Detection and treatment of prostate cancer can theoretically identify and cure a potentially disabling and deadly disease. However, controversy exists primarily because of the absence of randomized controlled trials (RCTs) documenting that these strategies improve survival and quality of life. In the absence of definitive information from RCTs, patients seek information and recommendations from many sources. Physicians have an opportunity to help patients and their families sort through the vast array of conflicting and confusing information. Rather then recommending for or against routine prostate-specific antigen (PSA) testing, physicians should provide men who are interested in prostate cancer testing, 50 years of age and older, and have a life expectancy of at least 10 to 15 years, with balanced information about the potential benefits and established harms of screening, diagnosis, and treatment. Validated informational materials can effectively and efficiently promote shared decision making. For early prostate cancer detection, the minimum information should include: the likelihood that prostate cancer will be diagnosed, possibilities of false-positive and false-negative results, anxiety associated with a positive test, and uncertainty regarding whether screening reduces the risk for death from prostate cancer. For men with localized prostate cancer, acceptable treatment options include radical prostatectomy, radiation therapy, cryotherapy, early androgen-suppression therapy, and watchful waiting. These are all considered acceptable options because data do not provide clear-cut evidence for the superiority of any 1 treatment. The only RCT comparing surgery to watchful waiting, though of relatively small size and conducted before PSA testing, showed no difference in survival after 23 years of follow-up. Watchful waiting does not remove prostate cancer, may miss an opportunity to cure or delay disease progression, and may lead to increased patient anxiety. However, watchful waiting avoids the harmful side effects of early intervention and does provide palliative therapy if and when symptomatic disease progression occurs. Furthermore, intervention is not necessary in the vast majority of men because most prostate cancers do not cause mortality or serious morbidity. Therefore, quality of life in many men treated with watchful waiting is superior to those treated with early intervention. For the minority of men with prostate cancer likely to cause disability or death, early intervention options may not be effective. Although commonly used in other countries, watchful waiting is rarely recommended in the United States. The opportunity exists to resolve the confusion, close the gaps in knowledge, and enhance prostate cancer care by conducting RCTs. Until these RCTs are completed, physicians can assist patients by providing a balanced presentation of the known risks and potential but unproven benefits of detection and treatment options and incorporating patient preferences into health care decisions.
Adjunctive surgical resection of residual disease after chemotherapy is a critical part of the comprehensive management of patients with advanced nonseminomatous germ-cell tumor (NSGCT). Surgical resection is indicated in the presence of residual radiographic abnormalities and normal serum tumor markers. Necrosis, teratoma, and viable carcinoma can be found at any resected site. After induction chemotherapy, necrosis comprises approximately 50% of histologic findings, teratoma 40%, and viable GCT the remaining 10%. A number of investigators have attempted to predict the presence of necrosis in an effort to obviate surgery. A number of variables predictive of necrosis have been identified and tested prospectively, including: degree of tumor shrinkage, size of pre- and posttreatment mass(es), prechemotherapy markers, and teratomatous components in the orchiectomy specimen. However, the risk for a false-negative prediction remains approximately 20%. The most rigorous approach remains a retroperitoneal lymph node dissection (RPLND). Furthermore, the histologic discordance between different sites ranges from 29% to 46%; thus, all sites of residual disease should be resected. The patient's prognosis is influenced by: (1) completeness of resection, and (2) biology of the tumor (histology of residual mass(es), marker status at the time of RPLND, and prior burden of therapy). Surgical boundaries and completeness of dissection should not be compromised in an attempt to preserve ejaculation.
Tremendous progress has been made in the treatment of testicular seminoma over the past 25 years. The advent of curative cytotoxic chemotherapy, even for patients with advanced metastatic disease, has led to a paradigm shift toward minimizing additional oncologic therapies and their potential side effects. Despite these advances, controversial issues still exist in managing patients with this disease. Patients with stage I disease can now be managed successfully with close surveillance or postoperative radiotherapy (RT). Although deemed safe, considerable debate persists about surveillance including issues of compliance, cost, and secondary effects of routine RT. Aside from RT, patients with stage I disease also can be managed with one- or 2-dose single-agent carboplatin. Although this appears safe and efficacious, an ongoing randomized study is underway to compare its effectiveness with that of RT. Residual mass after chemotherapy for seminoma is not uncommon and therapeutic options include observation, RT, or retroperitoneal lymphadenectomy. Although most agree that patients with small (<3 cm) or ill-defined masses can be observed, debate persists as to the optimal management of patients with well-defined masses greater than 3 cm. For many years, patients with bulky retroperitoneal disease (>5 cm) were treated with up-front radiotherapy and chemotherapy at relapse. The high failure rate outside the treatment field has now changed this paradigm to one of up-front chemotherapy.
Management options for patients who have stage II nonseminomatous germ cell cancer, completely resected at retroperitoneal lymph node dissection (RPLND), include two cycles of adjuvant cisplatin-based chemotherapy or close surveillance, with chemotherapy reserved for patients who relapse. Both options are associated with cure in an equally high percentage of patients. The choice of options is influenced by the extent of the tumor resected and patient compliance. Surveillance is a strong consideration for patients who have low-volume nodal disease at RPLND because the relapse proportion is 30% or less. In contrast, patients who have high-volume nodal involvement at RPLND have a relapse rate of 50% to 90% with surveillance alone, and adjuvant chemotherapy is the preferable option in this group.
Prostate cancer remains the most commonly diagnosed noncutaneous malignancy in American men. Currently, there are 3 standard treatment options available to men with early prostate cancer: expectant management, radiation therapy, and radical prostatectomy. Although a number of studies have evaluated survival after treatment for early prostate cancer, the optimal choice of therapy for any given patient remains a difficult decision and requires the consideration of a variety of patient and tumor factors. The final selection of therapy for early prostate cancer should be based on an informed discussion between the physician and patient. To accomplish this goal, patients must be made familiar with the pertinent factors that affect survival. We review the factors most relevant for patients to understand as they consider their treatment options for early prostate cancer and summarize the data for physicians who counsel them.
The application of artificial neural networks (ANNs), especially feed-forward neural networks (FFNNs), has become very popular for diagnosis and prognosis in clinical medicine, often accompanied by exaggerated statements of their potential. The excitement stems mainly from the fact that ANNs were developed as attempts to model the decision process of the human brain. Traditionally, logistic regression models and proportional hazard regression models have been used in these applications. In this article, FFNNs are introduced as flexible, nonlinear regression models and necessary precautions for their use are discussed. Furthermore, the results of a literature survey of applications of ANNs in prostate cancer published between 1999 and 2001 are described; most applications suffer from methodologic deficiencies. It is concluded that there is so far no evidence that the application of ANNs provide real progress in the field of diagnosis and prognosis in prostate cancer.
Monoclonal antibodies (mAbs) to prostate-specific antigens, such as PSMA, have great potential as diagnostic and therapeutic tools in the management of advanced prostate cancer. PSMA is a very attractive target for mAb-based imaging. It is expressed by virtually all prostate cancers and its expression is further increased in poorly differentiated, metastatic, and hormone-refractory carcinomas. The ProstaScint scan (Cytogen, Princeton, NJ), based on the mAb 7E11-C5.3, is currently approved for the imaging of prostate cancer in soft tissue but is not approved for imaging bone metastases. It appears superior to conventional imaging studies for soft-tissue disease but has limitations attributed to its intracellular binding site on PSMA. Overcoming this limitation, new mAbs to the extracellular domain of PSMA have been developed. The radioisotopes, (111)Indium, (90)Yttrium, and (177)Lutetium have been conjugated to one such mAb, J591. Radioimmunoscintigraphy with this immunoconjugate has demonstrated excellent tumor targeting of prostate cancer sites not only in soft tissue but also in bone.
Patients with newly diagnosed, clinically localized prostate cancer need information concerning long-term outcomes to make informed decisions regarding treatment options. Several nomograms have been developed that can help in this decision process. By using a nomogram originally published in 1998, patients and clinicians can predict the 15-year clinical outcomes in the absence of aggressive treatment based on age and Gleason score at diagnosis. These predictions are based on patients diagnosed and treated before the routine use of PSA that has accelerated the diagnosis of prostate cancer by at least 5 years. Longer follow-up of contemporary patients will determine whether this nomogram remains accurate in the prostate-specific antigen (PSA) era. In view of the lead-time bias resulting from PSA testing, the outcomes of contemporary patients are likely to be better rather than worse than the results shown.
Many nomograms are currently available for patients' and physicians' use for prediction of pathologic stage based on preoperative parameters, such as prostate-specific antigen (PSA) level, clinical stage (tumor, node, metastasis), and Gleason score from prostate biopsy specimen. Based on the probability of final pathologic stage as well as patient comorbidity and life expectancy, patients and physicians can decide whether definitive local therapy, systemic therapy, or palliative therapy would be most appropriate. Nomograms have also been developed based on preoperative parameters for prediction of biochemical recurrence-free survival outcome following surgery. These nomograms can help patients understand the long-term cancer cure rates after radical prostatectomy.
In the 60 years since Huggins first demonstrated the hormone dependency of prostate cancer, the introduction of various means of hormonal manipulation has resulted in modest achievements. Orchiectomy reduced testosterone but was irreversible and associated with reduced quality of life. Diethylstilbestrol (DES) represented the first alternative to surgical castration. However, cardiovascular adverse events severely limited its use. The luteinizing hormone-releasing hormone (LHRH) agonists offered true medical castration but suffered from problems of testosterone surge and tumor flare. The introduction of antiandrogens in combination with LHRH agonists appears on meta-analysis not to have improved survival and has implications for the cost and convenience of therapy, as well as added toxicity. Gonadotropin-releasing hormone (GnRH) antagonists offer for the first time a truly rapid medical means of reducing testosterone and also suppress follicle-stimulating hormone (FSH). However, the clinical benefit of this new class of drugs remains to be evaluated.
About 5% of all patients with unilateral testis cancer harbor testicular intraepithelial neoplasia (TIN) in their contralateral testicle, which will progress into an invasive germ-cell tumor over time. Accurate diagnosis of TIN by a random surgical testis biopsy examination and effective therapy by local radiation has led to the concept of a contralateral screening biopsy procedure in all testis cancer patients. Screening and preventive treatment, however, only are indicated if (1) therapeutic outcome of the screened population is improved and (2) physiologic function of the affected organ might be maintained. Based on a critical review of the literature, some drawbacks of this policy have to be considered and the routine indication for contralateral testis biopsy procedure has to be questioned: (1) all TIN-negative patients still have to undergo meticulous follow-up evaluation for metachronous testis cancer owing to a false-negative biopsy diagnosis rate of 0.3%; (2) testis biopsy procedure is associated with a 15% to 20% complication rate, which might a negative impact on endocrine and exocrine testicular function; (3) local radiation of TIN results in irreversible infertility owing to eradication of spermatogenesis; (4) local radiation of TIN results in an impairment of endocrine Leydig cell function in 25% of patients; (5) therapeutic outcome and prognosis will not be improved in irradiated patients as compared with patients on surveillance; (6) local tumor resection for the management of metachronous testicular cancer represents an effective and viable option. The current literature does not support the strategy to perform contralateral testis biopsy procedures in all patients with unilateral testicular germ-cell tumors. Testis biopsy procedures might, however, be offered to high-risk (34%) patients for contralateral TIN with a testicular volume less than 12 mL, a history of cryptorchidism, and an age less than 30 years.
Following orchiectomy in patients with stage 1 nonseminomatous germ-cell tumors (NSGCT), there are three treatment options. Retroperitoneal lymph-node dissection (RPLND) is currently the treatment of choice in the United States and can be both diagnostic and therapeutic but is associated with surgical morbidities. Surveillance is the least invasive but carries the highest potential for relapse and can be timely and costly for both patient and physician. Primary chemotherapy avoids the morbidity of surgery while achieving similar survival rates, albeit with potentially significant side effects. The advantages and disadvantages of each treatment modality are discussed.
The increased use of prostate-specific antigen (PSA) in screening for preclinical disease after 1985 is thought to be a major determinant of the changing patterns in prostate cancer incidence; however, the long-term effect of screening on future trends in mortality and survival is uncertain. This article reviews the temporal trends (1981-1998) for prostate cancer incidence, mortality, and survival, and projects prostate cancer incidence and mortality rates for 1999 to 2001. Autoregressive, quadratic, time-series models were used to describe prostate cancer mortality rates in the US population and prostate cancer incidence rates derived from the National Cancer Institute's (NCI) Surveillance, Epidemiology and End Results (SEER) program. These models were based on data collected from 1979 through 1998, with forecasts produced for 1999 to 2001. Prostate cancer incidence increased steadily from 1981 to 1989, with a steep increase in the early 1990s, followed by a decline. Incidence rates were forecasted to remain stable through the year 2001. Mortality rates decreased steadily and were forecasted to continue to decrease concurrently with increasing 5- and 10-year relative survival rates. The incidence, mortality, and survival trends were comparable in US blacks, who exhibited on average 2-fold higher mortality and 50% higher incidence than whites. Decreasing prostate cancer mortality and increasing relative survival trends in the United States were described after the introduction of PSA screening. However, the exaggerated rate of increase in the early 1990s in prostate cancer incidence was transient and likely a result of increased detection of preclinical disease that was prevalent in the general population.
Prostate cancer can be effectively treated with either external beam radiation techniques or with brachytherapy. This study was designed to address the methodology that is used to assess outcome data in the current radiation literature and to evaluate available nomograms that can be used to predict outcomes. A literature search was performed and 12 articles reviewed. Risk stratification was the most frequently used methodology to analyze data. This method encompasses disease-specific variables: the pretreatment prostate-specific antigen (PSA) value and the Gleason score are classified by using cut points into low, intermediate, and high-risk groups. Another methodology uses nomograms to predict outcome. The nomogram uses continuous values of each variable so that the outcome probability for a specific set of parameters is quite specific. The advantage of nomogram analysis over risk stratification analysis is presented. In conclusion, only 3 reports were identified in the radiation literature that used a nomogram to predict outcome. One of the nomograms is proprietary and difficult to interpret. The other 2 nomograms, 1 for 3-dimensional radiation and the other for brachytherapy, have been incorporated into hand-held devices that can be used at consultation with the patient to discuss outcome probabilities to assist in treatment decisions.
As a result of prostate cancer screening programs, approximately 10% of otherwise healthy men will be found to have an elevated prostate-specific antigen (PSA) level and therefore be at risk for harboring prostate cancer. Patients with an elevated PSA level have a wide variation in the risk for having prostate cancer diagnosed by transrectal ultrasound (TRUS)-guided prostate biopsy. To adequately counsel these patients, some form of individualized risk assessment must be given. There are several tables, artificial neural network (ANN) models, and nomograms that are available to stratify an individual patients risk for having prostate cancer diagnosed by a TRUS biopsy, either initially or on subsequent biopsies after a previous negative biopsy. Presently, nomograms are also being developed to predict the risk not only for having prostate cancer but also for clinically significant prostate cancer. The difficulty in calculating this risk for an individual patient is that the multiple competing clinical and pathologic factors have varying degrees of effect on the overall risk. This problem of competing risk factors can be overcome by the use of nomograms or ANNs. This article reviews the available instruments that are available to the urologist to enable prediction of the risk for having prostate cancer diagnosed by TRUS-guided prostate biopsy.
With the introduction of helical CT and its ability to acquire images very rapidly, new problems are being encountered, which can profoundly affect the quality of CT examinations performed for evaluation of known or suspected renal masses. In this article, these problems are summarized and recommendations made for CT techniques that will maximize sensitivity and specificity in renal mass detection, accuracy in renal mass characterization, and accuracy in staging of renal cancer.
Management of carcinoma of the prostate has traditionally been guided by digital rectal examination, and by laboratory data such as serum prostate-specific antigen (PSA) level and histopathologic tumor grade. The introduction of the endorectal coil has improved the ability of magnetic resonance imaging (MRI) to contribute to staging and treatment planning of prostate cancer, especially in cases of confined or locally invasive disease. Exciting research in the fields of magnetic resonance spectroscopy (MRS) and MR-guided intervention of the prostate may soon expand the role of MRI in the diagnosis and treatment of prostate cancer. This article reviews current MRI techniques, the MRI features of prostate cancer, the role and efficacy of MRI in prostate carcinoma staging, and the current and future uses of MR spectroscopy and MR-guided prostate brachytherapy.
The evolution of taxanes as treatment for androgen-independent prostate cancer hes emerged from both the laboratory and clinic. Docetaxel is a potent in vitro inhibitor of Bcl-2, an antiapoptotic gene. Phase I and II studies with docetaxel alone or in combination with estramustine demonstrated promissing median survivals of 14--23 months, higher than what would have been expected for historic controls. Two randomized trials have proven the superiority of docetaxel based treatment in improving survival in men with androgen-independent prostate cancer. SWOG 99-16 and TAX 327 found that docetaxel-based therapy reduced the risk of death by 20--24% when compared to mitoxantrone-based therapy. Future trials will build on docetaxel-based combinations with novel targeted agents.
Prostate cancer is the second leading cause of cancer mortality among men in Western countries. The initial treatment of advanced prostate cancer is suppression of testicular androgen production by medical or surgical castration, but nearly all men with metastases develop disease progression. Patients with hormone-resistant prostate cancer (HRPC) have a median survival of approximately 18 months, and no therapy has yet demonstrated a definitive survival advantage. However, in the past several years, a number of promising new treatment strategies have emerged. One of the most important new treatment strategies involves secondary hormonal manipulation after the failure of primary androgen deprivation. This approach is predicated on the recognition that HRPC is a heterogeneous disease, and some patients may respond to alternative hormonal interventions despite the presence of castrate levels of testosterone.
