Objective To validate established postoperative nomograms in a patient population with long-term follow-up. There are well-documented risk factors that can help predict for failure after radical ...prostatectomy for prostate cancer. When combined together, the predictive power is greater than any single factor. It now appears that the most powerful tool in this regard is the nomogram because it considers the various factors as continuous variables. Materials and Methods The original postoperative nomogram was developed in 1999 and modified and updated in 2005. A slightly modified version was published in 2009. We evaluated these nomograms against a large (n = 715) post–radical prostatectomy patient population with long-term follow-up (median 9.4 years). Results The concordance index for the 1999, 2005, and 2009 nomograms was 0.7831, 0.7680, and 0.7859. From plots of the calibration curves in each nomogram, the nomogram underestimated the actual 10-year biochemical recurrence risk in our patient population. Conclusions Nomograms dynamically incorporate various risk factors and account for their interrelationships. Our findings confirm that the nomograms are predictive in an external patient population with an accuracy of >70%. The predictive ability of nomograms will be improved with the development of other predictive factors, which will most likely occur through the development of molecular markers.
Historically advanced prostate cancer had been treated with androgen ablation. With the evolution of radiation therapy it was shown that some patients with advanced but nonmetastatic disease could be ...cured or at least have progression delayed. Subsequently a series of studies demonstrated that the combination of radiation and androgen ablation resulted in improved results over those of radiation therapy alone, although the failure rate was still high. This review explores the continued evolution in the treatment of high risk disease.
The published literature on treatment for high risk prostate cancer was reviewed.
Adding androgen ablation to radiation decreased the failure rate from 79% to 67% in older studies and 55% to 25% in more recent studies. Most contemporary studies of higher radiation doses showed further improvement with a failure rate of 20% to 40%. The results of adding an implant boost appears to have decreased the failure rate further to 30% or less in most studies. There is now great interest in exploring chemotherapy or biological agents as adjuvant therapy to try to improve the results further. The role of surgery in these patients is also awaiting further clarification.
Radiation therapy has been the primary mode of curative therapy for high risk prostate cancer for 3 decades. Much progress has been made. Evolving data suggest that radiation will continue to have the primary role in treatment in these patients in the future.
Micro-Abstract Because they are commonly involved and easily sampled, lymph nodes along the obturator artery are often considered to be representative of the lymph node status of patients with ...prostate cancer. We performed a comprehensive review of the historical anatomic descriptions in conjunction with modern imaging and surgical information, and this characterization appears an oversimplification and may actually be misleading.
We sought to evaluate the effect of radiation therapy on post-prostatectomy urinary quality of life in prostate cancer patients.
In some men with non-metastatic prostate cancer, radiation therapy is ...indicated following prostatectomy. The radiation toxicity and quality of life considerations are unique in the post-prostatectomy setting.
A total of 106 patients receiving post-prostatectomy radiation therapy completed the Expanded Prostate Cancer Index Composite questionnaire before radiation and at 2-year follow-up. The primary outcomes of this study were the urinary domain summary score and subscale scores. Planned analysis was performed based on time interval from prostatectomy to radiation therapy.
Among the 106 patients analyzed, the mean urinary domain summary score worsened at 2-year follow-up after radiation therapy, lowering from 77.23–72.51 (p = 0.0085). Similar worsening was observed in the subscales of function (p = 0.003), bother (p = 0.0397), and incontinence (p = 0.0003). Urinary incontinence showed the greatest observable change among subscales. While the summary score worsened (p = 0.0031) among patients receiving radiation therapy more than 1 year after prostatectomy, it did not show statistically significant change in those treated 1 year or less after prostatectomy.
Our results demonstrate that post-prostatectomy radiation therapy is associated with modest declines in reportable urinary quality of life. Patients receiving radiation therapy more than 1 year after prostatectomy showed greater worsening of urinary quality of life, which indicates that there may be no functional advantage to delaying radiation therapy beyond the initial postoperative period.
Prostate dose escalation appears to have resulted in increased cancer control. Such escalation has been made possible by the ability to deliver more conformal treatment that spares normal tissue from ...the higher radiation doses. The supposition is that this has enabled higher doses, but without an increase in toxicity. The most disabling toxicity in prostate cancer radiotherapy is rectal. We evaluated the current status of conformal radiation and late rectal toxicity with the goal of determining whether reasonable rectal dose and volume constraints can be determined. Although the literature is inexact, we believe that some generalized constraints can be recommended and show that those recommendations are consistent with what is being used at experienced centers.
Objectives: To review our two institutional experiences regarding the historical referral patterns of bladder cancer patients to receive radiation therapy, characteristics of these referred patients, ...and their treatment outcomes. Methods: A retrospective review was performed analyzing patients who underwent radiation therapy for bladder cancer from 2005 to 2015 (n = 69) at two regional referral institutions. The age-adjusted Charlson comorbidity index (AACCI) was calculated for each patient. Patients were divided into three groups: definitive concurrent chemoradiation (CCR), aggressive radiation (AR) alone ≥ 50 Gy, or palliative radiation alone (PR) < 50 Gy. Gastrointestinal (GI) and genitourinary (GU) acute toxicities were recorded. Results: The median overall AACCI score was 7, which correlates to a two-year expected survival of 55% ± 11%. Thirty-five (50.7%) patients received CCR, 19 (27.5%) received AR, and 15 (21.7%) received PR. Patients presented with hematuria (n = 43, 62%), pain (n = 18, 26%), or obstruction (n = 12, 17%). Of symptomatic patients, treatment improved hematuria in 86%, pain in 75%, and obstruction in 42%. Twenty-two recurrences (32%) were identified at follow-up. Local, regional, and distant recurrences developed in 20%, 14%, and 17% of patients who received CCR. There were two grade 3 GU toxicities and one grade 3 GI toxicity; all grade 3 toxicities were in patients receiving CCR. Conclusions: Bladder preservation is possible with chemoradiation therapy; however, urologists rarely refer patients for consideration of chemoradiation. The limited patients who are referred for radiation generally have limited life expectancy, significant comorbidities, or have advanced disease amenable only to palliation. Palliative radiation improves symptoms with minimal toxicity.
Randomized studies have established wide excision and radiation as an equal alternative to mastectomy in the treatment of breast cancer. The early studies mandated pathologically negative margins for ...those undergoing radiation. The absolute necessity of free margins is uncertain. We evaluated our experience and outcome with breast-conserving surgery and radiation in relation to margin status. Two hundred sixty patients underwent wide excision for breast-conserving therapy for breast cancer. Reexcision was performed in 149 patients. The initial margin status was correlated with the amount of residual found on reexcision and the effect on local failure. The incidence of residual disease on reexcision in patients with initial gross margin involvement, focal margin involvement, and free margins was 30%. Patients with multiple margin positivity had a 65% incidence of residual disease. Only 9% (14/149) of the reexcised patients had more than 3 mm of residual cancer. This was more likely, but not significant, in those with initial margin involvement (11/100 or 11%) than in those with free margins (3/49 or 6%, p= 0.49). The risk of subsequent local failure was 8% (12/143) in those with initial free margins and 5% (6/117) in those with initial margin involvement. Those who had any residual tumor on reexcision had a nonsignificant risk of local failure (13%) compared to those that had no residual on reexcision (4%). Positive margin on initial excision is only slightly more likely to predict for residual cancer than the finding of negative margins. Routine reexcision of patients with positive margins does not significantly increase the chance of local control in patients who receive breast irradiation.
p53 activation is a primary mechanism underlying pathological responses to DNA damaging agents such as chemotherapy and radiotherapy. Our recent animal studies showed that low dose arsenic ...(LDA)-induced transient p53 inhibition selectively protected normal tissues from chemotherapy-induced toxicity.
Study objectives were to: 1) define the lowest safe dose of arsenic trioxide that transiently blocks p53 activation in patients and 2) assess the potential of LDA to decrease hematological toxicity from chemotherapy.
Patients scheduled to receive minimum 4 cycles of myelosuppressive chemotherapy were eligible. For objective 1, dose escalation of LDA started at 0.005 mg/kg/day for 3 days. This dose satisfied objective 1 and was administered before chemotherapy cycles 2, 4, and 6 for objective 2. p53 level in peripheral lymphocytes was measured on day 1 of each cycle by ELISA assay. Chemotherapy cycles 1, 3, and 5 served as the baseline for the subsequent cycles of 2, 4, and 6 respectively. If p53 level for the subsequent cycle was lower (or higher) than the baseline cycle, p53 was defined as “suppressed” (or “activated”) for the pair of cycles. Repeated measures linear models of CBC in terms of day, cycle, p53 activity and interaction terms were used.
Twenty-six patients treated with 3 week cycle regimens form the base of analyses. The mean white blood cell, hemoglobin and absolute neutrophil counts were significantly higher in the “suppressed” relative to the “activated” group.
These data support the proof of principle that suppression of p53 could lead to protection of bone marrow in patients receiving chemotherapy.
This trial is registered in ClinicalTrials.gov. Identifier: NCT01428128.
•p53 activation is a major pathway for pathological response to DNA damaging agents.•This p53 pathway is independent of tumor suppressor pathway of p53.•Suppression of this pathway selectively protects normal tissue, not cancer, in vivo.•We found arsenic dose that temporarily and reversibly suppresses this pathway in man.•Successful suppression of p53 leads to protection of bone marrow from chemotherapy.
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