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Objective: To identify factors associated with regional recurrence after lymph node dissection (LND) for squamous cell carcinoma (SCC) to determine which patients might benefit from adjuvant therapy., Patients and Methods: Men who underwent LND for penile SCC from 1977 to 2014 were identified from an institutional database. Kaplan-Meier curves estimated recurrence-free survival (RFS) calculated from the date of LND. Cox regression models evaluated the association between RFS and patient and tumour characteristics., Results: In all, 182 men who underwent LND for penile SCC were identified. The median patient age was 62 years and the median follow-up was 4.2 years. After LND 34 men had regional recurrence, of which 24 developed isolated regional recurrences without distant metastasis. The median RFS was 5.7 months, and the 3-year RFS rate was 70%. On univariate analysis, lymphovascular invasion, clinical and pathological nodal stage, pathological inguinal laterality, pelvic nodal involvement, lymph node density ≥5.2%, ≥3 pathologically involved lymph nodes, and extranodal extension (ENE) were associated with worse RFS (all P < 0.05). On multivariate analysis, clinical N3 disease [adjusted hazard ratio (AHR)] 3.53, 95% confidence interval (CI) 1.68-7.45; P = 0.001), ≥3 pathologically involved lymph nodes (AHR 3.78, 95% CI 2.12-6.65; P < 0.001), and ENE (AHR 3.32, 95% CI 1.93-5.76; P < 0.001) were associated with worse RFS. The 3-year RFS for patients with cN0, cN1, cN2, and cN3 disease was 91.7%, 64.5%, 54.7%, and 38.3%, respectively. For men with ≥3 involved nodes, the 3-year RFS was 17% vs 82.4% in men with <3 involved nodes. The 3-year RFS was 29.7% in men with ENE and 85.7% in men without ENE., Conclusion: The presence of clinical N3 disease, ≥3 pathologically involved lymph nodes, and ENE was associated with worse RFS. As regional recurrence portends a dismal prognosis with few salvage options, adjuvant therapies should be developed for men with the aforementioned adverse factors., (© 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.)

Purpose: The benefit of adding androgen deprivation therapy (ADT) to dose-escalated radiation therapy (RT) for men with intermediate-risk prostate cancer is unclear; therefore, we assessed the impact of adding ADT to dose-escalated RT on freedom from failure (FFF)., Methods: Three groups of men treated with intensity modulated RT or 3-dimensional conformal RT (75.6-78 Gy) from 1993-2008 for prostate cancer were categorized as (1) 326 intermediate-risk patients treated with RT alone, (2) 218 intermediate-risk patients treated with RT and ≤6 months of ADT, and (3) 274 low-risk patients treated with definitive RT. Median follow-up was 58 months. Recursive partitioning analysis based on FFF using Gleason score (GS), T stage, and pretreatment PSA concentration was applied to the intermediate-risk patients treated with RT alone. The Kaplan-Meier method was used to estimate 5-year FFF., Results: Based on recursive partitioning analysis, intermediate-risk patients treated with RT alone were divided into 3 prognostic groups: (1) 188 favorable patients: GS 6, ≤T2b or GS 3+4, ≤T1c; (2) 71 marginal patients: GS 3+4, T2a-b; and (3) 68 unfavorable patients: GS 4+3 or T2c disease. Hazard ratios (HR) for recurrence in each group were 1.0, 2.1, and 4.6, respectively. When intermediate-risk patients treated with RT alone were compared to intermediate-risk patients treated with RT and ADT, the greatest benefit from ADT was seen for the unfavorable intermediate-risk patients (FFF, 74% vs 94%, respectively; P=.005). Favorable intermediate-risk patients had no significant benefit from the addition of ADT to RT (FFF, 94% vs 95%, respectively; P=.85), and FFF for favorable intermediate-risk patients treated with RT alone approached that of low-risk patients treated with RT alone (98%)., Conclusions: Patients with favorable intermediate-risk prostate cancer did not benefit from the addition of ADT to dose-escalated RT, and their FFF was nearly as good as patients with low-risk disease. In patients with GS 4+3 or T2c disease, the addition of ADT to dose-escalated RT did improve FFF., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: The purpose of this study was to evaluate the actuarial risk of local and regional failure in patients with completely resected non-small-cell lung cancer (NSCLC), and to assess surgical and pathological factors affecting this risk., Patients and Methods: Between January 1998 and December 2009, 1402 consecutive stage I-III (N0-N1) NSCLC patients underwent complete resection without adjuvant radiation therapy. The median follow-up was 42 months., Results: Local-regional recurrence was identified in 9% of patients, with local failure alone in 3% of patients, regional failure alone in 4% of patients, and both local and regional failure simultaneously in 2% of patients. Patients who had local failure were found to be at increased risk of mortality. By multivariate analyses, three variables were shown to be independently significant risk factors for local [surgical procedure (single/multiple wedges+segmentectomy versus lobectomy+bilobectomy+pneumonectomy), tumor size>2.7 cm, and visceral pleural invasion] and regional (pathologic N1 stage, visceral pleural invasion, and lymphovascular space invasion, LVI) recurrence, respectively., Conclusion: Patients with N0-N1 disease have low rates of locoregional recurrence after surgical resection. However, several prognostic factors can be identified that increase this risk and identify patients who may benefit from adjuvant treatment.

Background: During the first 3 years after prostate cancer treatment with radiation therapy, benign prostate-specific antigen (PSA) bounces are difficult for clinicians to distinguish from a biochemical recurrence, which can result in unnecessary interventions and erroneous predictions of outcomes. The objective of this study was to evaluate a commonly used PSA failure definition in a multinational, multi-institutional study after monotherapy with prostate brachytherapy., Methods: Participants were selected from 2919 men who underwent permanent prostate brachytherapy at the University Medical Center Utrecht, Princess Margaret Hospital, or Seattle Prostate Institute between 1998 and 2006. Inclusion required not having received androgen-deprivation therapy and having at least 30 months of follow-up. Failure was defined as any post-treatment use of hormone therapy, clinical relapse, or prostogram-defined biochemical (PSA) failure. Cases in which the nomogram predicted biochemical failure were evaluated at each institution to verify biochemical status over time and the actual clinical outcome at 5 years., Results: The median follow-up for the 1816 patients was 5.2 years. Concordance between the prostogram-predicted and actual outcomes, as measured by the Harrell c statistic, was 0.655 (95% confidence interval [CI], 0.536-0.774; P = .010) for the Princess Margaret group, 0.493 (95% CI, 0.259-0.648; P = .955) for the Seattle group, and 0.696 (95% CI, 0.648-0.744, P < .001) for the Utrecht group. The overall mean difference in biochemical recurrence-free survival at 5 years between actual outcomes and prostogram-defined outcomes was 9.2% (95% CI, 7.7%-10.6%). The total numbers of prostogram-defined and actual biochemical failures were 312 and 157, respectively (P = .001)., Conclusions: The widely used prostogram could not adequately distinguish a benign PSA bounce from a biochemical recurrence after prostate brachytherapy and could not be used to counsel patients about their predicted outcomes after treatment. The authors conclude that, to avoid unnecessary active interventions after treatment, clinicians should monitor PSA levels for at least 3 years and provide reassurance to patients that a PSA rise during this time is common and may not indicate a treatment failure., (Copyright © 2011 American Cancer Society.)

Purpose: Many clinicians use Prostogram data to advise patients selecting prostate cancer therapy. We examined whether the Prostogram accurately predicted recurrence at 5 years in patients treated with (125)I brachytherapy at 1 tertiary cancer center., Materials and Methods: We retrospectively reviewed the records of 208 consecutive patients with prostate cancer treated with a permanent (125)I implant without neoadjuvant androgen deprivation therapy at 1 tertiary cancer center during 1998 to 2006. In each patient the Prostogram brachytherapy formula was used to calculate 5-year biochemical recurrence-free survival probability based on clinical stage, Gleason sum score, prostate specific antigen and the receipt or not of external beam radiotherapy. Recurrence was defined as clinical relapse, death from disease, posttreatment androgen deprivation therapy, secondary treatments administered before prostate specific antigen failure or biochemical recurrence based on the Kattan modification of the American Society for Therapeutic Radiology and Oncology definition of biochemical recurrence after external beam radiation therapy. Patients were divided into quartiles based on Prostogram predicted 5-year recurrence-free survival probability and mean probability was compared to the actual 5-year recurrence-free survival rate in each quartile. Harrell's concordance statistic was used to assess the predictive accuracy of the nomogram., Results: Actual 5-year biochemical recurrence-free survival rates were superior to Prostogram predicted probabilities, including 89% vs 80%, 87% vs 86%, 100% vs 89% and 100% vs 94% in quartiles 1 to 4, respectively. Harrell's concordance value was 0.487 (95% CI 0.369-0.605), indicating that the predictive accuracy of the nomogram in our patients was less than 50%., Conclusions: The Prostogram did not predict recurrence after permanent prostate brachytherapy in this series. Institutional variability requires that clinicians be cautious when using the Prostogram to counsel patients about the probability of success after permanent prostate brachytherapy.

Objectives: To determine whether nadir prostate-specific antigen (PSA) levels within 12 months (nadir PSA12) after completion of radiotherapy (RT) can be used as an early marker of recurrence risk., Methods: A total of 4839 patients were treated with RT and without hormonal therapy from 1986 to 1995 for Stage T1-T2 prostate cancer at nine institutions. Of these 4839 patients, 4833, with a median follow-up of 6.3 years, met the criteria for analysis. The study endpoints included freedom from PSA failure, initiation of androgen deprivation, or documented local or distant failure (PSA-DFS); freedom from clinically apparent distant metastasis (DMFS); and overall survival (OS)., Results: Patients with a nadir PSA12 of 2.0 ng/mL or less had an 8-year PSA-DFS, DMFS, and OS rate of 55%, 95%, and 73%, respectively, compared with 40%, 88%, and 69%, respectively, for patients with a nadir PSA12 of more than 2.0 ng/mL. Multivariate analysis confirmed that a nadir PSA12 of greater than 2 ng/mL was an independent predictor of PSA-DFS, DMFS, and OS. Classification and regression tree analysis identified the nadir PSA12 levels after RT associated with PSA-DFS, DMFS, and OS. Nadir PSA12, combined with the pretreatment PSA level, identified patients at particularly high risk of distant metastasis., Conclusions: The results of this large, multi-institutional study have demonstrated that nadir PSA12 is predictive of clinical outcomes for patients with localized prostate cancer after RT. A high pretreatment PSA level and high nadir PSA12 will identify patients at particularly high risk who might benefit from early adjuvant therapy.

Objectives: To identify predictive factors for locoregional recurrence (LR), distant metastasis (DM), and overall survival (OS) in patients treated with chemoradiation and surgery for rectal cancer., Methods: Between 1989 and 2001, 470 patients with rectal cancer were treated with preoperative (89%) or postoperative (11%) chemoradiation and mesorectal excision. Median radiation dose was 45 Gy; 97% received concurrent infusional 5-fluorouracil, and 65% received adjuvant chemotherapy. Median follow-up interval was 5.7 years., Results: The 5-year rates of freedom from LR, freedom from DM, and OS were 90%, 79%, and 80%, respectively. On univariate analysis, significant predictors of LR were female sex, clinical T stage, pathologic T and N stages, and positive radial margin. Significant univariate predictors of DM were circumferential extent of tumor, tumor immobility, lymphovascular invasion, perineural involvement, and pathologic T and N stages. Significant univariate predictors of lower OS were age, circumferential extent of tumor, shorter distance from anal verge, tumor size, tumor immobility, anal canal involvement, lymphovascular invasion, perineural involvement, positive radial margin, and pathologic T and N stages. On Cox multivariate analysis, female sex and pathologic T and N stages independently predicted for LR; pathologic T and N stages independently predicted for DM; and age, circumferential extent of tumor, positive radial margin, and pathologic T and N stages independently predicted for lower OS., Conclusions: Pathologic T and N stages significantly predicted for all 3 end points (LR, DM and OS) on multivariate analysis. Investigations of more aggressive adjuvant chemotherapy appear warranted for pathologic stage T3/T4 or N1/2 rectal cancer.

Purpose: To determine the clinical variables associated with inadequate salvage cryotherapy and to correlate the disease-free survival rates associated with biopsy results in prostate cancer (CaP)., Methods and Materials: Between July 1992 and January 1995, 150 patients underwent salvage cryotherapy for locally recurrent CaP. Biopsy specimens were examined for the presence of cancer cells and normal or atypical glands, all of which were considered evidence of inadequate cryotherapy. Clinical variables, as predictors of biopsy results, were evaluated with univariate and multivariate analyses. The impact of the biopsy results on disease-free survival was also determined., Results: The number of cryoprobes and freeze-thaw cycles correlated with inadequate cryotherapy (p = 0.037 and p = 0.0022, respectively). The number of freeze-thaw cycles was an independent predictor of inadequate cryotherapy (p = 0.003). The finding of cancer cells in the biopsy specimens was the only histopathologic variable that affected disease-free survival (p = 0.016)., Conclusion: Complete ablation of the prostate gland and tumor is difficult to achieve with salvage cryotherapy. To optimize for complete ablation, salvage cryotherapy should include at least two freeze-thaw cycles and a minimum of five cryoprobes. The finding of atypical or normal epithelial tissue in biopsy specimens after salvage cryotherapy is not predictive of biochemical failure.

Purpose: We set out to determine whether patients who underwent prostatectomy for recurrence after external-beam radiotherapy for prostate cancer had a higher incidence of alterations in the apoptotic pathway than did patients who underwent surgery as initial treatment., Materials and Methods: Twenty patients who underwent unsuccessful full-dose external-beam radiotherapy for prostate cancer and subsequently underwent salvage radical surgery (radio-recurrent group), and 20 patients matched for various clinical parameters who underwent only radical prostatectomy for localized or locally advanced prostate cancer (radio-naive group), were studied. Tissue samples were examined for immunoreactivity for p53, p21, Bcl-2, and Ki-67 proteins. Statistically, the two groups were compared using exact logistic regression., Results: Fifty-five percent of the tumors from patients initially treated with radiotherapy were noted to overexpress Bcl-2; whereas, in the radio-naive group, no patient had Bcl-2 overexpression (p = 0.0004). More patients who underwent salvage radical surgery were found to have a higher mean proliferative index (Ki-67 staining) (39.6%), compared with patients undergoing prostatectomy alone (22.1%), p = 0.0800. No significant difference was noted in immunohistochemical expression of p53 and p21 between the two groups., Conclusions: Patients undergoing radical prostatectomy after radiotherapy had a significantly higher rate of Bcl-2 overexpression than did patients who underwent surgery as the initial treatment. Alterations in the apoptotic pathway may be important in the development of local recurrence after radiation therapy.

Purpose: We determined the biochemical failure rate in patients 60 years and younger, and older than 60 years old who were treated with external beam radiation for localized prostate cancer or locally advanced prostate cancer. We also evaluated prognostic factors in the 2 age groups., Materials and Methods: We reviewed the medical records of 964 patients who received full dose radiotherapy as the only treatment for prostate cancer. Followup prostate specific antigen was measured 3 to 6 months after the completion of radiotherapy and every 3 to 6 months thereafter. Biochemical failure was defined using the criteria established by the American Society for Therapeutic Radiology and Oncology Consensus Panel. Median followup in the whole study group was 48 months., Results: Of the 98 men 60 years or younger 46 (47%) had biochemical failure, whereas 261 (30%) of the 866 older than 60 years old had biochemical failure. The 5 and 7-year biochemical disease-free survival rates were 55% and 47% in the younger men, and 65% and 59% in the older men, respectively. These rates were significantly lower in the younger men (p = 0.017 and 0.027, respectively). Multivariate regression showed that in men 60 years or younger initial prostate specific antigen, Gleason score and lower radiation doses were predictive of biochemical failure., Conclusions: Men with prostate cancer who are 60 years or younger and treated with radiotherapy may be at significant risk for long-term biochemical failure.

The purpose of this study was to review the clinical course of patients diagnosed with vulvar melanoma. Charts of patients diagnosed between 1970 and 1997 were reviewed for demographics, lesion characteristics, disease duration and extent, and treatments. Actuarial survival curves were computed by the Kaplan Meier method and compared by Cox proportional hazards regressions. Fifty-one patients (median age 54) with vulvar melanoma presented with a vulvar mass (39%), pain (30%), bleeding (24%), and itching (20%). Anatomical distribution was mucosa of the vulva (65%), vulvar epidermal site (21%), or unspecified vulva (14%), with 20% having multifocal disease at diagnosis. Histologic types were superficial spreading or nodular (50% each). Median lesion characteristics were diameter 2 cm, Breslow index 4.4 mm, and Clark level IV. Distribution of patients per American Joint Committee on Cancer (AJCC) stage was 29%, 50%, 16%, and 7% for stages I, II, III and IV, respectively. Inguinal node metastases were unilateral in 16% and bilateral in 7%. Despite complete surgical resection, 32 patients (63%) recurred. Median survival for all patients was 41 months (range, 5-324), with 91% 5-year survival for patients with stage I and 31% for stage >or= IIA (P = 0.0002). As with cutaneous melanoma, the AJCC classification, Breslow's thickness, and Clark's levels are the major predictors of overall survival (P = 0.0001 each) and disease-free survival (P