Patterns of Recurrence and Survival After Pelvic Treatment for Locally Advanced Penile Cancer

BACKGROUND: Penile cancer (PeCa) is rare, and the survival of patients with advanced disease remains poor. A better understanding of where treatment fails could aid the development of new treatment strategies. OBJECTIVE: To describe the disease course after pelvic lymph node (LN) treatment for PeCa. DESIGN, SETTING, AND PARTICIPANTS: We retrospectively analysed 228 patients who underwent pelvic LN treatment with curative intent from 1969 to 2016. The main treatment modalities were neoadjuvant chemotherapy, chemoradiation, and pelvic LN dissection. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: In the case of multiple recurrence locations, the most distant location was taken and recorded as follows: local (penis), regional (inguinal and pelvic LN), and distant (any other location). A competing risk analysis was used to calculate the time to recurrence per location, and a Kaplan-Meier analysis was used for overall survival (OS). RESULTS AND LIMITATIONS: The median follow-up of the surviving patients was 79 mo. The reason for pelvic treatment was pelvic involvement on imaging (29%), two or more tumour-positive inguinal LNs (61%), or inguinal extranodal extension (52%). More than half of the patients (61%) developed a recurrence. The median recurrence-free survival was 11 mo. The distribution was local in 9%, regional in 27%, and distant in 64% of patients. The infield control rate of nonsystemically treated patients was 61% (113/184). From the start of pelvic treatment, the median OS was 17 mo (95% confidence interval 12–22). After regional or distant recurrence, all but one patient died of PeCa with median OS after a recurrence of 4.4 (regional) and 3.1 (distant) mo. This study is limited by its retrospective nature. CONCLUSIONS: The prognosis of PeCa patients treated on their pelvis who recur despite locoregional treatment is poor. The tendency for systemic spread emphasises the need for more effective systemic treatment strategies. PATIENT SUMMARY: In this report, we looked at the outcomes of penile cancer patients in an expert centre undergoing various treatments on their pelvis. We found that survival is poor after recurrence despite locoregional treatment. Therefore, better systemic treatments are necessary

Culture and institutions:How economic freedom and long-term orientation interactively influence corporate social responsibility

Studies of international differences in firm behavior tend to consider either institutional or cultural factors. Focusing on corporate social responsibility (CSR), we conjecture that not only both institutions and culture need to be taken into account, but also the interaction between these two sets of factors. We theorize that the institutions associated with economic freedom in combination with the cultural trait long-term orientation positively influences CSR practices. Panel data of 5023 companies from 41 countries confirm this expectation. This finding pertains both to long-term orientation at the level of the society and at the level of the company. Our findings support calls for more attention to interactive effects of cultures and institutions

Technological competition, innovation motive and corporate social responsibility:Evidence from top managers of European SMEs

Various motives have been proposed for firms to engage in corporate social responsibility (CSR), but no attention has been paid to innovation as a motive to engage in CSR. In this paper we explore the role of this motive and hypothesize that it is particularly important for companies facing intensive technological competition. We find support for this in a sample of 2579 top managers of small and medium sized enterprises from 12 European countries. The innovation motive mediates the relationship between technological competition and CSR and is the most (second most) important motive for environmental and social CSR, respectively

National culture and environmental responsibility research revisited

Highlights • Findings regarding the relationship between national culture and corporate environmental responsibility (CER) are conflicting. • We perform three robustness analyses, regarding dimensions of national culture, measures of CER, and estimation techniques. • Our findings show that no dimension of national culture has a fully robust relationship with CER

Prognostic factors for occult inguinal lymph node involvement in penile carcinoma and assessment of the high-risk EAU subgroup: A two-institution analysis of 342 clinically node-negative patients

Background: The European Association of Urology (EAU) guidelines advise an elective bilateral lymphadenectomy in clinically node-negative (cN0) patients with high-risk penile carcinoma (â¥pT2, G3, or lymphovascular invasion [LVI]). Objective: Our aim was to assess prognostic factors for occult metastasis and to determine whether current EAU guidelines accurately stratify patients at high risk. Design, setting, and participants: Data of 342 cN0 patients with histologically proven invasive penile squamous cell carcinoma who had undergone the current dynamic sentinel node biopsy (DSNB) protocol were analysed. A complete ipsilateral inguinal lymphadenectomy was only done if the sentinel node was tumour positive. Measurements: The presence of occult metastasis was established by preoperative ultrasound and tumour-positive fine-needle aspiration cytology, tumour-positive sentinel nodes, and groin metastases during follow-up after a negative DSNB procedure. Median follow-up was 31 mo. Results and limitations: Sixty-eight of 342 patients (20%) and 87 of 684 groins (13%) had occult nodal involvement including 6 patients (2%) with a groin metastasis after negative DSNB. Corpus spongiosum invasion, corpus cavernosum invasion, histologic grade, and LVI were each significant prognosticators for occult metastasis on univariate analysis. On multivariate analysis, grade (odds ratio [OR] : 3.3 for intermediate and 4.9 for poor, respectively) and LVI (OR: 2.2) remained predictive factors. In total, 245 patients (72%) were classified high risk according to EAU guidelines. Among them, the incidence of occult metastasis was 23% (57 of 245). A potential limitation of this study is the lack of external review. Conclusions: Histologic grade and LVI are independent prognostic factors for occult metastasis in penile carcinoma. Although both predictors are incorporated into the current EAU guidelines, the stratification of patients needing a lymph node dissection is inaccurate. Approximately 77% of high-risk patients (188 of 245) would have had a negative bilateral inguinal lymphadenectomy. For the time being, DSNB is considered a more suitable staging method than EAU risk stratification for an accurate determination of patients who require lymph node dissection. © 2010 European Association of Urology. Published by Elsevier B.V. All rights reserved.Link_to_subscribed_fulltex

F-18 Fluorodeoxyglucose Positron Emission Tomography with Computed Tomography Has High Diagnostic Value for Pelvic and Distant Staging in Patients with High-risk Penile Carcinoma

Background: For penile cancer patients with pelvic metastases, multimodal treatment is advised, but pelvic lymph node metastases are often found upon surgical resection only. Early selection for multimodal treatment requires reliable noninvasive staging. Objective: To evaluate the diagnostic value of 18F-fluorodeoxyglucose positron emission tomography with computed tomography (FDG-PET/CT) for staging pelvic lymph nodes and distant metastases in high-risk penile cancer patients. Design, setting, and participants: FDG-PET/CT scans performed in patients with clinically overt inguinal lymph node metastases and/or high-risk primary tumors (bulky T3 or T4) were retrospectively analyzed. Outcome measurements and statistical analysis: All scans were reviewed by two independent nuclear medicine physicians staging the pelvic nodes and distant metastases. FDG-PET/CT findings were compared with histology after node dissection if available, or with positive imaging or follow-up of at least 1 yr. Results and limitations: Between 2006 and 2016, 61 patients met the inclusion criteria. For staging of pelvic nodes, sensitivity was 85% (specificity 75%, negative predictive value [NPV] 90%, and positive predictive value [PPV] 65%). For the detection of distant metastases, FDG-PET/CT had a PPV of 93%. Results are limited by the retrospective design and the lack of direct comparison with CT scanning alone. Conclusions: FDG-PET/CT has high sensitivity and a high NPV for staging of pelvic lymph nodes in high-risk penile cancer. It also has a high PPV for the detection of distant metastases, which were found in 23% of patients. Therefore, FDG-PET/CT enables early selection for multimodal treatment of patients with pelvic metastases and may help avoid futile treatment of patients with distant metastases. Patient summary: We studied whether positron emission tomography with computed tomography (PET/CT) scans in patients with advanced penile cancer can detect metastases before lymph node surgery is done. PET/CT scans can detect or rule out pelvic lymph node metastases, and can detect distant metastases. This helps in making timely treatment decisions (before surgery). In cN2–3 and/or bulky T3–4 penile cancer patients, 18F-fluorodeoxyglucose positron emission tomography with computed tomography (FDG-PET/CT) has high sensitivity (85%) for the detection of pelvic metastases. FDG-PET/CT aids in early selection of patients with pelvic metastases for multimodal treatment and helps in avoiding futile treatment in M+ patients

A Phase II, single-arm trial of neoadjuvant axitinib plus avelumab in patients with localized renal cell carcinoma who are at high risk of relapse after nephrectomy (NEOAVAX)

Surgery is the standard treatment for nonmetastatic renal cell carcinoma. Despite curative intent, patients with a high risk of relapse have a 5-year metastasis-free survival rate of only 30% and prevention of recurrence is an unmet need. In a Phase III trial (JAVELIN Renal 101), progression-free survival of axitinib + avelumab was superior to sunitinib with a favorable objective response rate and no added toxicity profiles as known for axitinib or avelumab single agent. NEOAVAX is designed as open label, single arm, Phase II trial with a Simon's two-stage design evaluating neoadjuvant axitinib + avelumab followed by complete surgical resection in 40 patients with high-risk nonmetastatic clear-cell renal cell carcinoma. Primary end point is remission of the primary tumor (RECIST 1.1; Response Evaluation Criteria In Solid Tumors) following neoadjuvant therapy. Secondary end points include disease-free survival, overall survival, rate of metastasis and local recurrence, safety, and tolerability. Exploratory end points include investigation of effects on neoangiogenesis, immune infiltrates and myeloid-derived suppressor cell components to support a rationale for the combined use of axitinib and avelumab (NCT03341845)

Topographic distribution of first landing sites of lymphatic metastases from patients with renal cancer

Introduction and Objective: Adjuvant studies with checkpoint inhibitors have attracted new interest in accurate pathological lymph node (LN) staging in renal cell carcinoma. Sentinel lymph node (SN) studies in cN0 patients revealed the pattern of lymphatic radiotracer drainage from renal tumors. The aim of this study was to describe the location of single- or oligometastatic LN and analyze if the topography of these first landing sites matches the drainage pattern observed in SN studies of renal tumors. Materials and Methods: We collected data from 8 referral centers from 1990 to 2018 of all patients with pT1-4 cN0 or cN1 M0 renal cell carcinoma with pathologically confirmed single- or oligometastases in locoregional LN. The location of LN metastases, number, size of metastatic LN, and survival were analyzed using descriptive statistics with SPSS version 22 (IBM, Chicago, IL). Results: From 3,794 patients with histologically confirmed pN1, a total of 76 patients (2%) with single- or oligometastatic pN1 were identified, of whom 24 (31.6%) and 52 (68.4%) were cN0 and cN1, respectively. On the left side, LN metastases were predominantly located in the para-aortal (48.0%; 95% confidence interval [CI] 29.22–63.12%) and hilar (31.42%; 95% CI 17.4–49.4%) area. On the right side, metastases located in retrocaval (26.82%; 95% CI 14.7–43.2%), hilar (26.82%; 95% CI 14.7–43.2%), interaortocaval (26.82%; 95% CI 14.7–43.2%), and paracaval (17.07%; 95% CI 7.6–32.6%) LNs. These landing sites exactly matched the lymphatic drainage pattern of intratumorally injected radiotracer reported in SN studies for both sides. Conclusions: Single- or oligometastatic LNs in renal cancer are mainly located in the hilar, retro-, para, and interaortocaval region on the right side and para-aortal region on the left side. These first landing sites match the drainage pattern reported in SN trials