Incidental Axillary Lymphadenopathy Found on Radiation Planning Computed Tomography.

PURPOSE: The aim of this study was to evaluate the rate of axillary node-positive disease in patients with early breast cancer who had a suspicious axillary lymph node on radiation planning computed tomography (CT). METHODS AND MATERIALS: A retrospective review was conducted of the medical records of all patients with breast cancer who were referred for axillary ultrasound from the radiation unit to the breast imaging unit at the Meirav Breast Center, Sheba Medical Center, from 2012 to 2022. Ethics approval was obtained. Only the records of patients who were referred due to an abnormal axillary lymph node seen on radiation planning CT were further evaluated. RESULTS: During the study period, a total of 21 patients were referred to the breast imaging unit for evaluation of suspicious nodes seen on radiation planning CT. Of these, 3 cases were excluded. A total of 15 out of the 18 (83%) patients included had an abnormal lymph node in the ultrasound, and an ultrasound-guided biopsy was recommended (BI-RADS 4). Of these, 3 (out of 15, 20%) had a positive biopsy for tumor cells from the axillary lymph node. Two were cases after primary systemic therapy without complete pathologic response. Thickening of the lymph node cortex and complete loss of the central fatty hilum were associated with pathologic lymph node. CONCLUSION: Sonar had limited ability to differentiate reactive nodes from involved nodes. The presence of lymph nodes with loss of cortical-hilum differentiation on ultrasound together with clinical features are parameters that can help guide the need of further biopsy. Histopathology evaluation is important to make the diagnosis of residual axillary disease. Future studies and guidelines are needed to improve the diagnostic abilities and reduce the number of patients who are undergoing biopsy for noninvolved nodes.

The Coming of Age of Breast Radiotherapy.

Exactly 50 years ago, the investigators of the National Surgical Adjuvant Breast and Bowel Project began to design the B-06 trial [...].

[INTRAOPERATIVE RADIOTHERAPY FOR EARLY BREAST CANCER - THE SHEBA EXPERIENCE AND EARLY OUTCOMES].

AIMS: This study presents our experience with Intra-Operative Electron Radio-Therapy (IOeRT) using a mobile linear accelerator at the Sheba Medical Center. BACKGROUND: Intraoperative radiotherapy is an alternative approach of partial breast irradiation for patients with early breast cancer and low risk for local recurrence who are undergoing breast conservation surgery. METHODS: Patients were selected by a multidisciplinary team according to ASTRO\GEC-ESTRO guidelines for partial breast irradiation. IOeRT was administered using SIT LIAC HWL®. RESULTS: A total of 28 patients were referred for breast conservation surgery and IOeRT between 8/2019 and 10/2020; 27/28 received IOeRT. In one patient, radiation was aborted due to anaphylactic shock in response to patent blue dye injected for sentinel node identification. Larger than usual seroma were reported on the first post-operative visit in all patients, and regressed spontaneously in 3-6 months. Infected seroma developed post-operatively in 5 patients, requiring surgical drainage in 2 patients. Final pathology matched the preoperative biopsy. There were no cases of pathology upstaging requiring additional adjuvant irradiation or chemotherapy. The patient who did not receive IOeRT was treated with adjuvant external radiotherapy. CONCLUSIONS: IOeRT is a safe alternative to partial breast irradiation, with a slight increase of postoperative infection rate.

Attention Dysregulation in Breast Cancer Patients Following a Complementary Alternative Treatment Routine: A Double-Blind Randomized Trial.

INTRODUCTION: Breast cancer patients and survivors frequently report fatigue, emotional, and cognitive disturbances, which reduce performance at all levels of occupation and make life quality issues a considerable clinical concern. The aim of this study is to evaluate attention and emotion regulation across radiotherapy period and the possible effects of complementary alternative medicine (CAM). METHODS: Fifty-seven patients with unilateral breast cancer underwent surgery and systemic chemotherapy before participating in this double-blind randomized study. Two thirds were given CAM (n = 38) while the rest received placebo (carrier only, n = 19). Patients' attention and anxiety were physiologically tested at baseline, 2 and 4 weeks during the radiation period as well as 1-month after the end of radiation session. RESULTS: Both groups showed similar levels of anxiety with no significant differences at baseline nor post-radiotherapy. Long-term significant recovery of attention performance was observed in the CAM patients, accompanied by a similar tendency in anxiety level, measured by the eye-blink probability. CONCLUSIONS: This study physiologically validates the attention impairment reported among breast cancer survivors; also, it depicted a beneficial late-effect of a routine CAM on attention dysregulation. The suggested non-invasive physiological measures can physiologically monitor patients' psychological and cognitive well-being as well as evaluate the beneficial effect of CAM in breast cancer patients by assessing their coping ability to support the treatment plan. Thus, the results have potential clinical implications on patients' and survivors' quality of life. TRIAL REGISTRATION: NIH, NCT02890316. Registered July 2016, http://www.ClinicalTrials.gov.

Benefits of Continuous Positive Airway Pressure (CPAP) During Radiation Therapy: A Prospective Trial.

PURPOSE: This study aimed to study the impact of continuous positive airway pressure (CPAP) on chest anatomy and tumor motion in patients receiving radiation therapy. METHODS AND MATERIALS: Patients with primary or secondary lung tumors, left-sided breast cancer, or liver metastases referred for radiation therapy were trained to breathe with a CPAP device using a face mask to a maximal pressure of 15 cm H2O. Three- and 4-dimensional computed tomography simulation was performed twice for each patient: once with free breathing (FB) and again using CPAP. Volumetric and dosimetric parameters of treatment plans were compared. RESULTS: Forty-nine patients were enrolled, of whom 6 withdrew consent before simulation and 3 withdrew because of discomfort. Thus, a total of 40 patients were analyzed. Twenty-seven patients (67.5%) were treated with CPAP based on confirmation of the volumetric or dosimetric benefit of CPAP. Mean lung volume increased by 37% (P < .001). The mean augmentation was 1283 ± 1128 cm3 (CPAP vs FB; P = .0006) in patients with normal lung function tests and 719 ± 341 cm3 (P = .003) in patients with a restrictive pattern. Increased lung volume was independent of age, body mass index, sex, chronic obstructive pulmonary disease, smoking status, and heart disease. Tumor motion in the lung was decreased as reflected in a mean reduction of planning target volume by 19% (P < .001). The greatest reduction of tumor trajectory and planning target volume occurred in tumors in the lower lung, particularly in the range of up to 6 cm above the dome of the diaphragm. The mean lung dose was reduced by 15%, lung V20 by 20%, lung V5 by 11%, and heart V5 by 16% (P < .01). CONCLUSIONS: In this prospective trial, the use of CPAP was associated with significant volumetric and dosimetric benefits compared with FB. CPAP was safe, simple to implement, and well tolerated by most patients, and it should be studied further as a method to reduce the risk of lung and heart toxicity.

Palliative radiation therapy for symptomatic advance breast cancer.

In this study, we evaluated the effectiveness of palliative breast radiation therapy (RT), with single fraction RT compared with fractionated RT. Our study showed that both RT fractionation schemas provide palliation. Single fraction RT allowed for treatment with minimal interference with systemic therapy, whereas fractionated RT provided a more durable palliative response. Due to equivalent palliative response, at our institution we have increasingly been providing single fraction RT palliation during the COVID-19 pandemic.

Continuous positive airway pressure with deep inspiration breath hold in left-sided breast radiation therapy.

A dosimetric study to evaluate the use of continuous positive airway pressure (CPAP), with free-breathing (CPAP-FB) or with deep inspiration breath hold (DIBH-CPAP) an adjunct and alternative to DIBH to reduce heart and lung dose in the radiation therapy (RT) of breast cancer planned for left side RT with regional nodes and internal mammary. A retrospective analysis of 10 left-sided breast cancer patients whose heart or lung dose constraints were not met after RT planning based on FB or DIBH simulations and were referred for CPAP-based planning. All patients were simulated using FB, DIBH, CPAP-FB, and CPAP-DIBH. Treatment plans were calculated to cover the breast/chest wall and regional nodes using tangential field-in-field technique (FiF). Dose-volume parameters for heart, ipsilateral lung, and contralateral breast were compared using the Wilcoxon signed-rank test. For all RT plans, mean heart dose (Gy) was lower for treatment plans with CPAP: CPAP-FB (mean 3.4 vs 7.4, p = 0.001) and CPAP-DIBH (mean 2.5 vs 7.4, p = 0.006) compared to FB alone. CPAP-DIBH also significantly reduced MHD as compared to DIBH alone (mean 2.5 vs 4.3 Gy, p = 0.013). CPAP-DIBH significantly reduced mean lung dose as compared to both FB (mean 14.4 vs 20.1, p = 0.005) and DIBH alone (mean 14.4 vs 17.4, p = 0.007). Eight of 10 patients did not meet ipsilateral lung V20Gy dose constraints (≥35% of lung receiving 20 Gy) in either the free breathing or DIBH plans, whereas 8 out of 10 met lung V20Gy goal constraints (≤30% of lung receiving 20 Gy) in the CPAP-DIBH plans. Based on the outcomes of our study, CPAP could be a strategy for reducing lung and heart dose, both in patients not able to execute DIBH and as an adjunct in those not deriving sufficient dose reduction from DIBH alone.

Locoregional Treatments and Ipsilateral Breast Cancer Recurrence Rates in BRCA1/2 Mutation Carriers.

PURPOSE: There is a paucity of data on the rates of ipsilateral breast tumor recurrence (IBTR) in BRCA1/2-associated breast cancer (BC). Scarcer yet are outcomes data in BRCA1/2 mutation carriers in the setting of newer mastectomy techniques, such as skin-sparing mastectomies (SSM) and nipple-sparing mastectomies (NSM). METHODS: Data were extracted from the medical records of BRCA1/2 carriers who were diagnosed with BC and treated at a single institution between 2006 and 2020. The data extracted included patient demographics, tumor characteristics, disease stage, surgical treatment, use of radiation therapy (RT), and disease outcome. RESULTS: Overall, 255 BC patients with BRCA1/2 germline mutations were identified. Of these, 128 (50.2%) underwent a mastectomy (SSM or NSM in 82% of them), 76 (59.4%) without postmastectomy RT (non-PMRT) and 52 (40.6%) with PMRT, whereas 127 (49.8%) elected for breast-conserving treatment (BCT). The non-PMRT group had earlier disease stages (82.3% were Tis and T1N0) compared with the PMRT and BCT groups (3.6% and 48.1%, respectively; P < .05). The IBTR cumulative rate was 9 of 76 (11.8%) in the non-PMRT cohort compared with 0 of 52 in the PMRT group (P = .01) and 6 of 127 (4.7%) in the BCT group (P = .06). The cumulative incidences of IBTR at 5 and 10 years were 9.8% and 27.4%, respectively, in the non-PMRT group versus 2% and 11.3%, respectively, in the BCT group (P = .0183). No significant difference in overall survival was observed at the time of follow-up. CONCLUSIONS: BRCA1/2 mutation carriers treated with mastectomy without PMRT had higher rates of IBTR than those who underwent mastectomy and PMRT or BCT, despite earlier stages of disease. The safety of SSM/NSM should be evaluated in a prospective trial.

Radiation-Associated Secondary Malignancies in BRCA Mutation Carriers Treated for Breast Cancer.

PURPOSE: Radiation therapy (RT), a standard breast cancer (BC) treatment modality, is associated with a small increased risk of in-field second primary malignancy (SPM). SPM rates after RT in BRCA mutation carriers have rarely been reported. An elevated risk of SPM would affect the safety of breast conservation for early BC or prophylactic radiation as a method of prevention. We analyzed a population of BRCA carriers irradiated for BC to determine whether there is an elevated rate of SPM. METHODS AND MATERIALS: Patients with BC who were BRCA1 or BRCA2 carriers and were treated with breast and/or chest wall RT with or without regional lymph nodes between 1991 and 2012 at a single institution were retrospectively identified. Only those with ≥5 years of follow-up with adequate demographic, tumor, and radiation data were included. SPMs were recorded, and previously delivered RT doses to the organ and site of malignancy were determined. RESULTS: Two hundred thirty women, of whom 80% carried an Ashkenazi Jewish founder mutation, met entry criteria with 3-dimensional RT delivered to 266 breasts or chest walls, including regional nodes in 110 (41%). With a median follow-up of 10 years (range, 5-27; mean 11.4) comprising 3042 person-years, 6 SPMs developed, of which only 1 (papillary thyroid carcinoma) was within the radiation field (crude rate of 0.38% of irradiated breasts or chest walls), diagnosed 17 years after RT. This corresponds to an incidence of 0.32 per 1000 woman-years. The Kaplan-Meier estimate of 20-year freedom from a radiation-induced SPM is 99.5%. Calculated dose exposure to the out-of-field SPMs ranged from 0.1 to 1 Gy. No patient developed an in-field skin cancer or sarcoma. CONCLUSIONS: In this largest cohort of women treated with radiation therapy for BRCA-associated breast cancer, we identified no signal for an increased risk of radiation-induced SPMs compared with the general BC population, and the risk is extraordinarily small. Although larger cohorts and longer follow-up are needed, these results support the safety of RT in BRCA carriers.

Local recurrence of breast cancer: Salvage lumpectomy as an option for local treatment.

INTRODUCTION: The best local management for breast cancer recurrence following conservative treatment for breast cancer (BC) continues to be an open question. In this study, we compared patients' outcome after salvage lumpectomy (SL) vs mastectomy for ipsilateral breast tumor recurrence (IBTR). MATERIALS AND METHODS: Between 1987 and 2014 we identified 121 patients with pT0-2, N0-3, M0 BC who had BCT as their primary treatment, and subsequently had IBTR (unifocal). 47 patients underwent SL and 74 salvage mastectomy (SM) as the local treatment for their 1st recurrence. RESULTS: Median follow-up was 14 years (1-30) from first BC diagnosis. For the SL and SM cohorts, 8 and 10 patients (17%, 13.5%, P = 0.22), respectively, developed subsequent local recurrence as a 3rd event. Although in MVA, woman who underwent SL had higher chances of having a 2nd recurrence (3rd event), P = 0.020, at a median follow-up of 14 years, 95.8% of SL patients are alive, NED, 85% are mastectomy free. 87% of patients who opted for SM are alive, NED. Having re-irradiation following SL did not protect against 2nd breast cancer recurrence (3rd event, P = 0.42). CONCLUSION: Salvage lumpectomy following IBTR, while associated with higher second LR rate than SM is not associated with inferior outcome. With survival >95% at 14 years in the SL cohort, salvage lumpectomy with or without re-radiation, in a selected population (unifocal T), represents an acceptable treatment option for patients in order to delay time to mastectomy without reducing BC survival. Both options should be discussed prior to any surgical decision.

RPM Inspiration Gating: Improving Radiotherapy for Left Breast Cancer Patients with Anterior Heart Position.

BACKGROUND: Adjuvant radiotherapy for breast cancer reduces local recurrence and improves survival. In patients with left sided breast cancer, anterior heart position or medial tumor location may cause inadequate breast coverage due to heart shielding. Respiration gating using the Real-time Position Management (RPM) system enables pushing the heart away from the tangential fields during inspiration, thus optimizing the treatment plan. OBJECTIVES: To compare breathing inspiration gating (IG) techniques with free breathing (FB), focusing on breast coverage. METHODS: The study comprised 49 consecutive patients with left sided breast cancer who underwent lumpectomy and adjuvant radiation. RPM was chosen due to insufficient breast coverage caused by an anterior heart position or medial lumpectomy cavity. FB and IG computed tomography simulations were generated for each patient. Breast (PTVbreast) and lumpectomy cavity (CTVlump) were defined as the target areas. Optimized treatment plans were created for each scan. A dosimetric comparison was made for breast coverage and heart and lungs doses. RESULTS: PTVbreast V95% and mean dose (Dmean) were higher with IG vs. FB (82.36% vs. 78.88%, P = 0.002; 95.73% vs. 93.63%, P < 0.001, respectively). CTVlump V95% and Dmean were higher with IG (98.87% vs. 88.92%, P = 0.001; 99.14% vs. 96.73%, P = 0.003, respectively). The cardiac dose was lower with IG. The IG left lung Dmean was higher. No statistical difference was found for left lung V20. CONCLUSIONS: In patients with suboptimal treatment plans due to anterior heart position or medial lumpectomy cavity, RPM IG enabled better breast/tumor bed coverage and reduced cardiac doses.

Use of 18F-FDG PET-CT imaging to determine internal mammary lymph node location for radiation therapy treatment planning in breast cancer patients.

PURPOSE: Adjuvant internal mammary lymph node (IMN) radiation is often delivered with 2-dimensional techniques that use anatomic landmarks and predetermined depths for field placement and dose specification. In contrast, 3-dimensional planning uses the internal mammary vessels (IMVs) to localize the IMNs for planning. Our purpose was to determine if localization of the involved IMN (i-IMN) by 18F-labeled fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET-CT) offers opportunities to improve treatment. METHODS AND MATERIALS: Breast cancer patients (n = 80) who had i-IMNs (n = 112) on PET-CT for initial staging (n = 40) or recurrence (n = 40) were studied. Size, intercostal space (IC), and distance from skin, sternum, and IMVs were recorded. Effects on 2- and 3-dimensional planning were evaluated. RESULTS: Most i-IMNs (94.6%) were in the first to third ICs. Few were in the fourth (4.5%) or fifth (0.9%) IC. Mean i-IMN depth was 3.4 cm (range, 1.1-7.3 cm). Prescriptive depths of 4, 5, and 6 cm would result in undertreatment of 25%, 10.7%, and 5.3% of IMNs, respectively. Most IMNs (86.6%) were lateral or adjacent to the sternal edge. Only 13.4% of IMNs were posterior to the sternum. Use of the ipsilateral or contralateral sternal edge for field placement increases the risk of geographic miss or excess normal tissue exposure. Most i-IMNs were adjacent to (83%) or ≤0.5 cm (14%) from the IMV edge. Three (3%) were >0.5 cm beyond the IMV edge. The clinical target volume (CTV) defined by the first to third ICs encompassed 78% of i-IMNs. IMN-CTV coverage of i-IMNs increased with inclusion of the fourth IC (82%), 0.5 cm medial and lateral margin expansion (93%), or both (96.5%). CONCLUSION: Two-dimensional treatment techniques risk geographic miss of IMNs and exposure of excess normal tissue to radiation. An IMN-CTV defined by the IMVs from the first to third ICs with 0.5-cm medial and lateral margin expansion encompasses almost all i-IMNs identified on PET-CT imaging. Inclusion of the fourth IC offers modest coverage improvement, and its inclusion should be weighed against potential increase in cardiac exposure. SUMMARY: The use of 2-dimensional treatment techniques for adjuvant internal mammary lymph node (IMN) radiation may cause geographic miss of tumor and expose normal tissue to radiation injury. Conformal 3-dimensional planning improves coverage and reduces risk of normal tissue damage by using the internal mammary vessel to define an IMN clinical target volume (CTV). Contouring the IMN-CTV from the first to third intercostal spaces with a 0.5-cm expansion medially and laterally encompasses most IMN. Positron emission tomography-computed tomography may have a role in radiation planning by identifying involved-IMN for dose escalation.

Clinically significant cardiac disease in patients with Hodgkin lymphoma treated with mediastinal irradiation.

This study assessed the cumulative incidence of clinically significant cardiac disease in 1279 Hodgkin lymphoma patients treated with mediastinal irradiation and quantified the standard incidence ratios (SIRs) and absolute excess risks of cardiac procedures compared with a normal matched population. Cox regression analysis was used to explore factors associated with cardiac complications. Poisson regression analysis of SIRs was used to estimate the excess risk of cardiac interventions from mediastinal irradiation. After a median follow-up of 14.7 years, 187 patients experienced 636 cardiac events and 89 patients required a cardiac procedure. 5-, 10-, 15-, and 20-year cumulative incidence rates of cardiac events were 2.2%, 4.5%, 9.6%, and 16%. SIRs for cardiac procedures were increased for coronary artery bypass graft (3.19), percutaneous intervention (1.55), implantable cardioverter defibrillator or pacemaker placement (1.9), valve surgery (9.19), and pericardial surgery (12.91). Absolute excess risks were 18.2, 19.3, 9.4, 14.1, and 4.7 per 10 000 person-years, respectively. Older age at diagnosis and male sex were predictors for cardiac events. However, younger age at diagnosis was associated with excess risk specifically from radiation therapy compared with the general population. These results may help guideline development for both the types and timing of cardiac surveillance in survivors of Hodgkin lymphoma.

Diagnosis and management of mycosis fungoides.

Mycosis fungoides (MF), the most common cutaneous T-cell lymphoma, is a low-grade cutaneous lymphoma characterized by skin-homing CD4+ T cells. It is notable for highly symptomatic progressive skin lesions, including patches, plaques, tumors, and erytheroderma, and has a poorer prognosis at later stages. Diagnosis remains difficult owing to MF's nonspecific skin presentation and identification of the optimal treatment strategy is challenging given the paucity of controlled trials and numerous and emerging treatment options. Management includes topical therapy with the addition of systemic therapy for patients with later-stage disease including tumors; erythroderma; and nodal, visceral, or blood involvement. Topical therapies include mechlorethamine (nitrogen mustard), carmustine (BCNU), steroids, bexarotene gel (Targretin Gel), psoralen plus ultraviolet A (PUVA), ultraviolet B (UVB), and either localized or total skin electron radiotherapy. Systemic therapies include interferon, retinoids, oral bexarotene (Targretin), denileukin diftitox (Ontak), vorinostat (Zolinza), extracorporeal photochemotherapy (photopheresis), and cytotoxic chemotherapy. Herein, we outline clinically relevant aspects of MF, including clinical presentation, pathology, diagnosis, and staging. We describe in detail existing and emerging therapeutics and offer specific recommendations for management of each stage of MF.

An attempt to independently verify the utility of the Van Nuys Prognostic Index for ductal carcinoma in situ.

BACKGROUND: The Van Nuys Prognostic Index (VNPI) purports to predict the risk of ipsilateral breast tumor recurrence (IBTR) after excision of ductal carcinoma in situ (DCIS). It is a simple scoring scheme based on a retrospective evaluation of data from a single group of investigators. Various versions of VNPI have been proposed using clinical and pathologic features including tumor size, tumor grade, margin width, and patient age. Despite common use of VNPI in the clinical management of patients with DCIS, independent validation is lacking. METHODS: A total of 222 patients were retrospectively analyzed with mammographically detected DCIS who were treated with surgical excision alone. Wire-localized excisional biopsy was performed and surgical specimens were measured and inked to assist in margin assessment. Multiple sections of each specimen were evaluated for histopathologic subtype, histologic and nuclear grade, presence of necrosis, maximum dimension of the lesion, and margin width. Each patient was prospectively evaluated by a multidisciplinary management team and presented with adjuvant treatment options including whole breast radiotherapy and/or tamoxifen. All patients in this cohort declined radiotherapy. Thirty-one percent of patients received tamoxifen. Patients were followed clinically every 3 to 6 months, and mammographically every 6 to 12 months. IBTR was confirmed by biopsy. Wilcoxon regression analysis was used to evaluate risk groups according to 3 proposed VNPI classification schemes: VNPI Group 1 (margin, grade, and size), VNPI Group 2 (margin, grade, size, and patient age), and VNPI Group 3 (margin only). RESULTS: With a median follow-up of 4.6 years, the crude rate of IBTR was 8.6% for the entire cohort. Of the patients who developed an IBTR, 73.7% had a lesion with a maximum dimension of < or =15 mm, 47.4% had a margin > or =10 mm, and 36.8% had grade 1 histology. At 5 years, IBTR was statistically indistinguishable for the 3 VNPI models. The 5-year freedom from IBTR for low-risk, intermediate-risk, and high-risk groups according to VNPI Group 1 was 96%, 84%, and 100%, respectively (P = .20). Similarly, the 5-year freedom from IBTR for low-risk, intermediate-risk, and high-risk groups according to VNPI Group 2 was 95%, 83%, and 100%, respectively (P = .19). Taking into account margin status only (VNPI Group 3) the 5-year freedom from IBTR for low-risk, intermediate-risk, and high-risk groups was 92%, 91%, and 91%, respectively (P = .98). Tamoxifen use did not appear to affect the 5-year rate of IBTR (95% vs 94%; P = 1.0). CONCLUSIONS: The results of the current study suggest that VNPI or margin width alone is not a valid tool with which to assist in the stratification of patients after excision alone for their risk of IBTR at 5 years. Further follow-up may strengthen the predictive utility of the various VNPI classification schemes.

Evidence to support a continued stage migration and decrease in prostate cancer specific mortality.

PURPOSE: We evaluated whether the proportion of patients with a postoperative PSA-DT less than 3 months, a surrogate for PCSM, decreased significantly during the PSA era. MATERIALS AND METHODS: Between July 1988 and July 2002, 3,719 men with clinically localized prostate cancer treated with RP comprised the study cohort. A chi-square metric was used to compare the preoperative and postoperative characteristics, 5-year actual PSA failure rates, and PSA-DTs for patients treated during the 2 equally divided eras of the early PSA era, July 1988 to July 1995 and the late PSA era, August 1995 to July 2002. RESULTS: Patients presenting in the more recent PSA era were of younger age (p < 0.0001), with earlier stage (p < 0.0001) and lower grade disease (p = 0.01). Similarly, patients had lower grade (p < 0.001), stage (p < 0.0001), and positive margin (p < 0.0001) and lymph node rates (p = 0.0002) at RP. The 5-year actual PSA failure rates decreased from 14.3% in the early PSA era to 2.5% in the later PSA era (p < 0.0001). There was a 37% reduction in the proportion of patients with a PSA-DT less than 3 months, corresponding to a decrease in absolute magnitude from 9% to 5.7% between the 2 eras. Absolute reductions of 3.1% and 9% were also noted for the proportion of PSA-DTs of 3 to 5.99 months and 6 to 11.99 months, respectively, whereas PSA-DTs of 12 months or greater increased by 15.3%. CONCLUSIONS: During the recent PSA era, postoperative PSA failure has significantly decreased and PSA-DTs have increased, suggesting that PCSM will continue to decrease.