Prostate Cancer

Permanent prostate brachytherapy with or without supplemental therapies is a highly effective treatment for clinically localized prostate cancer, with biochemical outcomes and morbidity profiles comparing favorably with competing local modalities. However, the absence of prospective randomized brachytherapy trials evaluating the role of supplemental external-beam radiation therapy (XRT) has precluded the development of evidence-based treatment algorithms for the appropriate inclusion of such treatment. Some groups advocate supplemental XRT for all patients, but the usefulness of this technology remains largely unproven and has been questioned by recent reports of favorable biochemical outcomes following brachytherapy used alone in patients at higher risk. Given that brachytherapy can be used at high intraprostatic doses and can obtain generous periprostatic treatment margins, the use of supplemental XRT may be relegated to patients with a high risk of seminal vesicle and/or pelvic lymph node involvement. Although morbidity following brachytherapy has been acceptable, supplemental XRT has shown an adverse impact on long-term quality of life. The completion of ongoing prospective randomized trials will help define the role of XRT as a supplement to permanent prostate brachytherapy.

Permanent prostate brachytherapy with or without supplemental therapies is a highly effective treatment for clinically localized prostate cancer, with biochemical outcomes and morbidity profiles comparing favorably with competing local modalities. However, the absence of prospective randomized brachytherapy trials evaluating the role of supplemental external-beam radiation therapy (XRT) has precluded the development of evidence-based treatment algorithms for the appropriate inclusion of such treatment. Some groups advocate supplemental XRT for all patients, but the usefulness of this technology remains largely unproven and has been questioned by recent reports of favorable biochemical outcomes following brachytherapy used alone in patients at higher risk. Given that brachytherapy can be used at high intraprostatic doses and can obtain generous periprostatic treatment margins, the use of supplemental XRT may be relegated to patients with a high risk of seminal vesicle and/or pelvic lymph node involvement. Although morbidity following brachytherapy has been acceptable, supplemental XRT has shown an adverse impact on long-term quality of life. The completion of ongoing prospective randomized trials will help define the role of XRT as a supplement to permanent prostate brachytherapy.

A previously unknown virus, a xenotropic murine-like retrovirus or XMRV, has been shown to be 30 times more common in men with prostate cancer who are homozygous for a defect in the HPC1 gene than in men without the mutation

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.