Stage T2 Disease Research Articles

Primary Cutaneous B-Cell Lymphomas: Recent Advances in Diagnosis and Management

Primary cutaneous B-cell lymphoma (PCBCL) is a heterogeneous group of rare clonal B-cell lymphoproliferative disorders with distinct clinicopathologic features from more common nodal B-cell lymphomas. We performed a systematic review of the relevant literature in the MEDLINE database and analyzed laboratory and clinical data. This review discusses the three most common types of PCBCL: primary cutaneous marginal zone lymphoma (PCMZL), primary cutaneous follicle-center lymphoma (PCFCL), and primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL, LT). Skin biopsies with histology, immunohistochemistry, and molecular clonality studies are essential for a correct diagnosis of cutaneous B-cell lymphoma. Comprehensive lymphoma staging with laboratory and imaging studies and bone marrow aspiration and biopsy are important for determining the prognosis and differentiation of PCBCL from secondary skin involvement with systemic B-cell lymphomas. PCMZL and PCFCL are low-grade PCBCLs, with an estimated 5-year disease-specific survival rate of greater than 95%. Surgical excision or focal radiation therapy is sufficient to control stages T1 and T2 disease. Rituximab monotherapy is frequently used for patients with stage T3 disease. PCDLBCL, LT is an intermediate-grade B-cell lymphoma, with a 5-year disease-specific survival rate of approximately 50%. An anthracycline-based chemotherapy regimen with rituximab is usually required as initial therapy to improve outcomes. In less than a decade, significant progress has been made in our understanding of PCBCL. Novel classification, staging, and prognostic systems have resulted in more accurate diagnosis and prognosis. Although no randomized prospective studies have been conducted in PCBCL, therapies derived from systemic B-cell lymphomas have shown promising results.

Performance Characteristics of Prostate-specific Antigen in Patients Undergoing Radical Prostatectomy

To assess the performance characteristics of prostate-specific antigen (PSA) for predicting the volume of total or high-grade cancer in men undergoing radical prostatectomy. It is known that the performance characteristics of PSA are improved for predicting the presence of high-grade prostate cancer. We identified 1459 patients from the Stanford Radical Prostatectomy Database with clinical Stage T1c (n = 783) and T2 (n = 676) disease who underwent surgery from 1988 to 2003 with detailed morphometric mapping. We generated receiver operating characteristic curves for PSA levels according to the total and high-grade (Gleason score 4 or 5) cancer volume and compared the areas under the curve (AUC) for the various total and high-grade cancer volumes. For patients with Stage T1c disease, the AUC for the PSA ROC curve increased in a stepwise fashion as both the total cancer volume and the high-grade cancer volume increased. Significant differences between the AUCs for low and high volumes of total and high-grade disease were observed. For T2 disease, the AUCs for predicting high-grade cancer volume were generally greater than the corresponding AUCs for T1c disease, although no incremental increase was observed. In patients with Stage T1c disease, in whom the PSA level was the driving force for biopsy, the PSA performance improved in a stepwise fashion with greater total and high-grade cancer volumes as evidenced by improved ROC. Previous studies have shown that PSA performs better for detecting the presence of high-grade disease. We have shown that PSA performs better in predicting greater volumes of high-grade disease in radical prostatectomy specimens.

1340 PROTOCOL-BASED REASONS TO SWITCH TO RADICAL PROSTATECTOMY AFTER INITIAL ACTIVE SURVEILLANCE PREDICT FOR UNFAVOURABLE OUTCOME

You have accessJournal of UrologyProstate Cancer: Localized VI1 Apr 20121340 PROTOCOL-BASED REASONS TO SWITCH TO RADICAL PROSTATECTOMY AFTER INITIAL ACTIVE SURVEILLANCE PREDICT FOR UNFAVOURABLE OUTCOME Meelan Bul, Xiaoye Zhu, Chris Bangma, and Monique Roobol Meelan BulMeelan Bul Rotterdam, Netherlands More articles by this author , Xiaoye ZhuXiaoye Zhu Rotterdam, Netherlands More articles by this author , Chris BangmaChris Bangma Rotterdam, Netherlands More articles by this author , and Monique RoobolMonique Roobol Rotterdam, Netherlands More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.1722AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Little is known about the outcome of the radical prostatectomy (RP) specimens of men initially followed using active surveillance (AS) for low-risk prostate cancer (PC). We evaluated the association between the reason to switch to RP and RP outcome in our prospective AS cohort. METHODS Eligible men were initially diagnosed with low-risk PC (clinical stage =<T2, PSA =<10 ng/ml, PSA density <0.2 ng/ml/ml, 1 or 2 positive biopsy cores and Gleason score [GS] =<6) and underwent RP between December 2006 and July 2011. The study protocol recommends active treatment in case of risk reclassification on repeat biopsy after 1 yr (Gleason score >6 and/or >2 positive cores) or a PSA doubling-time =<3 yrs. Reasons to undergo active treatment in the form of RP and pathology findings on T stage and Gleason grade were studied. Unfavourable disease on RP was defined as T3-4 and/or GS >=4+3. RESULTS A total of 413 men switched to active therapy of which 189 men (46%) opted for RP. Pathology results were available in 167 men (88.4%). Median time to RP was 1.3 yrs (25-75p: 1.1-1.8 yrs). Protocol-based recommendations led to deferred RP in 128 (77%) men; 17 (10%) switched due to anxiety and 22 (13%) had other reasons (e.g. PSA increase). Pathology results showed T3 and T4 stage disease in 30 (18%) and 2 (1%) cases respectively. A GS of 4+3 was found in 21 cases (13%), while 3 (2%) had a GS of 8. The table shows the number of men with protocol-based reasons to switch to deferred treatment associated with either favourable or unfavourable RP results. In patients in whom anxiety triggered the choice for RP only 1 out of 17 (6%) had an unfavourable outcome. Number of men with protocol-based reasons to switch to deferred treatment with either favourable or unfavourable radical prostatectomy results N Favourable RP outcome (N = 118), (pT2 and GS =<3+4) Unfavourable RP outcome (N = 49), (pT3-4 and/or GS >=4+3) Protocol-based reason to switch to deferred treatment⁎ N (%) N (%) Any protocol-based reason 128 88(69) 40(31) 1.) GS >= 7 on repeat biopsy 23 18(78) 5(22) 2.) >= 3 positive cores on repeat biopsy 35 27(77) 8(23) 3.) PSA-DT =< 3yrs⁎⁎ 24 17(71) 7(29) Combination 1 + 2 21 10(48) 11(52) Combination 1 + 3 4 2(50) 2(50) Combination 2 + 3 17 12(71) 5(29) Combination 1 + 2 + 3 4 2(50) 2(50) N; number of patients, RP; radical prostatectomy, pT; pathological T stage, GS; Gleason score, ⁎ ; includes patients with the particular protocol-based reason in the absence of any other reason, PSA-DT; prostate-specific antigen doubling time, ⁎⁎ ; PSA-DT was used for recommendations only after a minimum of 4 follow-up visits CONCLUSIONS The majority of men in our cohort had a protocol-based reason to switch to deferred RP of whom a relatively high percentage had an unfavourable RP result when compared to men undergoing RP with no other reason than anxiety. Since risk reclassification during AS follow-up is common and often occurs within 1-2 yrs of diagnosis, it is important to improve selection of low-risk PC patients by adequate biopsy sampling at study entry and with regular repeat biopsies during follow-up, in order to prevent withholding curative treatment in patients at higher risk. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e543-e544 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Meelan Bul Rotterdam, Netherlands More articles by this author Xiaoye Zhu Rotterdam, Netherlands More articles by this author Chris Bangma Rotterdam, Netherlands More articles by this author Monique Roobol Rotterdam, Netherlands More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Performance characteristics of PSA in patients undergoing radical prostatectomy.

199 Background: The Prostate Cancer Prevention Trial demonstrated that the performance characteristics of PSA are improved for diagnosis of high grade disease. We assessed the performance of PSA for determining total and high grade cancer volume in a radical prostatectomy series. Methods: We identified 1307 patients from the Stanford Radical Prostatectomy Database with clinical stage T1c (n=658) and T2 (n=549) disease who had surgery between 1988 and 2002 and detailed morphometric mapping by a single pathologist. Patients with T1c and T2 disease were analyzed separately as the indication for biopsy was different in these two populations (elevated PSA versus abnormal DRE). We generated receiver operating characteristic (ROC) curves for PSA based on total tumor volume and volume of Gleason 4 or 5 disease and compared the areas under the curve (AUC) for different cut points of total and high grade cancer volume. Results: For patients with clinical stage T1c disease, as total and high grade cancer volumes increased, so did the AUC for PSA performance. There was a significant difference in AUC for PSA for total cancer volumes greater than 0.5 cc (AUC=0.62) compared to greater than 2 cc (AUC=0.72, p=0.02), and also between volumes greater than 2 cc (AUC=0.72) and 5 cc (AUC=0.79, p=0.0003, Fig.1). The AUC for PSA performance for volume of high grade disease increased from 0.66, to 0.68, to 0.76 for Gleason 4 or 5 volumes of 0, 0.5, and 3 cc, respectively (Fig. 2). For patients with clinical stage T2 disease, the AUCs for total or high grade cancer volume were not different across cut points, but were overall higher compared to the T1c group. Conclusions: In T1c patients, PSA performance improved in a stepwise fashion with higher total and high grade cancer volumes as evidenced by improved receiver operating characteristics. In T2 patients, no similar trend was observed, although overall PSA performance was improved compared to T1c patients. Prior studies show that PSA performs better for the detection of high grade disease; here, we show that PSA performs better in predicting volume of high grade disease in radical prostatectomy specimens.

Identifying Better Practices for Early-stage Bladder Cancer

Practice guidelines for nonmuscle invasive (ie, early stage) bladder cancer are ambiguous, resulting in substantial practice variation without a clear patient benefit. To profile urologist practice styles and empirically derive better patterns of use for common bladder cancer services. Retrospective cohort. Elderly patients diagnosed with early-stage bladder cancer between January 1, 1992 and December 31, 2005 in Surveillance, Epidemiology, and End Results-Medicare linked data. After identifying each patient's treating urologist, we fit multilevel models to obtain reliability-adjusted measures of the urologist's use of surveillance-associated (cytoscopy and urine cytology) and treatment-associated (intravesical therapy) services during the 2 years after diagnosis. We then used the Cox proportional hazards regression to evaluate the association between a patient's risk of bladder cancer death and his urologist's frequency of service use. Regardless of disease severity, no measurable patient benefit was associated with care delivery by a urologist residing in the highest quartile for cystoscopy or intravescial therapy use. However, maximal intensity of cytology use was associated with a lower risk of bladder cancer death for patients with high-grade stage Ta/Tis (highest vs. lowest intensity quartiles: hazard ratio, 0.73; 95% confidence interval, 0.56-0.95) and stage T1 disease (hazard ratio, 0.59; 95% confidence interval, 0.49-0.72). Our analysis supports a more tailored approach to patients with early-stage bladder cancer. Further, it serves as an example for applying observational data to characterize better clinical practices in the absence of experimental studies.

Locally advanced prostate cancer: a population‐based study of treatment patterns

Study Type--Therapy (practice patterns). Level of Evidence 2b. What's known on the subject? And what does the study add? The treatment of locally advanced prostate cancer varies widely even though there is level one evidence supporting the use of multimodality therapy as compared with monotherapy. This study defines treatment patterns of locally advanced prostate cancer within the United States and identifies predicators of who receives multimodality therapy rather than monotherapy. • To identify treatment patterns and predictors of receiving multimodality therapy in patients with locally advanced prostate cancer (LAPC). • The cohort comprised patients ≥66 years with clinical stage T3 or T4 non-metastatic prostate cancer diagnosed between 1998 and 2005 identified from the Surveillance, Epidemiology and End Results (SEER) cancer registry records linked with Medicare claims. • Treatments were classified as radical prostatectomy (RP), radiation therapy (RT) and androgen deprivation therapy (ADT) received within 6 and 24 months of diagnosis. • We assessed trends over time and used multivariable logistic regression to identify predictors of multimodality treatment. • Within the first 6 months of diagnosis, 1060 of 3095 patients (34%) were treated with a combination of RT and ADT, 1486 (48%) received monotherapy (RT alone, ADT alone or RP alone), and 461 (15%) received no active treatment. • The proportion of patients who received RP increased, exceeding 10% in 2005. • Use of combined RT and ADT and use of ADT alone fluctuated throughout the study period. • In all 6% of patients received RT alone in 2005. • Multimodality therapy was less common in patients who were older, African American, unmarried, who lived in the south, and who had co-morbidities or stage T4 disease. • Treatment of LAPC varies widely, and treatment patterns shifted during the study period. • The slightly increased use of multimodality therapy since 2003 is encouraging, but further work is needed to increase combination therapy in appropriate patients and to define the role of RP.

Quality of Life After Hypofractionated Concomitant Intensity-Modulated Radiotherapy Boost for High-Risk Prostate Cancer

To evaluate the change in health-related quality of life (QOL) of patients with high-risk prostate cancer treated using hypofractionated radiotherapy combined with long-term androgen deprivation therapy. A prospective Phase I-II study enrolled patients with any of the following: clinical Stage T3 disease, prostate-specific antigen level ≥20 ng/mL, or Gleason score 8-10. Radiotherapy consisted of 45 Gy (1.8 Gy per fraction) to the pelvic lymph nodes with a concomitant 22.5 Gy intensity-modulated radiotherapy boost to the prostate, for a total of 67.5 Gy (2.7 Gy per fraction) in 25 fractions over 5 weeks. Daily image guidance was performed using three gold seed fiducials. Quality of life was measured using the Expanded Prostate Cancer Index Composite (EPIC), a validated tool that assesses four primary domains (urinary, bowel, sexual, and hormonal). From 2004 to 2007, 97 patients were treated. Median follow-up was 39 months. Compared with baseline, at 24 months there was no statistically significant change in the mean urinary domain score (p = 0.99), whereas there were decreases in the bowel (p < 0.01), sexual (p < 0.01), and hormonal (p < 0.01) domains. The proportion of patients reporting a clinically significant difference in EPIC urinary, bowel, sexual, and hormonal scores at 24 months was 27%, 31%, 55%, and 60%, respectively. However, moderate and severe distress related to these symptoms was minimal, with increases of only 3% and 5% in the urinary and bowel domains, respectively. Hypofractionated radiotherapy combined with long-term androgen deprivation therapy was well tolerated. Although there were modest rates of clinically significant patient-reported urinary and bowel toxicity, most of this caused only mild distress, and moderate and severe effects on QOL were limited. Additional follow-up is ongoing to characterize long-term QOL.

External-beam radiation therapy should be given with androgen deprivation treatment for intermediate-risk prostate cancer: new confirmatory evidence

External-beam radiation therapy should be given with androgen deprivation treatment for intermediate-risk prostate cancer: new confirmatory evidence

The Long-Term Outcomes after Radical Prostatectomy of Patients with Pathologic Gleason 8–10 Disease

Background. We explored the long-term clinical outcomes including metastases-free survival and prostate cancer-specific survival (PCSS) in patients with pathologic Gleason 8–10 disease after radical prostatectomy (RP). Methods. We report on 91 patients with PCSS data with a median followup of 8.2 years after RP performed between 1988 and 1997. Cox regression and Kaplan-Meier analysis were used to evaluate year of surgery, pathologic stage, and surgical margin status as predictors of PCSM. Results. Median age was 65 years (IQR: 61–9), and median PSA was 9.7 ng/ml (IQR: 6.1–13.4). Of all patients, 62 (68.9%) had stage T3 disease or higher, and 48 (52.7%) had a positive surgical margin. On multivariate analysis, none of the predictors were statistically significant. Of all patients, the predicted 10-year BCR-free survival, mets-free survival, and PCSS were 59% (CI: 53%–65%), 88% (CI: 84%–92%), and 94% (CI: 91%–97%), respectively. Conclusions. We have demonstrated that cancer control is durable even 10 years after RP in those with pathologic Gleason 8–10 disease. Although 40% will succumb to BCR, only 6% of patients died of their disease. These results support the use of RP for patients with high-risk localized prostate cancer.

Prognostic significance of breast cancer subtype and p53 overexpression in patients with locally advanced or high-risk breast cancer treated using upfront modified radical mastectomy with or without post-mastectomy radiation therapy

Although post-mastectomy radiation therapy (PMRT) has shown benefits, its effects in patient subpopulations remain uncertain. Therefore, we assessed whether breast cancer subtype and p53 overexpression were associated with outcome after modified radical mastectomy (MRM), with or without PMRT. We retrospectively analyzed the records of patients who underwent MRM, with or without PMRT, between January 1991 and December 2008. Patients were considered eligible if they had T3 or T4 stage disease; any T stage with N2 or N3 stage; any T or N stage with positive, close (<1 mm) resection margins; or skin, nipple, or pectoral muscle invasion. We used immunohistochemistry and/or fluorescent in situ hybridization to determine breast cancer subtypes and p53 overexpression status. We found that 104 patients were eligible, including 59 (56.7%) who underwent PMRT and 45 (43.3%) who did not. Median follow-up duration was 61.3 months (range 16.1-232.7). Overall survival (OS) was significantly longer in patients who underwent PMRT (P = 0.029). This trend was evident in the subgroup of luminal type A breast cancer (P = 0.017) and non-p53 overexpression (P = 0.026) patients. However, there was no significant survival benefit from PMRT in the subgroup of triple negative (TN) breast cancer (P = 0.528) and p53 overexpression (P = 0.189) patients. The benefit of PMRT differed among subgroups with different breast cancer subtype and p53 overexpression. More efficacious systemic treatment strategies are needed, especially in patients at high risk for distant metastasis, to obtain optimal therapeutic gain.

Surgical margin status among men with organ-confined (pT2) prostate cancer: a population-based study

: Following prostate cancer surgery, positive surgical margin (PSM) status varies among institutions and there is evidence that high-volume surgeons and centres obtain better oncological results. However, larger studies recording PSM for radical prostatectomy (RP) are from large "centres of excellence" and not population-based. Cancer Care Ontario undertook an audit of pathology reports to determine the province-wide PSM rate for pathological stage T2 (pT2) disease prostate cancer and to assess the overall and regional-based PSM rates based on surgical volume to understand gaps in quality of care prior to undertaking quality improvement initiatives. : Data were extracted as part of the Pathology Project Audit data output (2005, 2006). Pathology reports were submitted to Cancer Care Ontario by Ontario hospitals electronically via the Pathology Information Management System. An experienced cancer pathology coder extracted the PSM data from eligible RP cancer specimen pathology reports. Only reports that provided a pathological stage were included in the analysis. Biopsy and transurethral resection of the prostate reports were excluded. A convenience sample of 1346 reports from 2006 and 728 from 2005 were analyzed. Regression analysis was performed to assess volume-margin associations. : The median province-wide surgical PSM rate for pT2 disease was 33%, ranging 0-100% among 43 hospitals where RP volumes ranged 12-625. There was no significant correlation (p > 0.05) between volume and PSM by logistic regression with variable odds ratios (95% confidence interval [CI]) for PSM by quartile (1(st) = 1.66 [0.93-2.96]; 2(nd) = 0.97 [0.58-1.62]; 3(rd) = 1.44[0.91-2.29]) compared to the highest volume last quartile. Mean PSM rates between community and teaching hospitals were not significantly different. : The province-wide PSM rate for pT2 disease prostate cancer undergoing RP is higher than those published from "centres of excellence." Results from larger volume centres were not statistically significantly better, which contradicts previously published data. Factors, such as individual surgeon, patient selection, pathological processing and interpretation, may explain the differences.

High incidence of asymptomatic renal cancer in late survivors after heart transplantation

advised. 1 There are no current guidelines for the screening of other cancers. We report 5 patients with asymptomatic renal cancer discovered among our HTR cohort. First, incidental renal cancers were found between 2006 and 2009 in 2 patients who underwent abdominal computed tomography for other purposes (Patients 1 and 2, Table 1). This led us to perform routine abdominal ultrasound imaging in all our HTRs at more than 3 years after transplant, from October 2009 to October 2010. Of 96 patients, 93 provided informed consent and underwent screening. Median time after transplantation was 12 years (range, 4 –25 years). Fifty-five patients had a history of smoking, 78 had hypertension, 8 required renal dialysis, and 43 had a creatinine clearance 60 ml/min, without dialysis. Among these 93 patients, we found renal cancer in 3 additional patients and 2 patients with an atypical renal cyst that required follow-up. The renal tumor was ablated in 5 patients and was found to be clear cell carcinoma in 2, papillary in 2, and chromophobe cell in 1 (Table 1). All were T1 stage disease. Time to transplant was 15 years or more in 4 of these patients. One of the patients with renal cancer died 10 months later from a primary lung cancer. None had renal cancer relapse, with a follow-up ranging from 8 months to 4 years. This prevalence of asymptomatic renal cancer in HTR is far higher than expected in the general population. For instance, across Europe, the incidence of renal carcinoma among men ranges from 2.09/100,000 to 15.2/100,000. 2 The relative incidence of malignancy as a cause of death in patients surviving more than 10 years was 27% in our cohort (9 of 33 deaths), an incidence not statistically different from that previously reported in International Society for Heart and Lung Transplantation registry (23% of 3952 deaths, p 0.7). 3 We think that the high prevalence of renal cancer in these patients is best explained by a long mean time from transplant resulting in prolonged exposure to usual risk factors of renal cancer such as immunosuppressive therapy, hypertension, and renal failure. 2 Finally, our study suggests that routine abdominal echography for renal cancer screening could be useful in the very long-term care of these patients. However, we need to demonstrate that the benefits of this screening outweigh harm. First, echography may result in cancer over-diagnosis if the tumor growth is too slow to cause symptoms before the patient dies of another cause. 4,5 Second, this screening may lead to unnecessary and dangerous surgical interventions or biopsies. 4 Indeed, renal biopsy resulted in a hematoma in 1 patient of our series without carcinoma, prolonging hospitalization. Thus, further studies are needed to determine more accurately define the benefit/risk ratio of such screening.

Effect of Age on Transitional Cell Carcinoma of the Upper Urinary Tract: Presentation, Treatment, and Outcomes

To determine the effect of age on the disease characteristics, treatment administered, and disease-specific survival (DSS) for patients with upper tract urothelial carcinoma. The effect of advancing age on the disease extent and survival has not been well delineated in patients with upper tract urothelial carcinoma. Using the Surveillance, Epidemiology, and End Results database from the National Cancer Institute, we identified patients diagnosed with UTUC from 1984 to 2004. The data were analyzed for age (40-49, 50-59, 60-69, 70-79, and ≥80 years), sex, race, disease extent, treatment type, and cause of death. Relationships among age, clinicopathologic features, and treatment were tabulated. The effect of age on overall and DSS were calculated using Cox proportional hazards ratio analyses. The final cohort consisted of 12 639 patients. Advancing age was associated with greater T stage and grade at presentation. Of those 40-49 years old, 41% presented with invasive tumors (T2-T4) compared with 50% of octogenarians. Poor or undifferentiated tumors increased in frequency from 42% among those 40-49 years old to 59% among those≥80 years old. Extirpative surgery was less likely among those with Stage T1 or less disease (88.3% vs 92.8%). Octogenarians were less likely to have undergone extirpative surgery than those 40-49 years old (86% vs 95%). Despite adjustments for T stage, grade, and treatment, DSS (hazard ratio 2.64) worsened with increasing age. With advancing age, we found a corresponding increase in stage and grade at presentation. After adjustment for stage, grade, and treatment type, older patients still had worse DSS.

Small Prostate Size and High Grade Disease—Biology or Artifact?

Prior radical prostatectomy series have shown an inverse association between prostate size and high grade cancer. It has been suggested that smaller size prostates arise in a low androgen environment, enabling development of more aggressive cancer. We propose that this observation is the result of ascertainment bias driven by prostate specific antigen performance. We identified 1,404 patients from the Stanford Radical Prostatectomy Database with clinical stage T1c (723) and T2 (681) disease who underwent surgery between 1988 and 2002, and underwent detailed morphometric mapping by a single pathologist. Multivariate linear regression was performed to assess for the effects of age, prostate weight and prostate specific antigen on total and high grade (Gleason grade 4/5) cancer volume and percentage of high grade disease. In patients who underwent biopsy due to abnormal prostate specific antigen (stage T1c), prostate weight was negatively associated (p = 0.0002) with total cancer volume, volume of high grade disease and percentage of high grade disease. For patients who underwent biopsy based on abnormal digital rectal examination (stage T2) these associations were not observed. Improved prostate specific antigen performance for high grade disease results in ascertainment bias in patients with T1c disease. Thus, the association between prostate size and high grade disease may be a consequence of grade dependent performance of prostate specific antigen rather than true tumor biology.

1468 INTRAFASCIAL BILATERAL NERVE SPARING RADICAL PROSTATECTOMY: DOES THE ROBOTIC-ASSISTED APPROACH PREDISPOSE TO HIGHER RISK OF POSITIVE SURGICAL MARGINS? IMPORTANCE OF PATIENT SELECTION

You have accessJournal of UrologyProstate Cancer: Localized1 Apr 20111468 INTRAFASCIAL BILATERAL NERVE SPARING RADICAL PROSTATECTOMY: DOES THE ROBOTIC-ASSISTED APPROACH PREDISPOSE TO HIGHER RISK OF POSITIVE SURGICAL MARGINS? IMPORTANCE OF PATIENT SELECTION Nazareno Suardi, Andrea Gallina, Niccolò Buffi, Emanuele Scapaticci, Matteo Zanoni, Giulio Gadda, Giovanni Lughezzani, Aldo Bocciardi, Luciano Nava, Alberto Briganti, Andrea Cestari, Patrizio Rigatti, Giorgio Guazzoni, and Francesco Montorsi Nazareno SuardiNazareno Suardi milan, Italy More articles by this author , Andrea GallinaAndrea Gallina milan, Italy More articles by this author , Niccolò BuffiNiccolò Buffi milan, Italy More articles by this author , Emanuele ScapaticciEmanuele Scapaticci milan, Italy More articles by this author , Matteo ZanoniMatteo Zanoni milan, Italy More articles by this author , Giulio GaddaGiulio Gadda milan, Italy More articles by this author , Giovanni LughezzaniGiovanni Lughezzani milan, Italy More articles by this author , Aldo BocciardiAldo Bocciardi milan, Italy More articles by this author , Luciano NavaLuciano Nava milan, Italy More articles by this author , Alberto BrigantiAlberto Briganti milan, Italy More articles by this author , Andrea CestariAndrea Cestari milan, Italy More articles by this author , Patrizio RigattiPatrizio Rigatti milan, Italy More articles by this author , Giorgio GuazzoniGiorgio Guazzoni milan, Italy More articles by this author , and Francesco MontorsiFrancesco Montorsi milan, Italy More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.1403AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The effect of the type of intrafascial approach (open vs robotic assisted) on the rate of positive surgical margins (PSM) has not been addressed yet. We hypothesized that RA intrafascial BNSRP might be associated with a higher risk of PSM due to a surgical dissection plane potentially closer to the prostatic capsule. METHODS Between 2004 and 2009, 501 consecutive patients underwent either open or RA intrafascial BNSRP for clinically localized PCa. Exclusion criteria for intrafascial approach were: clinical stage T3 disease, PSA>20 ng/ml or biopsy Gleason sum (GS) ≥8. Patients were stratified according to surgical approach (open vs RA). Uni and multivariable logistic regression models tested the association between surgical approach and the risk of positive surgical margins (PSM), after adjusting for PSA, biopsy GS, clinical stage and % of positive cores. The same analyses were repeated in patients with pre-operative very low-risk patients (PSA<10 ng/ml, clinical stage T1, biopsy GS≤ 6 and % positive cores ≤33%). RESULTS 293 (58.5%) and 208 (41.5%) patients were treated with open RP and RA BNSRP, respectively. Patients treated with RALP were younger (mean age: 60.1 vs. 63.5 yrs, p<0.001) and had lower PSA (6.1 vs. 7.1, p=0.008). Clinical stage (T2 in 34.6% vs. 16.7%;p<0.001) and Biopsy GS(7 in 28.6% vs. 7.7%) were higher in the open group (p<0.001). Patients in RALP group had significantly lower % of positive cores (35.7% vs. 28.4% respectively, p=0.02). The rate of PSM was higher in patients submitted to RA BNSRP in the overall population (22.1% vs. 12.5% respectively, p=0.005) as well as in patients with pathologically organ-confined disease (20.0 vs. 9.4%, respectively, p=0.02). At multivariable analyses, the surgical approach independently associated with PSM (p=0.01). Patients treated with RALP had a 2.8 fold increased risk of PSM as compared to open. However, when only patients with very low-risk disease were considered (n=84), patients treated with RALP had the same rate of PSM as compared to open(8.7 vs. 2.6% respectively, p=0.2). In this category, the surgical approach was not associated with a higher risk of PSM (p=0.3). CONCLUSIONS We demonstrated that patients treated with RA intrafascial BNSRP the has an higher risk of PSM. However, in patients with very low-risk disease open and RALP intrafascial BNSRP achieve the same PSM rates. Therefore, only highly selected patients (PSA<10 ng/ml, clinical stage T1, biopsy GS≤ 6 and 33% positive cores) should be candidated to intrafascial RA BNSRP. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e588 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Nazareno Suardi milan, Italy More articles by this author Andrea Gallina milan, Italy More articles by this author Niccolò Buffi milan, Italy More articles by this author Emanuele Scapaticci milan, Italy More articles by this author Matteo Zanoni milan, Italy More articles by this author Giulio Gadda milan, Italy More articles by this author Giovanni Lughezzani milan, Italy More articles by this author Aldo Bocciardi milan, Italy More articles by this author Luciano Nava milan, Italy More articles by this author Alberto Briganti milan, Italy More articles by this author Andrea Cestari milan, Italy More articles by this author Patrizio Rigatti milan, Italy More articles by this author Giorgio Guazzoni milan, Italy More articles by this author Francesco Montorsi milan, Italy More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...

The impact of comorbidity on survival among men with localized prostate cancer.

8 Background: To provide patients and clinicians more accurate estimates of co-morbidity specific survival stratified by patient age, tumor stage and tumor grade. Methods: We conducted a ten year competing risk analysis of 19,639 men age 66 years and older identified by the Surveillance, Epidemiology and End Results (SEER) program linked to Medicare program files. All men were diagnosed with localized prostate cancer and received no surgery or radiation within 180 days of diagnosis. The analysis was stratified by tumor grade and stage and by age and co-morbidity at diagnosis classified using the Charlson co-morbidity index. Underlying causes of death were obtained from SEER. Results: During the first ten years following diagnosis men with moderately and poorly differentiated prostate cancer were more likely to die from causes other than their disease. For men age 66-74 years with stage T1c Gleason score 5-7 disease at diagnosis, ten year overall mortality rates and prostate cancer specific rates were 28.8%, 50.5%, 83.1% and 4.8%, 2.0%, 5.3% respectively for men with Charlson scores 0, 1 and &gt; 2. For men age 66-74 years with T1c Gleason score 8-10 disease at diagnosis, the corresponding rates were 55.0%, 52.0%, 64.3% and 25.7%, 20.2%, 13.7% respectively for men with Charlson scores 0, 1, &gt; 2. Death from competing medical hazards was roughly comparable for men with stage T2 disease and higher for all men over age 75. Conclusions: Patients and clinicians should consider using co-morbidity specific data to estimate the threat posed by localized prostate cancer. No significant financial relationships to disclose.

TNM Staging in Colorectal Cancer: T Is for T Cell and M Is for Memory

Immune cell infiltration is a common feature of many human solid tumors. Recently, increased infiltration of tumors with cytotoxic CD8-positive T cells has been correlated with prolonged survival in multivariate analyses in a variety of epithelial cell cancers, including small-cell lung carcinoma; carcinomas of the endomentrium, bile duct, esophagus, and urothelium; pancreatic adenocarcinoma; and hepatocellular carcinomas. In this issue of Journal of Clinical Oncology, Mlecnik et al suggest that immune cell infiltration of colorectal cancer by cytotoxic CD8-positive and memory CD45ROpositive T cells has prognostic discriminatory power that is superior to standard staging systems (ie, American Joint Committee on Cancer– International Union Against Cancer–TNM). The authors examined more than 400 patients with colorectal cancer, quantitated the density of tumor-infiltrating T cells, devised an immune scoring system (higher scores reflecting greater CD8-positive and CD45RO-positive T-cell density), and correlated the immune scores with clinical outcome. The results demonstrate two key findings: patients with high immune scores have increased disease-free and overall survival as compared with patients whose tumors demonstrate low immune scores, and the immune score was superior in predicting disease outcome as compared with a host of important prognostic clinical parameters, including TNM staging. The authors further observed that there was an inverse correlation between immune cell density and tumor stage. In patient samples with the greatest immune cell density, the majority (60%) were tumor in situ or T1 stage tumors. In contrast, only 18% of T4 tumors demonstrated high-density T-cell infiltrates. Moreover, there were no tumor in situ or T1 stage disease specimens showing weak immune cell density scores, whereas 45% of T4 tumors demonstrated low immune scores. The data suggest that even with minimal tumor invasion, patients with a low immune score will be likely to experience a disease relapse. For these patients, surgery may not be curative. Remarkably, the prognostic significance of the immune score was retained regardless of whether the tumor tissue was derived from a patient with stage I or stage IV colorectal cancer. The study by Mlecnik et al is the culmination of several observations this investigative group has made over the last few years. Their initial observation, that a high density of memory CD8-positive T cells was associated with decreased evidence of early metastasis and increased survival in colorectal cancer, was followed by the development of an immune gene signature, associated with type I adaptive immunity, that correlated with decreased cancer recurrence. Moreover, in the same study, the investigators demonstrated that the type, density, and location of the T-cell infiltrate in the tumor were prognostically important. Further evaluations defined the importance of the memory T-cell phenotype and demonstrated the loss of coordinated functional immunity with the evolution of the tumor to a metastatic phenotype. A focused investigation of patients with earlystage colorectal cancer suggested that a multimarker panel of CD45RO-positive and CD8-positive T cells and cytotoxicity-related genes could predict prognosis even in these patients with minimal disease. Taken together, these studies laid the foundation for the immune score presented by Mlecnik et al as a clinical prognostic marker at any stage of colorectal cancer. Is the immune score presented in the Mlecnik et al study definitive? There are a few issues that remain to be addressed. The first issue is a better definition of the contribution of T regulatory cells to an immune score in colorectal cancer. CD4-positive T regulatory cells, as assessed by FOXP3 expression, have been shown to potentially modulate the antitumor response by suppressing the activity of CD8positive cytotoxic T cells and have been demonstrated to be a prognostic marker for disease outcome in several types of cancers. A high density of intratumoral FOXP3-positive T regulatory cells has been associated with poor outcomes in multiple solid tumors, including ovarian, pancreatic, and hepatocellular carcinoma. However, in colorectal cancer, studies of infiltrating FOXP3-expressing cells suggest the opposite: that regulatory T cells in the tumor are associated with an improved prognosis. Investigators evaluating nearly 1,000 tumor specimens from patients with stages II and III colorectal cancer demonstrated in multivariate analysis that highdensity intratumoral FOXP3-positive T cells were associated with improved survival (P .001). In a much smaller evaluation of 40 colorectal cancers, increased intratumoral T regulatory cells were correlated with limited versus metastatic disease. An additional study assessed the tumors of approximately 50 patients with relapsed colorectal cancer undergoing chemotherapy, and found that high intratumoral FOXP3-positive T-cell infiltrate was associated with benefits in overall survival (P .0005) and progression-free survival (P .0009). Colorectal cancer may be uniquely suited to a beneficial prognostic response to infiltrating T regulatory cells. In states of chronic gastrointestinal inflammation, such as inflammatory bowel disease, absolute mucosal T regulatory cell numbers are increased as a JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L S VOLUME 29 NUMBER 6 FEBRUARY 2

Hypofractionated Concomitant Intensity-Modulated Radiotherapy Boost for High-Risk Prostate Cancer: Late Toxicity

To report the acute and late toxicities of patients with high-risk localized prostate cancer treated using a concomitant hypofractionated, intensity-modulated radiotherapy boost combined with long-term androgen deprivation therapy. A prospective Phase I-II study of patients with any of the following: clinical Stage T3 disease, prostate-specific antigen level ≥ 20 ng/mL, or Gleason score 8-10. A dose of 45 Gy (1.8 Gy/fraction) was delivered to the pelvic lymph nodes with a concomitant 22.5 Gy prostate intensity-modulated radiotherapy boost, to a total of 67.5 Gy (2.7 Gy/fraction) in 25 fractions within 5 weeks. Image guidance was performed using three gold seed fiducials. The National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0, and Radiation Therapy Oncology Group late morbidity scores were used to assess the acute and late toxicities, respectively. Biochemical failure was determined using the Phoenix definition. A total of 97 patients were treated and followed up for a median of 39 months, with 88% having a minimum of 24 months of follow-up. The maximal toxicity scores were recorded. The grade of acute gastrointestinal toxicity was Grade 0 in 4%, 1 in 59%, and 2 in 37%. The grade of acute urinary toxicity was Grade 0 in 8%, 1 in 50%, 2 in 39%, and 3 in 4%. The grade of late gastrointestinal toxicity was Grade 0 in 54%, 1 in 40%, and 2 in 7%. No Grade 3 or greater late gastrointestinal toxicities developed. The grade of late urinary toxicity was Grade 0 in 82%, 1 in 9%, 2 in 5%, 3 in 3%, and 4 in 1% (1 patient). All severe toxicities (Grade 3 or greater) had resolved at the last follow-up visit. The 4-year biochemical disease-free survival rate was 90.5%. A hypofractionated intensity-modulated radiotherapy boost delivering 67.5 Gy in 25 fractions within 5 weeks combined with pelvic nodal radiotherapy and long-term androgen deprivation therapy was well tolerated, with low rates of severe toxicity. The biochemical control rate at early follow-up has been promising. Additional follow-up is needed to determine the long-term biochemical control and prostate biopsy results.

High-Dose-Rate Brachytherapy Boost for Prostate Cancer: Comparison of Two Different Fractionation Schemes

This is a retrospective study comparing our experience with high-dose-rate (HDR) brachytherapy boost for prostate cancer, using two different fractionation schemes, 600 cGy × 3 fractions (patient group 1) and 950 cGy × 2 fractions (patient group 2). A total of 165 patients were treated for prostate cancer using external beam radiation therapy up to a dose of 45 Gy, followed by an HDR brachytherapy prostate radiation boost. Between July 1997 and Nov 1999, 64 patients were treated with an HDR boost of 600 cGy × 3 fractions; and between June 2000 and Nov 2005, 101 patients were treated with an HDR boost of 950 cGy × 2 fractions. All but 9 patients had at least one of the following risk features: pretreatment prostate-specific antigen (PSA) level >10, a Gleason score ≥7, and/or clinical stage T3 disease. Median follow-up was 105 months for group 1 and 43 months for group 2. Patients in group 2 had a greater number of high-risk features than group 1 (p = 0.02). Adjusted for comparable follow-up, there was no difference in biochemical no-evidence-of-disease (bNED) rate between the two fractionation scheme approaches, with 5-year Kaplan-Meier estimates of 93.5% in group 1 and 87.3% in group 2 (p = 0.19). The 5-year estimates of progression-free survival were 86% for group 1 and 83% for group 2 (p = 0.53). Among high-risk patients, there were no differences in bNED or PFS rate due to fractionation. Results were excellent for both groups. Adjusted for comparable follow-up, no differences were found between groups.

The Role of Facial Palsy in Staging Squamous Cell Carcinoma of the Temporal Bone and External Auditory Canal

The role for facial palsy in the Pittsburgh staging system for squamous cell carcinoma (SCC) of the external auditory canal (EAC) is unclear. The objective of this study was to conduct a systematic review of published studies to determine the impact of facial palsy on survival outcomes. A search of MEDLINE, EMBASE, Cochrane Central Register of Clinical Trials, Cochrane, clinicaltrials.gov, and the National Guideline Clearinghouse databases was supplemented by hand searching. Articles selected for final analysis had individual subject data on staging and/or facial nerve function, outcome, and follow-up period. Data extracted included demographics, type and stage of cancer, survival, and facial nerve status. Of 3,046 citations identified by a systematic literature search, 21 case series including 348 subjects with SCC of the EAC met criteria for analysis. The overall and disease-specific survival for subjects with facial palsy were significantly worse than subjects without facial palsy, regardless of stage (p = 0.006 and p = 0.002, respectively). The overall survival outcome for subjects with facial palsy was significantly worse than subjects with stage PITT-2000 T3-designated cancer (p = 0.027) and demonstrated no statistically significant difference from stage PITT-2000 T4-designated cancer (p = 0.897). This pooled-data survival analysis for SCC of the EAC demonstrates that facial nerve involvement is associated with a poor outcome and that the survival outcomes for subjects with facial palsy more closely parallel the survival curves of advanced stage T4 disease. Disease with facial palsy should be classified as stage T4, in accordance with the PITT-2000 system.