Heterologous Liposarcomatous Differentiation in Malignant Phyllodes Tumor is Histologically Similar but Immunohistochemically and Molecularly Distinct from Well‐differentiated Liposarcoma of Soft Tissue

Malignant phyllodes tumor (PT) infrequently displays heterologous differentiation, and when present is most often liposarcomatous. We identified five cases of malignant PT with regions identical to well‐differentiated liposarcoma (WDLS) of soft tissue and evaluated them for MDM2 and CDK4 gene expression and amplification using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), respectively. Despite indistinguishable morphology all cases of malignant PT with WDLS‐like liposarcomatous differentiation were negative for MDM2 and CDK4 IHC and FISH, supporting different underlying pathogenesis.     

Dedifferentiated Liposarcoma of the Pleura: Report of a Case

We report a case of dedifferentiated liposarcoma of the pleura in a 59-year-old man who presented with pain in the right chest wall, 3 years after a routine chest X-ray showed a large tumorous mass. The resected tumor was composed of three distinct histological features: well-differentiated liposarcoma with low-grade leiom-yosarcomatous and low-grade osteosarcomatous components. To our knowledge, this is the first report of dedifferentiated liposarcoma of the pleura.     

Inflammatory Variant of Atypical Lipomatous Tumor/Well-Differentiated Liposarcoma of the Buccal Mucosa: An Overview and Case Report with a 10-Year Follow-Up

Liposarcomas of the oral cavity are rare. Those originating in the buccal mucosa cause challenging diagnostic and therapeutic issues since less than 40 cases of liposarcomas of the buccal mucosa and cheek have been reported in the worldwide literature. Herein, we present a case of atypical lipomatous tumor/well-differentiated liposarcoma affecting a 45-year-old female patient. Ultrasonography and magnetic resonance imaging confirmed a well-defined mass located in the right buccal mucosa, extending to the submucosal layers of the cheek. Histopathologically, a well-differentiated fatty neoplasm with presence of prominent stromal inflammatory cells was observed. Multifocally scattered bizarre hyperchromatic stromal cells, some of which multinucleated, were also observed. An immunohistochemical panel comprising vimentin, S-100, CD10, CD34, CD20, CD3, CD68, CD138, MDM2, Ki-67, and P53 was employed to better characterize the lesion. A local recurrence event occurred during a 10-year follow-up period. Surgical resection was performed during both episodes. We also provided an overview of demographic and clinicopathological characteristics, immunohistochemical features, imaging findings, and the differential diagnosis of liposarcoma of the oral cavity. Knowledge of the etiopathological and clinical aspects of this rare neoplasm is fundamental in order to rule out other conditions, including lipomatous lesions that affect the buccal mucosa.     

Palbociclib combined with endocrine therapy in heavily pretreated HR+/HER2- advanced breast cancer patients: Results from the compassionate use program in Spain (PALBOCOMP)

BackgroundThis study evaluated efficacy and safety of palbociclib, a CDK4/6 inhibitor, in heavily-pretreated hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR⁺/HER2^-) metastatic breast cancer (mBC) patients during the compassionate use program in Spain from February 2015 to November 2017.Patients and methodsPatient data were collected retrospectively from 35 hospitals in Spain. Patients with HR⁺/HER2^- mBC who had progressed on ≥4 treatments for advanced disease were eligible.ResultsA total of 219 patients received palbociclib in combination with aromatase inhibitors (110; 50.2%), fulvestrant (87; 39.7%), tamoxifen (8; 3.6%) or as single agent (10; 4.6%). Mean age of the patients was 58 years; 31 patients (16.1%) were premenopausal and 162 (83.9%) were postmenopausal at the beginning of treatment with palbociclib. Patients had received a median of 3 previous lines of endocrine therapy (ET) for advanced disease. Real-world tumor response (rwTR) and clinical benefit rate were 5.9% (n = 13) and 46.2% (n = 101), respectively. The median real world progression-free survival (rwPFS) was 6.0 months (95% CI 5.7–7.0) and the median overall survival was 19.0 months (95% CI 16.4–21.7). Subgroup analysis revealed a significant difference in median rwPFS in patients treated with palbociclib plus fulvestrant depending on the duration of prior treatment with fulvestrant monotherapy (>6 versus ≤6 months; HR 1.93, 95% CI 1.37–2.73, p < 0.001). The most frequently reported toxicities were neutropenia, asthenia, thrombopenia and anemia.ConclusionsPalbociclib can be an effective and safe treatment option in patients with heavily pretreated endocrine-sensitive mBC, especially in those with longer PFS to previous ET.     

Human Papillomavirus (HPV)-Related Carcinoma of the Oropharynx with Squamous Cell and Adenoid Cystic Carcinoma-Like Features: Report of a Case

We describe the heretofore unreported case of an HPV-related carcinoma of the palatine tonsil with distinct areas of squamous cell- and adenoid cystic carcinoma-like differentiation in a 54-year old patient. The morphological, immunophenotypic and molecular findings of the tumor are illustrated. We discuss the parallels between the tumor and HPV-related multiphenotypic sinonasal carcinoma (HMSC) which is well-known to exhibit adenoid cystic carcinoma-like features. A review of the literature of high-risk HPV-associated non-squamous carcinomas of the oropharynx is presented.     

Low Grade Papillary Sinonasal (Schneiderian) Carcinoma: A Series of Five Cases of a Unique Malignant Neoplasm with Comparison to Inverted Papilloma and Conventional Nonkeratinizing Squamous Cell Carcinoma

There have been a few case reports and one small series of low grade papillary sinonasal (Schneiderian) carcinomas (LGPSC) which mimic papillomas but have overtly invasive growth and which occasionally metastasize. We describe the morphologic, clinical, immunohistochemical, and molecular features of five patients with LGPSC compared with eight cases each of inverted papilloma (IP) and conventional nonkeratinizing squamous cell carcinoma (SCC) with papillary growth. All LGPSC were nested with predominantly pushing invasion, no stromal reaction, and frequent surface papillary growth. All consisted of one cell type only, with polygonal cells with round nuclei, no (or limited) cytologic atypia, low mitotic activity, and prominent neutrophilic infiltrate. One patient had slightly more infiltrative bone invasion, another lymphovascular, perineural, and skeletal muscle invasion, and a third nodal metastasis after 17 years. By comparison, IPs had bland cytology, neutrophilic microabscesses, mixed immature squamous, goblet cell, and respiratory epithelium, and extremely low mitotic activity. Nonkeratinizing SCCs had basaloid-appearing cells with nuclear pleomorphism, brisk mitotic activity, and apoptosis. All LGPSC were p63 positive. Mitotic activity and Ki67 indices were significantly higher for LGPSCs than IPs and significantly lower than NKSCCs, while p53 immunohistochemistry in LGPSC was identical to nonkeratinizing SCC and higher than for IP. Sequencing showed all five tumors to harbor a MUC6 mutation, one tumor to harbor CDKN2A and PIK3R1 mutations, and one tumor to harbor a NOTCH1 mutation. All LGPSC lacked EGFR and KRAS mutations and lacked copy number variations of any main cancer genes. At a median follow up of 12 months, two LGPSC recurred locally, and one patient died after massive local recurrences and nodal metastases. LGPSC is a distinct, de novo sinonasal carcinoma that can be differentiated from papillomas by morphology and selected immunohistochemistry.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12105-021-01335-3.     

The Yale University Experience of Early-Stage Invasive Lobular Carcinoma (ILC) and Invasive Ductal Carcinoma (IDC) Treated with Breast Conservation Treatment (BCT): Analysis of Clinical-Pathologic Features, Long-Term Outcomes, and Molecular Expression of COX-2, Bcl-2, and p53 as a Function of Histology

Abstract:  To evaluate our experience of the clinical-pathologic features and outcomes of early-stage Invasive Lobular (ILC) versus Invasive Ductal (IDC) carcinoma treated with breast conservation treatment (BCT). 142 ILC and 1,760 IDC patients were treated with BCT at our institution. All patients underwent breast conserving surgery and radiation therapy (median total dose: 64 Gy). Clinical-pathologic and outcome parameters were analyzed to detect differences between the two cohorts. In addition, COX-2, Bcl-2, and p-53 expression was analyzed from our existing tissue micro-array database. Median follow-up was 6.8 years. A higher percentage of ILC patients presented at >40 years of age (94% ILC versus 89% IDC, p = 0.0353) and had more mammographically occult tumors (p < 0.002). There were no significant differences in T stage, nodal status, family history, final margin, ER/PR/HER-2 status or triple negative tumors (all p-values >0.05). From the immuno-histochemical analysis, expression of p53, COX-2, and Bcl-2 did not differ significantly (all p-values >0.05) between the two cohorts. At 10 years, there was no difference in breast relapse (20% versus 13%, p = 0.25), distant relapse (26% versus 20%, p = 0.28), cause-specific survival (72% versus 84%, p = 0.09) and OS (68% versus 78%, p = 0.08). Patients with ILC had higher contralateral breast relapses (26% versus 12%, p = 0.0006). Patients with early-stage ILC have comparable outcomes to IDC when treated with BCT. Because of the higher risk of contralateral breast cancers for ILC patients, careful evaluation of the contralateral breast will be important in the follow-up of these patients. Future investigations of chemo-preventive strategies to decrease contralateral breast cancers are warranted.     

Role of the CDK Inhibitor p27 (Kip1) in Mammary Development and Carcinogenesis: Insights from Knockout Mice

The cyclin-dependent kinase inhibitor p27 (Kip1) is an important cell cycle regulatory gene in breast cancer, and decreased p27 expression is associated with poor prognosis. Some investigations of its role in mammary development have demonstrated reduced cyclin D1 expression and consequent lack of lobuloalveolar development, but others have found increased cyclin E-Cdk2 activity and increased proliferation balanced by increased apoptosis. It is unclear at present why these apparently divergent results have been obtained. Mice with reduced p27 gene dosage alone do not develop mammary carcinomas but do display substantially shorter tumor latency upon overexpression of erbB2, consistent with a role for p27 as a mammary tumor suppressor gene. In this review we summarize these and other data addressing the role of p27 in normal mammary epithelium and experimental models of mammary carcinogenesis.     

Totally Laparoscopic Anatomical Hepatectomy Exposing the Major Hepatic Veins from the Root Side: a Case of the Right Anterior Sectorectomy (with Video)

Laparoscopic hepatectomy has rapidly evolved recently; 1–5 however, laparoscopic anatomical hepatectomy has yet to become widely used, although anatomical hepatectomy is ideal, especially for curative treatment of hepatocellular carcinoma, and is widely accepted via open approach. 6–10 This is because good-experienced skills, for example, exposing Glissonean pedicles and hepatic veins on the cutting plane, are required in order to perform anatomical hepatectomy via a pure laparoscopic approach. We obtained good results for various totally laparoscopic anatomical hepatectomies using the standardized techniques. We exposed the major hepatic veins from the root side by utilizing the unique view from the caudal side in the laparoscopic approach, and moved CUSA from the root side toward the peripheral side to avoid splitting the bifurcation of the hepatic vein. 11–13 We performed totally laparoscopic anatomical hepatectomy for 47 patients from August, 2008, to December, 2012 (Table 1). In most types of anatomical hepatectomy, the mean blood loss was <500 ml. Conversion to open surgery was required in two patients. Postoperative complications were prolonged ascites in two, peroneal palsy in two, and biloma in one. Mortality was zero. The embedded video demonstrates totally laparoscopic right anterior sectorectomy. In conclusion, our standardized techniques make laparoscopic anatomical hepatectomy more feasible.

Impact of clinical and pathological subtypes of carcinoma in situ (CIS) of the bladder: Lessons learned from long-term follow-up of a series of CIS patients treated with BCG

ObjectiveSome attempts have previously been made to stratify patients with CIS for the purpose of risk-adapted clinical management and clinical trial design. In particular, two classification systems have been proposed: clinical classification, comprising primary (P-CIS), concomitant (C-CIS), and secondary (S-CIS) disease, and pathological classification, comprising P-CIS, cTa-CIS, and cT1-CIS. The aim of the present study was to assess the impact of both classifications on BCG response, recurrence-free survival (RFS), progression-free survival (PFS), overall survival (OS), and cancer-specific survival (CSS).Patients and MethodsWe performed a retrospective analysis of 386 patients with bladder CIS, with or without associated cTa/cT1 disease, treated with BCG instillations between 2008 and 2015. Patients were stratified according to the two classification systems. Cox multivariate regression models were used to assess the impact of these subtypes on BCG response, RFS, PFS, OS, and CSS. We also performed a cumulative meta-analysis according to PRISMA guidelines.ResultsThe median follow-up was 70.5 months. According to the clinical classification, 34 (8.8%) patients had P-CIS, 81 (21%) S-CIS, and 271 (70.2%) C-CIS. The pathological classification showed 34 (8.8%) patients to have P-CIS, 190 (49.2%) cTa-CIS, and 162 (42%) cT1-CIS. In the overall cohort, BCG response was reported in 296 (76.7%); 159 (41.2%) had recurrence, 55 (14.2%) had progression, and 67 (17.4%) underwent radical cystectomy. Death from any cause was recorded in 135 (35%) and death from urothelial carcinoma in 38 (9.9%). Cox multivariate regression analysis showed that neither clinical classification nor pathological classification is an independent predictive factor for BCG response, RFS, PFS, OS, or CSS after adjusting for confounders. In the pooled meta-analysis, two studies and the present series were included for evidence synthesis, recruiting a total of 941 patients. We found no statistically significant difference across the groups for both classifications with respect to BCG response, RFS, PFS, and CSS.ConclusionsCurrently, the supporting evidence for an impact of clinical classification and pathological classification on oncological outcomes of CIS of the bladder is insufficient to justify their use to guide clinical management or follow-up.     

Complete remission of liver metastases from colorectal cancer by treatment with a hepatic artery infusion (HAI) of interleukin-2-based immunochemotherapy: reports of three cases

In an attempt to improve the therapeutic efficacy against liver metastases, a hepatic arterial infusion (HAI) of interleukin-2 (IL-2)-based immunochemotherapy for anticipating the regional potentiation of hepatic lymphokine-activated killer (LAK)/tumor-infiltrating lymphocytes (TIL) was initiated. We present herein the cases of three patients with multiple liver metastases from colorectal cancer in whom complete remission was achieved by treatment with an HAI of IL-2 in combination with mitomycin C (MMC) and 5 fluorouracil (5-FU). These patients received an HAI of IL-2 at 8 x 10⁵ JRU, 5-FU at 250 mg daily, and MMC at 4 mg once weekly for 3 weeks, being the induction regimen, after which they were discharged on maintenance therapy consisting of IL-2 at 2 X 10⁶ JRU, 5-FU at 250 mg twice weekly, and MMC at 4 mg once weekly. It was evident from the liver CT scan taken after 2–3 months that the metastatic foci seen before therapy had clearly disappeared, while the serum carcinoembryonic antigen (CEA) had decreased to normal levels in all three patients. Pancytopenia was seen in one patient, but other laboratory studies of the hepatic and renal parameters were normal. The total lymphocyte count in the peripheral blood showed a mild decrease, while the lymphocyte phenotype study showed a notable increase in CD4⁺ cells and a decrease in CD8⁺ cells, with an elevation of a 4/8 ratio, in all cases during therapy. One patient relapsed with pelvic recurrence 14 months after the initiation of therapy, but the other two patients are still in remission 25 and 22 months after the initiation of therapy.     

Papillary cystic neoplasm (PCN) of the pancreas with lymph node metastasis: Case report of a 77-year-ood woman and a review of 198 reported cases

A case of papillary cystic neoplasm (PCN) of the pancreas in a 77-year-old woman, the oldest patient in the English literature, is reported. Distal pancreatectomy with regional lymphadenectomy was performed for the tumor in the pancreatic tail. Postoperative pathology examination revealed a metastatic lesion in one of the regional lymph nodes. This patient is well doing without recurrence 5 years after surgery. One hundred and ninety-eight cases of PCN, including the present case, have been reported in the English literature. The patients were aged from 2 to 77 years (mean, 25.8); there were 187 females and 11 males. Sixteen patients with metastasis, 22 with local invasion, and 3 with peritoneal dissemination were reported. Complete resection of the tumor was performed in 151 patients, including 6 with metastasis and 11 with local invasion. Only one patient died of recurrent tumor.     

Switch from bicarbonate hemodialysis to hemodiafiltration with online regeneration of the ultrafiltrate (HFR): effects on nutritional status, microinflammation, and beta-microglobulin

BACKGROUND: Hemodiafiltration (HFR) with on-line regeneration of the ultrafiltrate, a technique of hemodiafiltration in which the ultrafiltrate passes through a cartridge containing uncoated charcoal, has been shown to be safe, simple, and well tolerated and has been claimed to improve nutritional status or to prevent its deterioration while decreasing the inflammatory response via a reduced production of proinflammatory cytokines. The purpose of the present prospective study was to ascertain whether HRF improves the nutritional status, reduces microinflammation, and decreases serum beta2-microglobulin levels in patients with end-stage renal disease (ESRD). METHODS: Eight patients, four males and four females, with a mean age of 49.4 +/- 16.8 years, stable on hemodialysis over a period of 8.7 +/- 6.1 years and on standard 4-4.5 h three-times-a-week bicarbonate hemodialysis, were switched to three-times-a-week, 4-h HFR. At baseline and every two months for 12 months at mid-week, serum levels of urea, creatinine, albumin, total cholesterol, C-reactive protein, fibrinogen, complement, ferritin, beta2-microglobulin, intact parathyroid hormone (PTH), hemoglobin concentrations, and hematocrit and the EPO weekly dose were determined. At baseline and at the end of the study, the Malnutrition Inflammatory Score (MIS) was calculated. RESULTS: Nutritional and inflammatory parameters remained constant during the 12-month period of the study. After 12 months of HFR, the MIS trended to be lower, but the difference was not statistically significant. Serum beta2-microglobulin and PTH levels remained constant during all time intervals. Neither hematocrit nor hemoglobin changed over the course of the study as well as the weekly EPO dose. CONCLUSION: The change from bicarbonate hemodialysis to HFR was safe and well tolerated but was not associated with an improvement of nutritional and inflammatory parameters or a reduction of serum beta2-microglobulin levels.     

Macrofollicular Variant of Follicular Thyroid Carcinoma (MV-FTC) with a Somatic DICER1 Gene Mutation: Case Report and Review of the Literature

Benign thyroid lesions such as multinodular goiter and adenomatoid nodules are well-circumscribed lesions displaying a macrofollicular growth pattern and lack of nuclear atypia. The highly unusual macrofollicular variant of follicular thyroid carcinoma (MV-FTC) mirrors these attributes and is thereby misclassified by cytological examination of fine-needle aspiration biopsies. The MV-FTC diagnosis is instead suggested following histological investigation, in which malignant attributes, most commonly capsular invasion, are noted. The bulk of MV-FTCs described in the literature arise in younger female patients and carry an excellent prognosis. A recent coupling to mutations in the DICER1 tumor suppressor gene has been proposed, possibly indicating aberrancies in micro-RNA (miRNA) patterns as responsible of the tumorigenic process. We describe the cytological, histological and molecular phenotype of a 35 mm large MV-FTC arising in the right thyroid lobe of a 33-year-old female with a family history of multinodular goiter. The tumor was encapsulated and strikingly inconspicuous in terms of cellularity and atypia, but nevertheless displayed multiple foci with capsular invasion. A next-generation molecular screening of tumor DNA revealed missense variants in DICER1 (p. D1709N) and MET (p. T1010I), but no established fusion gene events. After sequencing of germline DNA, the DICER1 mutation was confirmed as somatic, while the MET variant was constitutional. The patient is alive and well, currently awaiting radioiodine treatment. This MV-FTC mirrors previous publications, suggesting that these tumors carry a favorable prognosis and predominantly arise in younger females. Moreover, DICER1 mutations should be considered a common driver event in the development of MV-FTCs.     

Comparison of the Glidescope(R), the Pentax AWS(R), and the Truview EVO2(R) with the Macintosh laryngoscope in experienced anaesthetists: a manikin study

Background: The Pentax Airwayscope®, the Glidescope®, and the TruviewEVO2® constitute three novel laryngoscopes that facilitatevisualization of the vocal cords without alignment of the oral,pharyngeal, and tracheal axes. We compared these devices withthe Macintosh laryngoscope in a simulated easy and difficultlaryngoscopy. Methods: Thirty-five experienced anaesthetists were allowed up to threeattempts to intubate in each of four laryngoscopy scenariosin a Laerdal® SimMan® manikin. The time required toperform tracheal intubation, the success rate, number of intubationattempts and of optimization manoeuvres, and the severity ofdental compression were recorded. Results: In the simulated easy laryngoscopy scenarios, there was no differencebetween the study devices and the Macintosh in success of trachealintubation. In more difficult tracheal intubation scenarios,the Glidescope® and Pentax AWS®, and to a lesser extentthe Truview EVO2® laryngoscope demonstrated advantages overthe Macintosh laryngoscope including a better view of the glottis,greater success of tracheal intubation, and ease of device use.The Pentax AWS® was more successful in achieving trachealintubation, required less time to successfully perform trachealintubation, caused less dental trauma, and was considered bythe anaesthetists to be easier to use. Conclusions: The Pentax AWS® laryngoscope demonstrated more advantagesover the Macintosh laryngoscope than either the Truview EVO2®or the Glidescope® laryngoscope, when used by experiencedanaesthetists in difficult tracheal intubation scenarios.     

Efficacy of trastuzumab emtansine (T-DM1) and lapatinib after dual HER2 inhibition with trastuzumab and pertuzumab in patient with metastatic breast cancer: Retrospective data from a French multicenter real-life cohort

PurposeTrastuzumab-emtansine (T-DM1), as well as lapatinib plus capecitabine were proven effective in two Phase III studies, following first-line trastuzumab plus a taxane. The introduction of dual HER2 blockade by trastuzumab and pertuzumab as first-line has positioned T-DM1 into second-line, and lapatinib plus capecitabine beyond, without formal evaluation of these strategies.MethodsESME Data Platform (NCT03275311) included individual data from all patients aged ≥18 years, in whom first-line treatment for metastatic breast cancer (MBC) was initiated between January 1, 2008 and December 31, 2016 in one of the 18 French Comprehensive Cancer Centers. The efficacy of T-DM1 and lapatinib plus capecitabine combination, following double blockade associating trastuzumab and pertuzumab were evaluated in this national real-life database. Eligibility criteria were: female, MBC, HER2+ tumor, first-line taxane-based chemotherapy and dual HER2-blockage by trastuzumab plus pertuzumab. Cohort A received second-line T-DM1, and Cohort B second-line T-DM1 and third or fourth-line lapatinib plus capecitabine.ResultsCohort A comprised 233 patients, and Cohort B 47 patients. Median progression-free survival (PFS) was 7.1 months in Cohort A and 4.6 months in Cohort B. Median overall survival were 36.7 months and 12.9 months, respectively. PFS was significantly dependent on the preceding treatment line's duration. In cohort A, HER2 expression status was a significant predictive factor of PFS.ConclusionFirst-line trastuzumab plus pertuzumab do not markedly diminish T-DM1's efficacy in second-line. Similarly, sequential treatment with trastuzumab plus pertuzumab then T-DM1 does not noticeably modify the efficacy of lapatinib plus capecitabine.     

Usefulness of prostate-specific antigen (PSA) rise as a marker of prostate cancer in men treated with dutasteride: lessons from the REDUCE study

Study Type – Prognostic (RCT) Level of Evidence 1b What's known on the subject? and What does the study add? Previous studies used the decrease in PSA after 6 months of dutasteride treatment as a new ‘baseline’ PSA value from which subsequent rises may serve as a warning for prostate cancer; however, PSA tends to continue to decrease as dutasteride treatment continues. By comparing positive biopsy rates in the REDUCE study using any rise from nadir in the dutasteride arm and standard PSA decision criteria (NCCN) in the placebo arm, we demonstrated that the ability to detect prostate cancer and high grade prostate cancer is maintained with dutasteride treatment.

OBJECTIVES

? To determine if dutasteride‐treated men can be monitored safely and adequately for prostate cancer based on data from the Reduction by Dutasteride in Prostate Cancer Events (REDUCE) study. ? To analyse whether the use of treatment‐specific criteria for repeat biopsy maintains the usefulness of prostate‐specific antigen (PSA) level for detecting high grade cancers.

PATIENTS AND METHODS

? The REDUCE study was a randomized, double‐blind, placebo‐controlled investigation of whether dutasteride (0.5 mg/day) reduced the risk of biopsy‐detectable prostate cancer in men with a previous negative biopsy. ? The usefulness of PSA was evaluated using biopsy thresholds defined by National Comprehensive Cancer Network guidelines in the placebo group and any rise in PSA from nadir (the lowest PSA level achieved while in the study) in the dutasteride group. ? The number of cancers detected on biopsy in the absence of increased/suspicious PSA level as well as sensitivity, specificity, positive predictive value and negative predictive value for high grade prostate cancer detection were analysed by treatment group. ? Prostate cancer pathological characteristics were compared between men who did and did not meet biopsy thresholds.

RESULTS

? Of 8231 men randomized, 3305 (dutasteride) and 3424 (placebo) underwent at least one prostate biopsy during the study and were included in the analysis. ? If only men meeting biopsy thresholds underwent biopsy, 25% (47/191) of Gleason 7 and 24% (7/29) of Gleason 8–10 cancers would have been missed in the dutasteride group, and 37% (78/209) of Gleason 7 and 22% (4/18) Gleason 8–10 cancers would have been missed in the placebo group. ? In both groups, the incidence of Gleason 7 and Gleason 8–10 cancers generally increased with greater rises in PSA. ? Sensitivity of PSA kinetics was higher and specificity was lower for the detection of Gleason 7–10 cancers in men treated with dutasteride vs placebo. ? Men with Gleason 7 and Gleason 8–10 cancer meeting biopsy thresholds had greater numbers of positive cores, percent core involvement, and biopsy cancer volume vs men not meeting thresholds.

CONCLUSION

? Using treatment‐specific biopsy thresholds, the present study shows that the ability of PSA kinetics to detect high grade prostate cancer is maintained with dutasteride compared with placebo in men with a previous negative biopsy. ? The sensitivity of PSA kinetics with dutasteride was similar to (Gleason 8–10) or higher than (Gleason 7–10) the placebo group; however, biopsy decisions based on a single increased PSA measurement from nadir in the dutasteride group resulted in a lower specificity compared with using a comparable biopsy threshold in the placebo group, indicating the importance of confirmation of PSA measurements.