Ten-year follow-up of neoadjuvant therapy with goserelin acetate and flutamide before radical prostatectomy for clinical T3 and T4 prostate cancer: update on Southwest Oncology Group Study 9109.

OBJECTIVE: To update the results with 10-year data of a phase II prospective trial of neoadjuvant hormonal therapy with goserelin acetate and flutamide followed by radical prostatectomy for locally advanced prostate cancer (SWOG 9109). The optimal management for clinical stage T3 and T4 N0,M0 prostate cancer is uncertain. MATERIALS AND METHODS: Sixty-two patients with clinical stage T3 and T4 N0,M0 prostate cancer were enrolled. Cases were classified by stage T3 vs T4 and by volume of disease (bulky >4 cm and nonbulky ≤ 4 cm). RESULTS: Fifty-five of 61 eligible patients completed the trial with radical prostatectomy after neoadjuvant androgen deprivation therapy (ADT). The median preoperative prostate-specific antigen value was 19.8 ng/mL, and 67% of patients had a Gleason score of ≥ 7. Among 41 patients last known to be alive, median follow-up is 10.6 years (range 5.1-12.6). In all, 38 patients have had disease progression (30/55, 55%) or died without progression (8/55, 15%) for a 10-year progression-free survival (PFS) estimate of 40% (95% CI 27-53). Median PFS was 7.5 years, and median survival has not been reached. The 10-year overall survival (OS) estimate is 68% (95% CI 56-80). CONCLUSIONS: In this small, prospective phase II study, neoadjuvant hormonal therapy with goserelin acetate and flutamide followed by radical prostatectomy achieves long-term PFS and OS comparable with alternative treatments. This approach is feasible and may be an alternative to a strategy of combined radiation and ADT.

Health-related quality of life results in pathologic stage C prostate cancer from a Southwest Oncology Group trial comparing radical prostatectomy alone with radical prostatectomy plus radiation therapy.

PURPOSE: To compare short- and long-term effects of adjuvant treatment versus observation after surgery on health-related quality of life (HRQL) of prostate cancer patients. PATIENTS AND METHODS: The Southwest Oncology Group (SWOG) intergroup trial compared radical prostatectomy (RP) plus observation versus RP plus adjuvant radiation therapy (RT). Two-hundred seventeen of 425 therapeutic trial patients were eligible and registered to the HRQL study. Patients completed the SWOG Quality of Life Questionnaire (emotional, physical, social, and role function; general symptom status; treatment/disease-specific symptoms; and global HRQL [GHRQL]) at baseline, 6 weeks, 6 months, and annually for 5 years. Prespecified outcomes were three genitourinary symptoms (bowel function tenderness, frequent urination, and erectile dysfunction [ED]) and measures of physical and emotional function. Adjustments were made for the baseline score. RESULTS: Patients receiving adjuvant RT reported worse bowel function (through approximately 2 years) and worse urinary function. There were no statistically significant differences for ED. GHRQL was initially worse for the RP+RT arm but improved over time and was better at the end of the period than the GHRQL reported for RP alone (treatment arm x time interaction, P = .0004). Symptom distress was significantly worse for the RP+RT arm compared with the RP alone arm, but the treatment arms did not differ with respect to other general measures of HRQL. CONCLUSION: The addition of RT to surgery resulted in more frequent urination, as well as early report of more bowel dysfunction, although bowel function differences disappeared over the 5-year period. The addition of RT did not negatively impact ED.

Erectile function outcome reporting after clinically localized prostate cancer treatment.

PURPOSE: In conjunction with the assignment to update the Guidelines for Management of Clinically Localized Prostate Cancer, the American Urological Association Prostate Cancer Guideline Update Panel performed a side analysis of the reporting of erectile function outcomes in this clinical context as published in the medical literature. MATERIALS AND METHODS: Four National Library of Medicine PubMed(R) Services literature searches targeting articles published from 1991 through early 2004 were done to derive outcome reporting (efficacy or side effects) for the treatment of clinical stage T1 or T2 N0M0 prostate cancer. A database was constructed containing descriptions relating to erectile function as well as numerical frequency rates of complete erectile dysfunction, and partial and intact erectile function for various treatments. A literature review was also done, consisting of a PubMed Services search of current measures and protocols used for assessing erectile function outcomes and a survey of consensus opinion sources on the management of male sexual dysfunctions. RESULTS: Based on inclusion criteria 436 articles were selected. Of these articles database extraction from 100 pertaining to radical prostatectomy garnered various characterizations of erectile function, including qualitative descriptions, generic terminology and rating systems. Database extraction from 31 articles, in which results for at least 50 patients were reported, yielded ranges of rates for complete erectile dysfunction, partial erectile function and intact erectile function that were 26% to 100%, 16% to 48% and 9% to 86% for radical prostatectomy, 8% to 85%, 21% to 47% and 36% to 63% for external beam radiation, and 14% to 61%, 21% and 18% for interstitial radiation, respectively. The literature review showed an evolution in standards for studying and reporting erectile function outcomes. CONCLUSIONS: Clinical studies reporting erectile function outcomes after localized prostate cancer treatment often demonstrate poorly interpretable and inconsistent manners of assessment as well as widely disparate rates of erectile dysfunction and erectile function. Future studies must apply scientifically rigorous methodology and standard outcomes measures to advance this field of study.

Variation in the definition of biochemical recurrence in patients treated for localized prostate cancer: the American Urological Association Prostate Guidelines for Localized Prostate Cancer Update Panel report and recommendations for a standard in the reporting of surgical outcomes.

PURPOSE: The American Urological Association Prostate Guideline Update Panel was charged with updating the Guidelines for Clinically Localized Prostate Cancer. In assessing outcomes with treatment, it became apparent that a highly variable number of definitions exist with respect to biochemical recurrence. Herein, we review the variability in published definitions of biochemical recurrence and make recommendations directed toward improving this terminology by recommending a standard definition in patients treated with radical prostatectomy. MATERIALS AND METHODS: Four PubMed literature searches were performed between May 2001 and April, 2004 and covered articles published from 1991 through early 2004. The search terms included the MeSH major headings of prostate cancer and prostatic neoplasm. All potentially relevant articles were retrieved and a more detailed screen for relevance was performed. An article was considered relevant if it reported treatment outcomes of patients with clinical T1 or T2N0M0 prostate cancer. Data extractors recorded the definition of biochemical recurrence and definitions were then collapsed into categories representing the same criteria. The results of biochemical failure were subcategorized by initial treatment. RESULTS: Of 13,800 citations, a total of 436 articles were selected. Among these, a total of 145 articles contained 53 different definitions of biochemical recurrence for those treated with radical prostatectomy. Of these, the most common definition (35) was a prostate specific antigen of >0.2 ng/mL or a slight variation thereof. In addition, a total of 208 articles reported 99 different definitions of biochemical failure among those treated with radiation therapy. Of these, the American Society for Therapeutic Radiology and Oncology definition (70) and/or a variation thereof was the most commonly reported. In total, 166 different definitions of biochemical failure were identified. Following radical prostatectomy, the Panel recommends defining biochemical recurrence as an initial serum prostate specific antigen of > or =0.2 ng/mL, with a second confirmatory level of prostate specific antigen of >0.2 ng/mL. The Panel recommends the use of the American Society for Therapeutic Radiology and Oncology criteria for patients treated with radiation therapy and acknowledges that these criteria will soon be updated although not yet published. CONCLUSIONS: A high degree of variability in the definition of biochemical recurrence exists following treatment for localized prostate cancer. Strict definitions for biochemical recurrence are necessary to identify men at risk for disease progression and to allow meaningful comparisons among patients treated similarly. The Panel acknowledges the American Society for Therapeutic Radiology and Oncology criteria and future modifications thereof for those receiving radiation therapy and recommends the newly developed American Urological Association criteria for those treated with radical prostatectomy. The purpose for the establishment of this standard is for data reporting purposes and for comparison of similarly treated patients. It is not intended to represent a threshold value for which to initiate treatment. The Panel acknowledges that the clinical decision to initiate treatment will be dependent on multiple factors including patient and physician interaction rather than a specific prostate specific antigen threshold value.

Chemoprevention of prostate cancer.

Prostate cancer is a common malignancy with multiple potential opportunities for cancer prevention. As the genetic basis of this malignancy is further understood, prevention strategies will be developed for individual patients based on specific risk factors and pathways of carcinogenesis. The PCPT has conclusively proven that prostate cancer prevention is possible. The results of the SELECT should be available within several years. An enormous challenge for the medical community will be the development of an efficient strategy to evaluate the substantial number of dietary, behavioral, and pharmacologic prevention opportunities. Ultimately, the goal of prostate can-cer prevention is to (1) identify men who are destined to develop clinically significant prostate cancer, and (2) provide individualized agents to prevent disease development.

Chemoprevention of prostate cancer with finasteride.

Prostate cancer is a significant cause of disease and death, making it an attractive target for chemoprevention. The association between lifetime exposure to dihydrotestosterone and risk of developing prostate cancer suggests that chemoprevention is possible with 5alpha-reductase inhibition. The recently completed Prostate Cancer Prevention Trial indicates that chemoprevention is possible with the 5alpha-reductase inhibitor finasteride. Development of a cost-effective chemoprevention strategy for prostate cancer is evolving, and is expected to have significant positive economic and public health benefits.

Prostate cancer detection strategies.

Prostate cancer is the most common malignancy in men and, as a result, there has been a nationwide emphasis on screening and detection. With the widespread use of the prostate-specific antigen (PSA), prostate cancer screening effectively detects localized prostate cancer. However, recent reports have identified a significant proportion of prostate cancer in men with low PSA levels. Many of these cancers are higher-grade malignancies. Consequently, PSA may function more effectively as a screening tool when applied over a continuum that is associated with degree of risk, rather than a binary measure. Other markers are currently being investigated. Ideally, a marker will identify the malignancy that is a clinical threat, thereby avoiding intervention for indolent disease. Prevention strategies may be employed for higher-risk patients, and these strategies eventually may be tailored to genetic or other risks.

Mechanisms of disease: Prostate cancer--a model for cancer chemoprevention in clinical practice.

Prostate cancer is a significant cause of cancer death, making it an attractive target for chemoprevention. Epidemiologic studies and the Prostate Cancer Prevention Trial indicate that chemoprevention is possible. Strategies for prevention include hormonal manipulation and limiting accumulation of genetic damage with anti-inflammatory agents and/or dietary antioxidants. Development of an effective chemoprevention strategy for prostate cancer is evolving and will likely serve as a model for chemoprevention of other adult malignancies.

Prognostic features in men who died of prostate cancer.

PURPOSE: Since the advent of widespread prostate specific antigen (PSA) based screening in the United States, the risk of over diagnosis as well as delayed diagnosis due to existing PSA thresholds has become a concern. Treatment decision planning is generally linked to prognostic variables, most notably PSA, clinical stage and Gleason grade. We examined these and other prognostic variables in a cohort of men who ultimately died of prostate cancer. MATERIALS AND METHODS: Of 413 men with prostate cancer in a cohort in San Antonio, Texas between 1993 and 2003 who died of disease we identified 211 who died as a direct result of prostate cancer. In these cases we assessed presenting symptoms, PSA history, tumor stage and Gleason score at diagnosis. RESULTS: Of the 211 men 141 (67%) underwent screening for prostate cancer prior to diagnosis. Of 190 men with PSA data at diagnosis available 7 (3.7%) had PSA less than 4.0 ng/ml and 27 (14%) had PSA 4.0 to 10.0 ng/ml. Clinical stage distribution was cT1 in 21.1% of cases, cT2 in 50.7% and cT3 in 26.8%. Of 167 men for whom biopsy Gleason grade was available 16.8%, 16.2%, 24% and 43.1% had Gleason sum 5 or less, 6, 7 and 8 or higher, respectively. CONCLUSIONS: While most men who ultimately die of prostate cancer have poor prognostic features, a substantial number have features associated with a potentially good prognosis, including low PSA and low Gleason grade. Many men who died of prostate cancer had undergone prior screening. These data demonstrate the need for improved markers of prognosis and continued assessment of the efficacy of screening with PSA.

Local and systemic therapy for patients with metastatic prostate cancer: should the primary tumor be treated?

Data from well-designed, prospective clinical trials are lacking to support treatment of primary tumor in men diagnosed with metastatic prostate cancer. However, a growing body of evidence suggests that treatment of the primary tumor may enhance cancer control and survival in some men. This evidence is examined and recommendations are made for identifying patients with metastatic prostate cancer who may benefit from definitive treatment of the prostate tumor.