Predicting clinical end points: treatment nomograms in prostate cancer

Due to the generally indolent nature of prostate cancer, patients must decide among a wide range of treatments, which will significantly affect both quality of life and survival. Thus, there is a need for instruments to aid patients and their physicians in decision analysis. Nomograms are instruments that predict outcomes for the individual patient. Using algorithms that incorporate multiple variables, nomograms calculate the predicted probability that a patient will reach a clinical end point of interest. Nomograms tend to outperform both expert clinicians and predictive instruments based on risk grouping. We outline principles for nomogram construction, including considerations for choice of clinical end points and appropriate predictive variables, and methods for model validation. Currently, nomograms are available to predict progression-free probability after several primary treatments for localized prostate cancer. There is need for additional models that predict other clinical end points, especially survival adjusted for quality of life.     

Hypofractionation for prostate cancer: a critical review

In ideal circumstances, the fractionation schedule of radiotherapy should match the fractionation sensitivity of the tumor relative to the nearby normal tissues. A number of recent publications have suggested that the alpha-beta ratio (alpha/beta) for prostate is low, in the range of 1 to 3 Gy. If alpha/beta is truly low, then hypofractionated schedules using fewer, larger fractions should improve the therapeutic ratio. This critical review examines the clinical experience with hypofractionation. Several prospective trials indicate that toxicity is limited with sophisticated dose delivery and compact clinical target volume to planning target volume margins, but the single-arm nature of these trials precludes definitive statements on efficacy. Several large randomized trials comparing conventional fractionation to hypofractionation are ongoing and are described. Until these trials are completed and the results submitted for rigorous peer review, the notion that alpha/beta for prostate cancer is low remains an unconfirmed hypothesis.     

Comparisons of nomograms and urologists' predictions in prostate cancer

When applying nomograms to a clinical setting it is essential to know how their predictions compare with clinicians'. Comparisons exist outside of the prostate cancer literature. We reviewed these comparisons and conducted 2 experiments comparing predictions of clinicians with prostate cancer nomograms. By using Medline, we searched studies from January 1966 to July 1999 that compared human predictions with nomogram predictions. Next, we conducted 2 experiments: (1) 17 urologists were presented with 10 case vignettes and asked to predict the 5-year recurrence-free probabilities for each patient; (2) case presentations of 63 prostate cancer patients (including full clinical histories with complete diagnostic data and surgical findings) were made to a group of 25 clinicians who were asked to predict organ-confined disease. We found 22 published studies comparing human experts with nomograms, greater than half (13 of 22) showed the nomogram performing above the level of the human expert. Our first experiment showed urologist modification of 165 nomogram predictions led to a decrease in prediction accuracy (c-index decreased from.67 to.55, P <.05). In our second experiment, clinician predictions of organ-confined disease were comparable to the nomogram (area under the receiver operating characteristic curve [AUC] 0.78 and 0.79, respectively). A mixed-model suggests the nomogram did not augment clinician prediction accuracy (doctor excess error 1.4%, P =.75, 95% confidence interval [CI]: -10.9% to 8.2%). Our data suggest that nomograms do not seem to diminish predictive accuracy and they may be of significant benefit in certain clinical decision making settings.     

Clinical utility of microarray-derived genetic signatures in predicting outcomes in prostate cancer

Prostate cancer is a complex heterogeneous disease, and risk stratification remains a significant clinical challenge. Gene microarray has been developed to provide better prediction of clinical outcomes and potentially improve management of patients with various malignancies, including prostate cancer. Currently, several studies are evaluating the clinical significance of gene expression signatures in prostate cancer. These approaches might provide outcome predictions, such as treatment response, progression-free survival, overall survival, and metastatic status and offer new strategies to identify patients at high risk for personalized cancer therapies. This article discusses the latest developments in gene expression-based signatures that predict clinical behavior of prostate cancer. Gene profiling could lead to enhanced early detection and prognosis of prostate cancer, resulting in improved overall survival. The ability to predictclinical outcomes by the microarrayderived genetic signatures is promising; however, further studies are warranted to optimize its clinical utility in patients with prostate cancer.     

Psychosocial interventions to support partners of men with prostate cancer: a systematic and critical review of the literature

Purpose

Prostate cancer poses many challenges for both the man and his partner. Partners have reported a range of issues that impact their own mental health following their partner’s diagnosis of prostate cancer. The aim of this review is to summarise and critically evaluate the current literature reporting psychosocial intervention studies for partners of prostate cancer patients.

Methods

An extensive literature search of electronic databases was conducted (OvidMEDLINE 1946, 26th September 2013, and psychINFO 1967, 26th September 2013) using the keywords prostate cancer AND intervention* OR therapy* OR psychosocial intervention* OR support* AND couple* or Spouse* or Partner* or Intimate partner* matched to the title as well as secondary scanning of reference lists. Studies were included if they described interventions for partners of prostate cancer patients, either solely for the partners or as a couple, intended to alleviate distress and enhance the partner’s or couple’s quality of life, and reported a measurable outcome for partners.

Results

A total of 11 prostate cancer-specific intervention studies that included partners and reported separate results for the partners were found. Only one of these interventions was partner specific, the other eight involved the patient-partner dyad. The studies identified primarily focussed on two areas: emotional distress and sexual intimacy, and mixed findings were reported for efficacy of interventions.

Conclusions

Despite strong evidence that partners of men with prostate cancer experience difficulties associated with the impact of prostate cancer, there is limited research that has investigated the efficacy of psychosocial interventions for partners. Of the reviewed studies, it is evident that interventions targeting the reduction of emotional distress, improved communication and sexual intimacy between the couple and utilisation of strategies that enable partners to express their distress, learn new strategies and implement behavioural change show the most promising results in enhancing partner well-being.

Implications for Cancer Survivors

Significant progress is required in developing and evaluating appropriate and effective psychosocial support interventions for partners of prostate cancer survivors as partners appear to have significant unmet needs in this area.     

Brain metastasis from prostate cancer. Report of 13 cases and critical analysis of the literature

Brain metastasis from prostate carcinoma occurs very rarely. We describe 13 patients with single brain metastasis from prostatic cancer. Total removal of the lesions was performed in ten patients. Three patients underwent stereotactic biopsy. All patients were treated with postoperative whole brain radiotherapy (WBRT). Eight patients died for systemic disease after a mean time of 9.2 months with a diagnosis of metastasis. Five patients are still alive at 20, 14, 11, 7 and 6 months, respectively. Even if brain metastasis from prostate cancer is often a terminal event with death occurring within few months from diagnosis, we suggest the same protocol (surgery and/or radiosurgery plus postoperative WBRT) usually adopted to treat brain metastasis from other primitive tumours. A non specific neurological symptomatology and a possible normal dosage of serum specific antigen may contribute to a delay in diagnosis. However, considering the rarity of brain metastasis from prostate carcinoma, standard brain MRI follow-up in men with prostatic cancer does not seem to be necessary yet.     

Improved outcomes with radiation for prostate cancer

During the last 15 years, a series of substantial technical improvements have occurred in external beam radiation and brachytherapy. The introduction of PSA-based posttreatment monitoring has allowed a reasonable comparison between each radiation modality and prostatectomy. Such comparisons show more similarities than differences. Probably the most exciting finding in regard to curing cancer is that higher-risk patients have a more favorable prognosis than previously recognized using higher doses now achievable with either form of radiation.     

External validation of nomograms for predicting cancer-specific mortality in penile cancer patients treated with definitive surgery

Using a population-based cancer registry, Thuret et al developed 3 nomograms for estimating cancer- specific mortality in men with penile squamous cell carcinoma. In the initial cohort, only 23.0% of the patients were treated with inguinal lymphadenectomy and had pN stage. To generalize the prediction models in clinical practice, we evaluated the performance of the 3 nomograms in a series of penile cancer patients who were treated with definitive surgery. Clinicopathologic information was obtained from 160 M0 penile cancer patients who underwent primary tumor excision and regional lymphadenectomy between 1990 and 2008. The predicted probabilities of cancer-specific mortality were calculated from 3 nomograms that were based on different disease stage definitions and tumor grade. Discrimination, calibration, and clinical usefulness were assessed to compare model performance. The discrimination ability was similar in nomograms using the TNM classification or American Joint Committee on Cancer staging （Harrell＇s concordance index = 0.817 and 0.832, respectively）, whereas it was inferior for the Surveillance, Epidemiology and End Results staging （Harrelrs concordance index = 0.728）. Better agreement with the observed cancer-specific mortality was shown for the model consisting of TNM classification and tumor grade, which also achieved favorable clinical net benefit, with a threshold probability in the range of 0 to 42%. The nomogram consisting of TNM classification and tumor grading was shown to have better performance for predicting cancer-specific mortality in penile cancer patients who underwent definitive surgery. Our data support the integration of this model in decision-making and trial design.     

Ljubljana nomograms for predicting the likelihood of non-sentinel lymph node metastases in breast cancer patients with a positive sentinel lymph node

Several tools for predicting the likelihood of non-sentinel lymph node (non-SLN) involvement in SLN-positive breast cancer patients have been created so far. The aim of our study was to create and validate different nomograms for predicting the likelihood of non-SLN involvement that would be applicable in different institutions and that would also include the results of the preoperative US examination of the axilla. From January 2000 to January 2009, 534 breast cancer patients underwent axillary lymph node dissection (ALND) due to metastatic SLN at our institution. Using logistic regression results three nomograms differing in the inclusion of the results of intraoperative examination of SLN were created. The nomograms were validated using bootstrap methods. In all three nomograms, US examination of the axilla was a powerful independent variable. Other variables included (different in different nomograms) were tumor size, lymphovascular invasion, metastasis size in SLN, number of negative and number of positive SLNs. Mean absolute error and mean area under the ROC curve equals to 0.016 and 0.77 for the first, 0.023 and 0.75 for the second and 0.014 and 0.79 for the third nomogram. Three nomograms for predicting the likelihood of non-SLN metastases including the results of the preoperative US examination of the axilla were created at our institution. They differ in the inclusion of the results of intraoperative examination of SLNs and are thus applicable in different institutions. The validation results seem promising and omission of completion ALND might be considered in patients with the probability of having non-SLN metastases of 10% or less.     

Second-line therapy for castrate-resistant prostate cancer: a literature review

Despite a survival benefit in the first-line treatment of castrate-resistant prostate cancer (CRPC) with docetaxel, the prognosis remains limited. There are increasing options available for patients with CRPC in the second-line setting, but there is currently little consensus regarding the optimal treatment. There have been numerous phase II and retrospective studies examining second-line options in CRPC, including retreatment with docetaxel, mitoxantrone, cyclophosphamide and carboplatin, which can be associated with meaningful responses in a significant minority of patients. In 2010 three randomized trials were published or presented which demonstrated a survival benefit in the second-line setting. These included cabazitaxel compared with mitoxantrone, sipuleucel-T (immunotherapy) and abiraterone acetate versus placebo. Ongoing research in the second-line setting of CRPC to optimize treatment options, with the objectives of survival prolongation, improvement in quality of life and pain management, is still needed.     

Factors associated with initial therapy for clinically localized prostate cancer: prostate cancer outcomes study.

BACKGROUND: Because of the lack of results from randomized clinical trials comparing the efficacy of aggressive therapies with that of more conservative therapies for clinically localized prostate cancer, men and their physicians may select treatments based on other criteria. We examined the association of sociodemographic and clinical characteristics with four management options: radical prostatectomy, radiation therapy, hormonal therapy, and watchful waiting. METHODS: We studied 3073 participants of the Prostate Cancer Outcomes Study diagnosed from October 1, 1994, through October 31, 1995, with clinically localized disease (T1 or T2). Participants completed a baseline survey, and diagnostic and treatment information was abstracted from medical records. Multiple logistic regression analysis identified factors associated with initial treatment. All statistical tests were two-sided. RESULTS: Patients with clinically localized disease received the following treatments: radical prostatectomy (47.6%), radiation therapy (23.4%), hormonal therapy (10.5%), or watchful waiting (18.5%). Men aged 75 years or older more often received conservative treatment (i.e., hormonal therapy alone or watchful waiting; 57.9% of men aged 75-79 years and 82.1% of men aged 80 years and older) than aggressive treatment (i.e., radical prostatectomy or radiation therapy) (for all age groups, P相似文献   

The Anderson nomograms for permanent interstitial prostate implants: a briefing for practitioners

PURPOSE: The objective of this report is to re-evaluate the role of the Anderson nomograms in treatment planning for permanent prostate implants. The incentive for revisiting this topic concerns three issues: (1) Although nomograms continue to be used in many centers for ordering seeds, few centers use them during treatment planning; (2) Whereas nomograms were designed to deliver a minimum peripheral dose for a uniform distribution of seeds in the gland, many practitioners use peripheral seed loading patterns to reduce urethral toxicity; and (3) As preoperative and intraoperative treatment planning is becoming standard, the apparent role of nomograms is diminished. The nomogram method is reviewed in terms of: (1) total activity predicted, (2) target coverage (as planned in the operating room and as calculated from postimplant computed tomography studies), and (3) reproducibility (i.e., patient-to-patient and planner-to-planner variability). In each case, the computer-optimization system for intraoperative planning currently in use at our institution was taken as the "gold standard." METHODS AND MATERIALS: We compared for the same patient the results of nomogram planning to those yielded by genetic algorithm (GA) optimization in terms of total activity predicted (n = 20 cases) and percent target coverage (n = 5 cases). Furthermore, we examined retrospectively the dosimetry of 61 prostate implants planned with the GA (n = 27) and the current implementation of Anderson nomograms (n = 34). RESULTS: Nomogram predictions of the total activity required are in good agreement (within 10%) with the GA-planned activity. However, computer-optimized plans consistently yield superior plans, as reflected in both pre- and postimplant analyses. We find also that user (specifically, treatment planner) implementation of the nomograms may be a major source of variability in nomogram planning-a difficulty to which robust computer optimization is less prone. CONCLUSIONS: Nomograms continue to be useful tools for predicting the total required activity for volume implants, and thus for performing an independent check of this quantity. Not unexpectedly, computer optimization remains the preferred planning method. Generally, nomogram-guided implants do not incorporate structures other than the treatment volume into the planning process. Further yet, they deliver a lower dose than that prescribed and result in greater variability among plans than computer-optimized treatments. In summary, nomograms (1) remain an efficient quality assurance tool for computer-generated plans, (2) serve as a good predictor of the number of seeds required for ordering purposes, and (3) provide a simple and dependable backup planning method in case the intraoperative planning system fails.     

Tissue-based biomarkers predicting outcomes in metastatic colorectal cancer: a review

Although there have been recent advances in the treatment of metastatic colorectal cancer, particularly with systemic chemotherapy, new biological agents and surgical metastasectomy, the disease remains difficult to treat. To personalise the management of mCRC and optimise patient outcomes, it is vital to acquire a deeper understanding of its natural history and mechanisms behind disease progression. This may be achieved by extensive study of tumour biomarkers: proteins or genetic alterations within neoplastic cells or their surrounding stroma that may be used to predict patient outcomes, disease trajectory and response to various therapies. The discovery of mutant Kirsten-RAS in determining patients who may be refractory to anti-epidermal growth factor receptor treatments has reinvigorated and reiterated the importance of our attempts to individualise cancer care. While many biomarkers have been studied and shown promise in the setting of mCRC, they are, with the exception of K-ras testing not used currently in a clinical setting due to conflicting results, small patient samples and methodological variations. Larger, multi-centric studies with uniform methods of tumour marker study are required to effectively tailor systemic therapies and select appropriate candidates for surgical metastasectomy.     

Treatment outcomes in localized prostate cancer: a patient-oriented approach

Although there are many treatment options available to patients with localized prostate cancer, it remains unclear which is superior in terms of overall survival. Patients, therefore, consider a number of other less traditional outcomes when choosing therapy for newly diagnosed disease. In particular, because each treatment can have a unique and highly individual impact on various aspects of the patient's health and daily life, there is a need for a patient-oriented approach to outcomes that accounts for both quantity and quality of life after therapy. Although all therapies can result in some degree of sexual, urinary, or bowel dysfunction, the degree of bother patients experience does not always correlate with the objective degree of symptoms present. Providers must, therefore, make the important distinction between function and bother when presenting the risks for each therapy to patients. Patients should also be aware that if they experience particular bother from their sexual or urinary dysfunction, there are therapies available that will improve erectile function or lower urinary tract voiding dysfunction and result in better quality of life. Finally, when discussing the probability of unwanted outcomes, such as urinary, sexual, or bowel dysfunction after treatment for localized prostate cancer, providers should strive to present risks by using a number of different styles, facilitating understanding, and leading to a truly informed decision that best fits the patient's goals.     

Comparison of endorectal magnetic resonance imaging, clinical prognostic factors and nomograms in the local staging of prostate cancer patients treated with radiotherapy

AIMS AND BACKGROUND: To determine retrospectively the role of endorectal magnetic resonance in the staging of prostate cancer. The aim of the study was to assess whether it is possible to identify a group of patients with prostate cancer, chosen for certain prognostic factors, eligible for radiotherapy that could take advantage of endorectal magnetic resonance in staging and therapy management. METHODS: Between January 2002 and December 2005, 143 patients with biopsy proven prostate cancer underwent endorectal magnetic resonance. All patients were initially evaluated considering the following prognostic factors: serum prostate-specific antigen at diagnosis, Gleason score, histological grade, involvement of the seminal vesicle and extracapsular extension using the Roach III and ECE equations. The findings were then compared to the results of endorectal magnetic resonance. RESULTS: The relationship between the variable post-endorectal magnetic resonance stage modification and Gleason score was statistically significant (P = 0.02847). In addition, our study showed a statistically significant correlation between the risk of seminal vesicle involvement according to the Roach III formula and post-endorectal magnetic resonance stage modification (P = 0.01305). Conversely, statistical analysis showed no significant correlation between post-endorectal magnetic resonance stage modification and prostate-specific antigen values (P = 0.83440) or between post-endorectal magnetic resonance stage modification and the risk of extracapsular extension according to the extracapsular extension formula (P = 0.42748). CONCLUSIONS: Our data suggest that endorectal magnetic resonance could be used for staging of the subgroup of patients at high risk of seminal vesicle involvement (> 15%). Although we found a statistical correlation between Gleason score and post-endorectal magnetic resonance stage modification, statistical analysis showed no correlation between any of the subgroups. Therefore, it is not possible at the moment to identify a subgroup of patients by Gleason score that may benefit from endorectal magnetic resonance. In our opinion, extracapsular extension values were not useful to select patients for endorectal magnetic resonance.