with breast cancer are at increased risk forestrogen deficiency due to age-related menopause, ovarian failure fromsystemic chemotherapy, or from the use of drugs such as aromataseinhibitors and GnRH analogs. Several studies have indicated that theprevalence of fractures is higher in breast and prostate cancer patientscompared to the general population. Therefore, patients at risk for boneloss should have an assessment of their bone mineral density so thatprevention or therapeutic interventions are instituted at an early enoughstage to prevent fractures. This article will address the characteristicsof bone loss observed in breast and prostate cancer patients and potentialtreatments.

Granulocyte-macrophage colony-stimulating factor (GM-CSF,sargramostim [Leukine]) is a powerful cytokine that is able to stimulatethe generation of dendritic cells. Adjuvant treatment with continuous lowdoseGM-CSF has been shown to prolong survival of stage III/IV melanomapatients. Data on continuous low-dose GM-CSF therapy in tumorsother than prostate cancer are still lacking.

ORLANDO-A novel therapeutic vaccine therapy (see illustration) increased survival in patients with advanced prostate cancer during a phase III clinical trial, lead investigator Eric J. Small, MD, reported in an oral presentation and a media briefing at the 2005 Multidisciplinary Prostate Cancer Symposium (abstract 264). "This immunotherapy has the potential to provide a new treatment option for a group of patients with precious few options," said Dr. Small, professor of medicine and urology, University of California, San Francisco, School of Medicine. "On a broader scale, this is the first study ever to show a survival advantage for the immune approach in prostate cancer."

ORLANDO-Higher baseline PSA and rapid PSA doubling time (PSADT) are adversely associated with bone metastasis and death in patients with castrate nonmetastatic prostate cancer, according to a study presented at the 2005

Lung cancer is the most commoncause of cancer-relatedmortality in the United Statesand worldwide.[1] In the UnitedStates, lung cancer was responsiblefor an estimated 160,440 deaths in2004. This surpassed the combinedmortality resulting from colorectal,breast, and prostate cancer.

This special supplement to Oncology News International comprises expertcommentary and selected reports from the 2004 meetings of RSNA andASTRO about new imaging techniques, with a focus on state-of-the-art magneticresonance imaging, positron emission tomography, computed tomography,and complementary modalities for improving the diagnosis, staging, andtreatment of a variety of cancers. Evident in these reports is the increasingcollaboration between the specialties of radiation oncology and diagnosticradiology as imaging technology continues to evolve.

The use of hormonal therapy with external-beam radiation (EBRT)to treat prostate cancer is a topic that has been well explored. The potentialuse of hormonal therapy and brachytherapy in the treatment ofprostate cancer, however, continues to be controversial. This review isbased on our current interpretation of the available literature assessingthe outcomes of patients treated with EBRT and brachytherapy withor without hormonal therapy. Extrapolating from the findings of theRadiation Therapy Oncology Group (RTOG) 9413 trial, there appearsto be a favorable interaction between hormonal therapy and irradiationin the lymph nodes. The benefits demonstrated with whole-pelvicEBRT and hormonal therapy are likely to extend to patients treatedwith brachytherapy as well. Studies suggest that the role of hormonaltherapy in brachytherapy is limited without the application of wholepelvicEBRT due to the inability of brachytherapy to address potentiallymph nodes at risk. The potential role of hormonal therapy in conjunctionwith brachytherapy without pelvic radiotherapy, is limited byinconclusive data and abbreviated follow-up times.

Drs. Andrews and Roach present an excellent review and discussion of the existing literature regarding the role of androgen ablation therapy in patients being treated with external-beam radiation therapy (EBRT) and prostate brachytherapy. However, the indications for, and optimal timing of androgen ablation with radiation therapy remain controversial, particularly in regard to brachytherapy.

Several key areas must be considered in the diagnosis and managementof spinal cord compression. Because the outcome can be devastating,a diagnosis must be made early and treatment initiated promptly.Although any malignancy can metastasize to the spine, clinicians shouldbe aware that this occurs more commonly in certain diseases, ie, lungcancer, breast cancer, prostate cancer, and myeloma. The current algorithmfor early diagnosis of spinal cord compression involves neurologicassessment and magnetic resonance imaging of the entire spine.Treatment generally consists of intravenous dexamethasone followedby oral dosing. Depending on the extent of the metastases, symptomsmay also be managed with nonnarcotic pain medicines, anti-inflammatorymedications, and/or bisphosphonates, with local radiation administeredas needed. Surgery has often led to destabilization of the spine.

Icommend the authors for their excellent review and discussion regarding the integration of hormonal therapy with permanent prostate implants. They address several important issues relating to the sequence and duration of hormonal therapy in combination with externalbeam radiation therapy (EBRT) and its underlying relationships with permanent prostate implants.

NEW ORLEANS-A new analysis of long-term zoledronic acid (Zometa) therapy in advanced prostate cancer patients with bone metastases showed significant ongoing benefit, Fred Saad, MD, reported at the 40th Annual Meeting of the American Society of Clinical Oncology (abstract 4575). A second analysis of the data showed that bisphosphonate therapy offers clinical benefit in these patients regardless of whether they had a skeletal-related event (SRE) prior to entry into the study (abstract 4576).

ATLANTA-With the use of highly conformal radiation therapy (RT), men can safely receive a high dose of radiation for early-stage prostate cancer, Anthony L. Zietman, MD, reported at the 46th Annual Meeting of the American Society for Therapeutic Radiology and Oncology (ASTRO abstract 4). Compared with a conventional radiation dose, the high dose was associated with a lower rate of treatment failure.

In their article, Drs. Matthew Cooperberg,Sangtae Park, and PeterCarroll summarize four nationalregistries that have studied risk migration,practice patterns, outcomepredictions, and quality-of-life outcomesin prostate cancer. Each of thesefour large registries-the Prostate CancerOutcomes Study (PCOS), the Departmentof Defense Center for ProstateDisease Research (CPDR), the Cancerof the Prostate Strategic Urologic ResearchEndeavor (CaPSURE), and theShared Equal Access Regional CancerHospital (SEARCH)-has a particularstrength that complements theothers. As more patients enroll in theseregistries, researchers will gain greaterinsight into the patterns of care andclinical and health-related quality oflife for diverse cohorts of prostate cancerpatients.

There are two problems with thepaper by Quaranta et al, neitherof which can be overcomewith discussion or sophistry. The firstconcerns the criteria used to determinewhether a report would be includedin this analysis. Specifically,any series with a median follow-up ofonly 3 years was included if it alsomet the other inclusion criteria. Thisis simply inadequate, as there is greatconsensus that studies with 3-year follow-up miss many recurrences. Thesecond problem with the paper is thedefinition of recurrence. The AmericanSociety for Therapeutic Radiologyand Oncology (ASTRO) criteriaused by the authors has proven inferiorto using a cutoff of 0.2 ng/mL forprostate-specific antigen (PSA) nadirfollowing brachytherapy. The inaccuracyin using ASTRO criteria fordetermining cure by brachytherapy isparticularly pronounced in series withshort follow-up such as the 3-yearmedian follow-up criterion used inthis paper.

Radical prostatectomy and ultrasound-guided transperinealbrachytherapy are both acceptedtreatment options for men with clinicallylocalized prostate cancer.Investigators continue to argue overthe relative effectiveness of each ofthese procedures, not only from thestandpoint of cure, but also with regardto how each treatment affectsquality of life. With the recent closureof a prospective, randomized trial addressingthese issues (the SurgicalProstatectomy Interstitial RadiationIntervention Trial, or SPIRIT) due tolack of patient accrual, it is unlikelythat a direct comparison of these techniqueswill be performed in the foreseeablefuture.

I am honored and delighted to beable to comment on the outstandingcontribution from Drs. Cooperberg,Park, and Carroll relating recentprostate cancer research fromthe various national efforts in prostatedisease research database efforts.As a former director of the Departmentof Defense Center for ProstateDisease Research (DoD-CPDR), Iwas blessed to be able to lead one ofthese database efforts as well as collaboratewith Dr. Carroll and his colleaguesfrom the Cancer of theProstate Strategic Urologic ResearchEndeavor (CaPSURE). Dr. AnthonyD'Amico and his colleagues headedseveral of our joint collaborationsfrom Harvard. In this light, I wouldlike to focus my editorial commentson providing a more in-depth reviewof work[1] that was briefly mentionedin the article by Cooperberg et al.