Clinical prostate cancer最新文献

High-grade prostatic intraepithelial neoplasia (HGPIN) is commonly encountered on prostate needle biopsies and, based on epidemiologic, molecular, and animal models, has proven to be the most significant risk factor for prostate cancer and likely represents the premalignant phase of prostatic adenocarcinoma. This lesion is characterized by cellular proliferations within pre-existing ducts and glands, with nuclear and nucleolar enlargement similar to prostate cancer. However, unlike cancer, HGPIN retains a basal cell layer identifiable by immunohistochemistry with the basal cell–specific antibody cytokeratin 34βE12. The incidence of HGPIN identified in needle biopsies is as high as 25%, increases with age, and coexists with prostate cancer in approximately 85% of cases. There appears to be no causal relationship between HGPIN and serum prostate-specific antigen (total, percent free, or density) or radiographic characteristics on transrectal ultrasound. In a large series, the identification of HGPIN on initial needle biopsy is associated with about a 35% risk of prostate cancer on subsequent biopsies. Thus, the finding of HGPIN on prostate needle biopsy necessitates a second biopsy in a patient eligible for curative treatment. As a precursor lesion, HGPIN is currently a target for chemopreventive strategies, including antiandrogens and nutritional supplementation.

The goal of this investigation is to characterize the clinical significance of the rebound interval (RI) after neoadjuvant short-course hormonal therapy (HT) and external-beam radiation therapy (RT), during which the prostate-specific antigen (PSA) may rise because of hormone withdrawal prior to full RT efficacy. The charts of 257 consecutive patients with localized prostate cancer who received short-course neoadjuvant HT and RT were reviewed. A piecewise-linear log PSA versus time curve was generated for each patient and averaged over the population to facilitate identification of the RI start and end dates. Existing definitions of biochemical failure. American Society for Therapeutic Radiology and Oncology (ASTRO), Vancouver and Houston were applied, as were these same definitions modified to exclude failures during the RI. Sensitivity and specificity were analyzed, using no evidence (by digital rectal examination or radiology) of disease failure as the gold standard. The 5-year biochemical survival with different failure definitions were ASTRO versus ASTRO-modified: 81.6% versus 86.7%; Houston versus Houston-modified: 71.4% versus 76.7%; and Vancouver versus Vancouver-modified: 83.5% versus 85.6%. The sensitivity and specificity comparisons were ASTRO versus ASTRO-modified 58.3% versus 33.3%; 91.4% versus 94.3%, Vancouver versus Vancouver-modified: 50% versus 50%; 92.7% versus 95.5%, Houston versus Houstonmodified: 100% versus 66.7%; 90.6% versus 92.2%. The RI after HT and RT is likely not merely an artifact of hormone withdrawal but is correlated with ultimate clinical outcome. Excluding RI failures can marginally improve specificity but may possibly have an unacceptable risk of lowering sensitivity. Further work is needed to design and validate definitions of failure, which account for the RI.

Prostate cancer is a highly prevalent disease in the Western world. In the United States alone, prostate cancer affects approximately 230,000 men and causes the death of 30,000 American men annually. Several theoretical health care measures may be implemented to decrease the morbidity and mortality of any disease. These measures include prevention, screening, improved curative treatment, and the transformation of an acute lethal disease to a chronic, tolerable one. This summary focuses on the screening aspects of prostate cancer.

Brachytherapy for early prostate cancer can cause long-term urinary, bowel, and sexual dysfunction. Modifying technique may mitigate complications, but definitive outcome assessment requires long-term follow-up. Although radiation dose plausibly mediates all treatment-related toxicity, short-term symptoms may indicate long-term outcomes. We sought an early indication of whether a modified brachytherapy technique successfully decreased toxicity in the anticipated direction by assessing changes in symptoms and symptom distress 3 months after treatment. In a prospective study of clinically localized prostate cancer using a validated, patient-reported questionnaire, we assessed 85 men, whose primary treatment was brachytherapy alone, prior to treatment and 3 months after the procedure. Twenty-two men received standard ultrasound-guided brachytherapy (SB), and 63 men received magnetic resonance imaging–guided brachytherapy (MB), a technique intended to decrease urinary toxicity by reducing urethral irradiation. Patient age and other sociodemographic variables were similar in the 2 groups. The MB group experienced a greater increase in urinary obstruction/irritation symptoms (P = 0.02) and sexual function distress, but not sexual dysfunction (P = 0.22), whereas the SB group reported a smaller increase in bowel symptoms (P = 0.04) and bowel distress (P = 0.02). We found reduced short-term urinary obstruction/irritation and increased bowel problems after MB consistent with the hypothesized effects of the modified technique, although no obvious mechanism explains the decreased sexual function distress in MB patients. Whether these short-term changes predict long-term outcome differences will require much longer follow-up. However, these results suggest that measuring early symptoms may indicate whether an altered brachytherapy treatment technique has intended favorable consequences, potentially accelerating technology assessment.

A number of new predictive modeling techniques have emerged in the past several years. These methods, which have been developed in fields such as artificial intelligence research, engineering, and meteorology, are now being applied to problems in medicine with promising results. This review outlines our recent work with use of selected advanced techniques such as artificial neural networks, genetic algorithms, and propensity scoring to develop useful models for estimating the risk of biochemical recurrence and long-term survival in men with clinically localized prostate cancer. In addition, we include a description of our efforts to develop a comprehensive prostate cancer database that, along with these novel modeling techniques, provides a powerful research tool that allows for the stratification of risk for treatment failure and survival by such factors as age, race, and comorbidities. Clinical and pathologic data from 1400 patients were used to develop the biochemical recurrence model. The area under the receiver operating characteristic curve for this model was 0.83, with a sensitivity of 85% and specificity of 74%. For the survival model, data from 6149 men were used. Our analysis indicated that age, income, and comorbidities had a statistically significant impact on survival. The effect of race did not reach statistical significance in this regard. The C index value for the model was 0.69 for overall survival. We conclude that these methods, along with a comprehensive database, allow for the development of models that provide estimates of treatment failure risk and survival probability that are more meaningful and clinically useful than those previously developed.

All forms of androgen-deprivation therapy, including finasteride, induce distinctive histologic changes in benign and neoplastic prostatic epithelial cells, including cytoplasmic clearing, nuclear and nucleolar shrinkage, and chromatin condensation. Treated cancer has a significantly higher architectural (Gleason) grade, lower nuclear grade, and smaller nucleolar diameter than untreated controls, creating the potential for grading bias. Recognition of these changes may be difficult in needle biopsies and lymph node metastases with treated cancer because of the subtle infiltrative pattern and inconspicuous nucleoli. The effects of finasteride may be less pronounced than other forms of therapy with variable distribution throughout the prostate; further, there may be greater sensitivity of low and intermediate-grade cancer than highgrade cancer. The Gleason grading system for cancer should not be used after finasteride treatment as it is not validated in this setting and is likely to overestimate the biologic potential of high-grade cancer observed after therapy. Chemoprevention trials with agents such as finasteride that alter morphology should not rely on cancer grading as a secondary endpoint owing to grading bias.

As a result of demographic evolution, oncologists will treat more and more elderly patients with prostate cancer. Aging is frequently associated with the coexistence of several medical complications that can increase the complexity of cancer treatment decision-making. Unfortunately, clinical oncologists need to be more familiar with the multidimensional assessment of elderly patients. To acquire this skill, we implemented a multidimensional geriatric assessment program at our cancer center. This instrument prospectively assessed 60 elderly patients with prostate cancer. Herein, we describe geriatric aspects detected in our patient sample and report treatment options proposed to elderly patients with prostate cancer at different disease stages. The minimal comprehensive geriatric assessment (mini-CGA) procedure revealed that 66% of our patient population was dependent in one or more of the Katz Activities of Daily Living and 87% were dependent in 1 or more of the Lawton Instrumental Activities of Daily Living; all patients had significant comorbidity according to the Cumulative Illness Rating Scale–Geriatrics, 75% having at least one severe comorbidity. We identified 19 cases of drug interaction. We also observed that half of these patients had a risk of falling and some physical disability; 45% had cognitive disorders requiring more investigation; one third had depressive symptoms. Finally, 65% of the patients were either malnourished or at risk of malnutrition. Many of these problems were unknown before the mini-CGA processing and may interfere with cancer and cancer treatment. Thus, the correct management of elderly patients with cancer requires comprehensive geriatric assessment as well as relevant disease staging at diagnosis. This approach will help us to propose the most appropriate treatment with the main aim of preserving quality of life.