Human chorionic gonadotropin-positive seminoma patients: A registry compiled by the global germ cell tumor collaborative group (G3).

BACKGROUND: The prognostic role of human chorionic gonadotropin (hCG) and lactate dehydrogenase (LDH) serum levels in seminoma patients remains uncertain. This observational study evaluates the prognostic impact of tumour marker levels, and other clinicopathological findings, in hCG-positive seminoma patients. METHODS: Seminoma patients with serum hCG levels above normal at first diagnosis were eligible for recruitment. Statistical analysis, including multivariate regression, was performed to identify risk factors. Primary end-points were overall survival (OS) and recurrence-free survival (RFS). RESULTS: We recruited 1031 hCG-positive patients (stage I: n = 586; stage II + III: n = 427) diagnosed between 1981 and 2018. In metastatic disease, LDH levels ≥3 above upper normal limit (UNL) pre- (n = 109) or post-orchiectomy (n = 73) and patients aged ≥40 years (n = 187) were associated with poor prognosis: 5-year OS rates of 84% (LDH ≥3 UNL pre-orchiectomy) versus 92% (<3 UNL pre-orchiectomy) (hazard ratio [HR]: 3.155, [95% confidence interval {CI}: 1.28-7.75], P = 0.012), 82% (≥3 UNL post-orchiectomy) versus 92% (<3 UNL post-orchiectomy) (HR: 6.877, [95% CI: 1.61-29.34]; P = 0.009) and 86% (≥40 years) versus 91% (<40 years) (HR: 6.870, [95% CI: 1.45-13.37], P = 0.009), respectively. A subset of patients with hCG levels ≥2000 IU/l pre-orchiectomy (n = 17) exhibited a poor prognosis, with 5-year OS rates of 73% (≥2000 IU/l) versus 94% (<2000 IU/l) (HR: 3.936, [95% CI: 1.02-12.61], P = 0.047). CONCLUSIONS: Age and LDH levels are significantly associated with poor prognosis in hCG-positive seminoma patients. A small number of patients, with levels of hCG ≥2000 IU/l, may represent a separate prognostic subgroup associated with impaired survival rates.

Active surveillance as a successful management strategy for patients with clinical stage I germ cell testicular cancer.

BACKGROUND: Cancer-specific survival for patients with clinical stage I (CSI) germ cell testicular cancer (GCTC) is outstanding after inguinal orchidectomy regardless the treatment utilized. This study evaluated whether active surveillance (AS) of such patients yielded similar health outcomes to other therapeutic strategies such as adjuvant chemotherapy, radiotherapy or primary retroperitoneal lymphadenectomy as described in the literature. PATIENTS AND METHODS: Patients with CSI GCTC were screened between January 2012 and December 2016. Patients had previously undergone inguinal orchidectomy as the primary treatment and chosen AS as their preferred management strategy after receiving information about all available strategies. RESULTS: Out of 91 patients screened, 82 patients selected AS as their preferred management strategy. Relapse rate in the overall population was 20% (95% CI 12-30) and median time to relapse was 11.5 months (range 1.0-35.0). In patients with seminomatous tumors, relapse rate decreased to 13% and median time to relapse was 13 months; whereas in patients with non-seminomatous tumors, relapse rate was 33% (IA) or 29% (IB) and median time to relapse was 12 months in stage IA and 4.5 months in stage IB patients. All relapses were rescued with three or four cycles of chemotherapy and two also required a retroperitoneal lymphadenectomy. All patients are currently alive and free of disease. CONCLUSIONS: The clinical outcomes of patients with CSI GCTC managed by AS in this series were excellent. This strategy limited the administration of active treatments specifically to the minority of patients who relapsed without compromising performance.

Post-chemotherapy retroperitoneal lymph node dissection in the management of metastatic testis cancer: the 16-year experience in an Irish setting.

INTRODUCTION: Post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) is an important tool in the management of advanced germ cell testis cancer, particularly non-seminoma. AIM: We present the 16-year experience with PC-RPLND in a single Irish tertiary referral centre, and compare our results to the major speciality centres worldwide. METHODOLOGY: All 78 patients undergoing PC-RPLND for the treatment of metastatic testis cancer between January 1996 and December 2011 were included. Medical records were reviewed and up to date follow-up obtained from primary referral centres, patient's GPs and individual patient interview. RESULTS: The mean age at diagnosis was 28.5 ± 7 years. Initial pathology included non-seminoma 62.8 %, seminoma 6.4 % and combined 19.2 %. All patients underwent pre-operative chemotherapy. The resection template utilised was bilateral infra-hilar in 29.5 %, unilateral infra-hilar in 46.2 % and supra-hilar in 20.5 %. Complete abdominal remission was achieved in all but one patient. Additional procedures were required in 38.5 % of patients (n = 30). Clavien Dindo grade three or four complications were seen in 8.9 %, including five patients who required early reoperation. Histology of RPLND specimen showed mature teratoma (41 %) and active cancer (11.5 %). Follow-up data were available for 66 patients (85 %). Median follow-up was 101 (11-207) months. Nine patients relapsed with median time to relapse 15 (8-60) months. Overall 5-year survival rate was 95.2 % (four deaths). CONCLUSION: In this relatively small series due to small population and low disease incidence, we have shown acceptable peri-operative course, morbidity and oncological outcomes with PC-RPLND compared to major international centres.

Germ Cell Cancer and Multiple Relapses: Toxicity and Survival.

PURPOSE: A small number of patients with germ cell cancer (GCC) receive more than one line of treatment for disseminated disease. The purpose of this study was to evaluate late toxicity and survival in an unselected cohort of patients who experienced relapse after receiving first-line treatment for disseminated disease. METHODS: From the Danish Testicular Cancer database, we identified all patients who received more than one line of treatment for disseminated disease. Information about late toxicity and mortality was obtained by means of linkage to national registers. Prognostic factors for relapse and death were identified and compared with the International Prognostic Factors Study Group (IPFSG) classification. RESULTS: In total, 268 patients received more than one line of treatment for disseminated GCC. Approximately half of patients (n=136) died as a result of GCC. The 132 remaining patients, compared with patients treated with only orchiectomy, had an increased risk for a second cancer (hazard ratio [HR], 3.2; 95% CI, 1.9 to 5.5), major cardiovascular disease (HR, 1.9; 95% CI, 1.0 to 3.3), pulmonary disease (HR, 2.0; 95% CI, 1.0 to 3.8), GI disease (HR, 7.3; 95% CI, 3.6 to 14.8), renal impairment (HR, 8.3; 95% CI, 3.0 to 23.2), neurologic disorders (HR, 6.3; 95% CI, 3.1 to 12.6), and death as a result of other causes (HR, 2.6; 95% CI, 1.6 to 4.2). In large part, the IPFSG classification was confirmed in our population; however, we could not confirm the primary site and the level of human chorionic gonadotropin as independent factors. We identified increasing age as a possible new prognostic factor for treatment failure after second-line treatment (HR, 1.2 per 10 years; 95% CI, 1.2 to 15). CONCLUSION: Patients with GCC who survive after more than one line of treatment for disseminated disease have a highly increased risk of late toxicity and death as a result of causes other than GCC. Therefore, they should be candidates for life-long follow-up. The IPFSG classification was confirmed in this unselected population.

Cardiovascular Disease Mortality After Chemotherapy or Surgery for Testicular Nonseminoma: A Population-Based Study.

PURPOSE: Increased risks of incident cardiovascular disease (CVD) in patients with testicular cancer (TC) given chemotherapy in European studies were largely restricted to long-term survivors and included patients from the 1960s. Few population-based investigations have quantified CVD mortality during, shortly after, and for two decades after TC diagnosis in the era of cisplatin-based chemotherapy. PATIENTS AND METHODS: Standardized mortality ratios (SMRs) for CVD and absolute excess risks (AERs; number of excess deaths per 10,000 person-years) were calculated for 15,006 patients with testicular nonseminoma reported to the population-based Surveillance, Epidemiology, and End Results program (1980 to 2010) who initially received chemotherapy (n=6,909) or surgery (n=8,097) without radiotherapy and accrued 60,065 and 81,227 person-years of follow-up, respectively. Multivariable modeling evaluated effects of age, treatment, extent of disease, and other factors on CVD mortality. RESULTS: Significantly increased CVD mortality occurred after chemotherapy (SMR, 1.36; 95% CI, 1.03 to 1.78; n=54) but not surgery (SMR, 0.81; 95% CI, 0.60 to 1.07; n=50). Significant excess deaths after chemotherapy were restricted to the first year after TC diagnosis (SMR, 5.31; AER, 13.90; n=11) and included cerebrovascular disease (SMR, 21.72; AER, 7.43; n=5) and heart disease (SMR, 3.45; AER, 6.64; n=6). In multivariable analyses, increased CVD mortality after chemotherapy was confined to the first year after TC diagnosis (hazard ratio, 4.86; 95% CI, 1.25 to 32.08); distant disease (P<.05) and older age at diagnosis (P<.01) were independent risk factors. CONCLUSION: This is the first population-based study, to our knowledge, to quantify short- and long-term CVD mortality after TC diagnosis. The increased short-term risk of CVD deaths should be further explored in analytic studies that enumerate incident events and can serve to develop comprehensive evidence-based approaches for risk stratification and application of preventive and interventional efforts.

Surveillance for stage I nonseminoma testicular cancer: outcomes and long-term follow-up in a population-based cohort.

PURPOSE: To describe treatment results in a large cohort with stage I nonseminoma germ cell cancer (NSGCC) treated in a surveillance program. PATIENTS AND METHODS: From January 1, 1984, to December 31, 2007, 1,226 patients with stage I NSGCC, including high-risk patients with vascular invasion, were observed in a surveillance program. RESULTS: The relapse rate after orchiectomy alone was 30.6% at 5 years. Presence of vascular invasion together with embryonal carcinoma and rete testis invasion in the testicular primary identified a group with a relapse risk of 50%. Without risk factors, the relapse risk was 12%. Eighty percent of relapses were diagnosed within the first year after orchiectomy. The median time to relapse was 5 months (range, 1 to 308 months). Early relapses were mainly detected by increase in tumor markers, and late relapses were detected by computed tomography scans. Relapses after 5 years were seen in 0.5% of the whole cohort or in 1.6% of relapsing patients. The majority of relapses (94.4%) belonged to the good prognostic group according to the International Germ Cell Cancer Collaborative Group classification. The disease-specific survival at 15 years was 99.1%. CONCLUSION: A surveillance policy for patients with stage I NSGCC is a safe approach associated with an excellent cure rate and an overall low treatment burden despite a high relapse rate in a small group of patients. We recommend surveillance for patients with stage I NSGCC with immediate systemic treatment at relapse. Clearly defined risk factors for relapse are presented if an option of risk-adapted treatment is preferred.

Non-steroidal antiandrogen monotherapy compared with luteinising hormone-releasing hormone agonists or surgical castration monotherapy for advanced prostate cancer.

BACKGROUND: Non-steroidal antiandrogens and castration are the main therapy options for advanced stages of prostate cancer. However, debate regarding the value of these treatment options continues. OBJECTIVES: To assess the effects of non-steroidal antiandrogen monotherapy compared with luteinising hormone-releasing hormone agonists or surgical castration monotherapy for treating advanced stages of prostate cancer. SEARCH METHODS: We searched the Cochrane Prostatic Diseases and Urologic Cancers Group Specialized Register (PROSTATE), the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Web of Science with Conference Proceedings, three trial registries and abstracts from three major conferences to 23 December 2013, together with reference lists, and contacted selected experts in the field and manufacturers. SELECTION CRITERIA: We included randomised controlled trials comparing non-steroidal antiandrogen monotherapy with medical or surgical castration monotherapy for men in advanced stages of prostate cancer. DATA COLLECTION AND ANALYSIS: One review author screened all titles and abstracts; only citations that were clearly irrelevant were excluded at this stage. Then, two review authors independently examined full-text reports, identified relevant studies, assessed the eligibility of studies for inclusion, assessed trial quality and extracted data. We contacted the study authors to request additional information. We used Review Manager 5 for data synthesis and used the fixed-effect model for heterogeneity less than 50%; we used the random-effects model for substantial or considerable heterogeneity. MAIN RESULTS: Eleven studies involving 3060 randomly assigned participants were included in this review. The quality of evidence is hampered by risk of bias. Use of non-steroidal antiandrogens decreased overall survival (hazard ratio (HR) 1.24, 95% confidence interval (CI) 1.05 to 1.48, six studies, 2712 participants) and increased clinical progression (one year: risk ratio (RR) 1.25, 95% CI 1.08 to 1.45, five studies, 2067 participants; 70 weeks: RR 1.26, 95% CI 1.08 to 1.45, six studies, 2373 participants; two years: RR 1.14, 95% CI 1.04 to 1.25, three studies, 1336 participants), as well as treatment failure (one year: RR 1.19, 95% CI 1.02 to 1.38, four studies, 1539 participants; 70 weeks: RR 1.27, 95% CI 1.05 to 1.52, five studies, 1845 participants; two years: RR 1.14, 95% CI 1.05 to 1.24, two studies, 808 participants), compared with medical or surgical castration. The quality of evidence for overall survival, clinical progression and treatment failure was rated as moderate according to GRADE. Predefined subgroup analyses showed that use of non-steroidal antiandrogens, compared with castration, was less favourable for overall survival, clinical progression (at one year, 70 weeks, two years) and treatment failure (at one year, 70 weeks, two years) in men with metastatic disease. Use of non-steroidal antiandrogens also increased the risk for treatment discontinuation due to adverse events (RR 1.82, 95% CI 1.13 to 2.94, eight studies, 1559 participants), including events such as breast pain (RR 22.97, 95% CI 14.79 to 35.67, eight studies, 2670 participants), gynaecomastia (RR 8.43, 95% CI 3.19 to 22.28, nine studies, 2774 participants) and asthenia (RR 1.77, 95% CI 1.36 to 2.31, five studies, 2073 participants). The risk of other adverse events, such as hot flashes (RR 0.23, 95% CI 0.19 to 0.27, nine studies, 2774 participants), haemorrhage (RR 0.07, 95% CI 0.01 to 0.54, two studies, 546 participants), nocturia (RR 0.38, 95% CI 0.20 to 0.69, one study, 480 participants), fatigue (RR 0.52, 95% CI 0.31 to 0.88, one study, 51 participants), loss of sexual interest (RR 0.50, 95% CI 0.30 to 0.83, one study, 51 participants) and urinary frequency (RR 0.22, 95% CI 0.11 to 0.47, one study, 480 participants) was decreased when non-steroidal antiandrogens were used. The quality of evidence for breast pain, gynaecomastia and hot flashes was rated as moderate according to GRADE. The effects of non-steroidal antiandrogens on cancer-specific survival and biochemical progression remained unclear. AUTHORS' CONCLUSIONS: Currently available evidence suggests that use of non-steroidal antiandrogen monotherapy compared with medical or surgical castration monotherapy for advanced prostate cancer is less effective in terms of overall survival, clinical progression, treatment failure and treatment discontinuation due to adverse events. Evidence quality was rated as moderate according to GRADE. Further research is likely to have an important impact on results for patients with advanced but non-metastatic prostate cancer treated with non-steroidal antiandrogen monotherapy. However, we believe that research is likely not necessary on non-steroidal antiandrogen monotherapy for men with metastatic prostate cancer. Only high-quality, randomised controlled trials with long-term follow-up should be conducted. If further research is planned to investigate biochemical progression, studies with standardised follow-up schedules using measurements of prostate-specific antigen based on current guidelines should be conducted.

Differences in time to disease progression do not predict for cancer-specific survival in patients receiving immediate or deferred androgen-deprivation therapy for prostate cancer: final results of EORTC randomized trial 30891 with 12 years of follow-up.

BACKGROUND: Trials assessing the benefit of immediate androgen-deprivation therapy (ADT) for treating prostate cancer (PCa) have often done so based on differences in detectable prostate-specific antigen (PSA) relapse or metastatic disease rates at a specific time after randomization. OBJECTIVE: Based on the long-term results of European Organization for Research and Treatment of Cancer (EORTC) trial 30891, we questioned if differences in time to progression predict for survival differences. DESIGN, SETTING, AND PARTICIPANTS: EORTC trial 30891 compared immediate ADT (n=492) with orchiectomy or luteinizing hormone-releasing hormone analog with deferred ADT (n=493) initiated upon symptomatic disease progression or life-threatening complications in randomly assigned T0-4 N0-2 M0 PCa patients. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Time to first objective progression (documented metastases, ureteric obstruction, not PSA rise) and time to objective castration-resistant progressive disease were compared as well as PCa mortality and overall survival. RESULTS AND LIMITATIONS: After a median of 12.8 yr, 769 of the 985 patients had died (78%), 269 of PCa (27%). For patients receiving deferred ADT, the overall treatment time was 31% of that for patients on immediate ADT. Deferred ADT was significantly worse than immediate ADT for time to first objective disease progression (p<0.0001; 10-yr progression rates 42% vs 30%). However, time to objective castration-resistant disease after deferred ADT did not differ significantly (p=0.42) from that after immediate ADT. In addition, PCa mortality did not differ significantly, except in patients with aggressive PCa resulting in death within 3-5 yr after diagnosis. Deferred ADT was inferior to immediate ADT in terms of overall survival (hazard ratio: 1.21; 95% confidence interval, 1.05-1.39; p [noninferiority]=0.72, p [difference] = 0.0085). CONCLUSIONS: This study shows that if hormonal manipulation is used at different times during the disease course, differences in time to first disease progression cannot predict differences in disease-specific survival. A deferred ADT policy may substantially reduce the time on treatment, but it is not suitable for patients with rapidly progressing disease.

Oncological outcomes in patients with stage I testicular seminoma and nonseminoma: pathological risk factors for relapse and feasibility of surveillance after orchiectomy.

BACKGROUND: Surveillance after orchiectomy has recently been a management option in patients with stage I seminoma, while it remains controversial in those with stage I nonseminoma, and the risk factor associated with relapse is still a matter of concern in both entities. This study was performed to explore pathological risk factors for post-orchiectomy relapse in patients with stage I seminoma and nonseminoma, and to assess oncological outcomes in those managed with surveillance. METHODS: In this single institution study, 118 and 40 consecutive patients with stage I seminoma and nonseminoma were reviewed, respectively. Of the 118 patients with stage I seminoma, 56 and one received adjuvant radiotherapy and chemotherapy, respectively, and 61 were managed with surveillance. Of the 40 men with stage I nonseminoma, 4 underwent adjuvant chemotherapy and 36 were managed with surveillance. RESULTS: No patient had cause-specific death during the mean observation period of 104 and 99 months in men with seminoma and nonseminoma, respectively. In men with stage I seminoma, 1 (1.7%) receiving radiotherapy and 4 (6.6%) men managed with surveillance had disease relapse; the 10-year relapse-free survival (RFS) rate was 93.4% in men managed with surveillance, and their RFS was not different from that in patients receiving adjuvant radiotherapy (log rank P=0.15). Patients with tunica albuginea involvement showed a poorer RFS than those without (10-year RFS rate 80.0% vs. 94.1%), although the difference was of borderline significance (P=0.09). In men with stage I nonseminoma, 9 (22.5%) patients experienced relapse. Patients with lymphovascular invasion seemingly had a poorer RFS than those without; 40.0% and 18.7% of the patients with and without lymphovascular invasion had disease relapse, respectively, although the difference was not significant (log rank P=0.17). CONCLUSION: In both men with stage I seminoma and nonseminoma, surveillance after orchiectomy is a feasible option. However, disease extension through tunica albuginea might be a factor associated with disease relapse in patients with organ-confined seminoma, and those with stage I nonseminoma showing lymphovascular invasion may possibly be at high risk for disease relapse.

Coelioscopic orchiectomy can be effectively and safely accomplished in chelonians.

Coelioscopic orchiectomy was performed in 27 male turtles (25 juvenile to adult red-eared sliders (Trachemys scripta elegans), one adult eastern painted turtle (Chrysems picta picta), and one juvenile male yellow-spotted Amazon River turtle (Podocnemis unifilis)). Orchiectomy was conducted under coelioscopic visualisation using ligation and transection of the mesorchium, or transection of the mesorchium with monopolar radiosurgical scissors. In 22 cases, bilateral orchiectomy was performed through a single incision; five turtles required bilateral incisions. All turtles recovered from anaesthesia. Nine turtles died within one year of surgery from conditions believed to be unrelated to surgery. One turtle was lost to follow-up. Seventeen turtles remain clinically healthy one to three years postoperatively. Coelioscopic orchiectomy provides a minimally invasive method for sterilisation of male chelonians and provides excellent visualisation during surgery. This technique is a useful model for the development of additional minimally invasive surgical techniques for chelonians.

Periostin expression correlates with pT-stage, grading and tumour size, and independently predicts cancer-specific survival in surgically treated penile squamous cell carcinomas.

AIMS: Overexpression of periostin, a secreted cell adhesion molecule, has been reported to enhance invasion and angiogenesis in squamous cell carcinomas (SCCs) derived from different anatomic sites. We studied the so far neglected periostin expression profiles in penile SCCs and evaluated its association with pertinent clinicopathologic variables. METHODS: Paraffin-embedded tissues from 89 patients with surgically treated penile SCCs were subjected to a central histopathologic review performed by one pathologist. Then, tissue microarray technique was employed for periostin immunostaining which was evaluated by two independent raters. Kappa (κ)-statistics were used to assess interobserver variability. Spearman correlations as well as uni- and multivariable Cox proportional hazards analysis were applied to assess the association between periostin expression and clinicopathologic parameters. Mean postsurgical follow-up was 31.5 months (IQR 6-66). RESULTS: Periostin expression was recorded in 39/89 penile SCCs (44%). K-statistics disclosed substantial interobserver agreement for epithelial and stromal staining evaluation (K-values 0.76 vs 0.83, p values <0.001). High periostin expression in either stroma or tumour epithelia showed a significant positive correlation with tumour size, histologic grade and pT-stage. In the multivariable Cox models including pT-stage, pN status, grading and the patients' age at the time of surgery, periostin expression independently predicted cancer-specific survival (CSS). CONCLUSIONS: Immunohistochemically, periostin is not infrequently expressed in penile cancer, and might become a valuable tool to independently predict CSS after surgical treatment. Further studies should clarify the so far unresolved usefulness of periostin to be employed as a possible molecular target in antineoplastic therapy in metastasised penile SCCs.

First-line treatment of metastatic prostate cancer. Androgen suppression for symptomatic disease.

Prostate cancer sometimes metastasizes, especially to bone, which may cause pain, fractures and spinal cord compression. What are the best first-line treatment options for patients with metastatic prostate cancer? To answer this question, we conducted a review of the literature, using the standard Prescrire methodology. Suppressing androgen secretion by surgically removing the testicles (orchiectomy) or by administering a gonadorelin agonist relieves the pain associated with bone metastases in about 80% of patients. This treatment has a clear impact on symptoms, despite the lack of clinical trials versus placebo or no treatment. Its impact on overall survival is uncertain. In terms of survival, goserelin therapy appears to have similar efficacy to orchiectomy. The efficacy of other gonadorelin agonists is less well documented. Degarelix, a gonadorelin antagonist, does not appear to provide a therapeutic advantage over gonadorelin agonist. In 2012, oestrogen should not be used in the treatment of metastatic prostate cancer, because of its cardiovascular adverse effects. Antiandrogen monotherapy, preferably with flutamide, appears to be less beneficial than orchiectomy in terms of survival. Overall, adverse effects are more frequent with nonsteroidal antiandrogens than with gonadorelin agonists, but sexual dysfunction is less frequent. Cyproterone, a steroidal antiandrogen, seems to have fewer adverse effects leading to treatment discontinuation than nonsteroidal antiandrogens. There is no firm evidence that starting hormonal therapy before metastases become symptomatic is beneficial. When symptoms have disappeared and the PSA level is low, one option is to temporarily interrupt gonadorelin agonist therapy if it is poorly tolerated, even though this may shorten survival by a few months. The addition of a nonsteroidal antiandrogen to androgen suppression therapy slightly improves 5-year survival, preventing about 3 deaths per 100 patients, but at a cost of additional adverse effects. First-line hormonal treatments are initially very effective in relieving symptoms of metastatic prostate cancer. Our analysis of the available data suggests that the best treatment option is androgen suppression with goserelin. Flutamide monotherapy is an alternative for some patients.

Late relapses (>2 years) in patients with stage I testicular germ cell tumors: predictive factors and survival.

OBJECTIVES: Late relapses (>2 years) after completion of chemotherapy are rare and often platinum-resistant. There are limited data concerning late relapses in chemotherapy-naïve patients with stage I germ cell tumors. This retrospective analysis was performed to compare the outcome between patients with stage I germ cell tumors, who had late (≥2 years) and early (≥3 months and <2 years) relapse after orchiectomy. METHODS AND MATERIALS: We analyzed data of 1,069 chemotherapy-naïve patients with advanced germ cell tumors of testis treated in our department from 1986 to 2008. All patients had cisplatin- and etoposide-based chemotherapy. We identified 169 (15.8%) patients with prior stage I disease, who had not received adjuvant treatment: 140 and 29 patients had early and late relapse, respectively. Among patients with late relapse, pure seminoma was revealed in 14 patients, and nonseminoma in 15 patients. Median follow-up time for 169 patients was 35 (range, 2-218) months. RESULTS: Patients with late relapse were older, 35 years (23-57) and had more frequent pure seminoma in primary tumor, 14/29 (48.3%), than patients with early relapse, 30 years (16-63) (P = 0.0008) and 46/140 (32,8%, P = 0.08), respectively. At the time of disease progression, both groups were very similar according to well-known prognostic factors including IGCCCG classification. The only difference was larger size of retroperitoneal lymph nodes in late (9 cm) than in early relapse (4 cm, P < 0.0001). The outcome in patients with late relapse was significantly worse than in patients with early relapse: complete response rate after induction chemotherapy was 20.7% (6/29) vs. 42.1% (59/140) (P = 0.01), 3-year progression-free survival 66% vs. 84% (P = 0.02, HR = 2.4, 95% CI 1.2-8.8) and 3-year overall survival, 72% vs. 88% (P = 0.04, HR = 2.4, 95% CI 1.05-10.25), respectively. In patients with pure seminoma, this difference in overall survival was even more significant: 65% vs. 91% (P = 0.04, HR = 3.8, 95% CI 1.06-32.4). CONCLUSIONS: Late relapses following stage I germ cell tumors were associated with seminoma, older age, and worse outcome after induction chemotherapy.

Characterising the castration-resistant prostate cancer population: a systematic review.

BACKGROUND: Castration-resistant prostate cancer (CRPC) is an advanced form of prostate cancer associated with poor survival rates. However, characterisation of the disease epidemiology is hampered by use of varying terminology, definition and disease management. The aim of this review was to conduct a systematic review to provide greater clarity on the sum of the available epidemiologic evidence and to guide future research into the disease prevalence, progression, characteristics and outcome. METHODS: Systematic searches of PubMed and Embase were performed in March 2010 to identify relevant observational studies relating to the epidemiology, progression and outcomes of CRPC. Further studies were identified for inclusion in our review through manual searches of the authors' bibliographical databases and the reference lists of the included articles. RESULTS: We identified 12 articles (10 full papers and 2 abstracts) reporting studies that included a total of 71,179 patients observed for up to 12 years for evaluation in our review. Five studies looked at the prevalence of CRPC in patients with prostate cancer. Together, the data indicate that 10-20% of prostate cancer patients develop CRPC within approximately 5 years of follow-up. Two studies reported the prevalence of bone metastases present at diagnosis of CRPC. Together, ≥ 84% were shown to have metastases at diagnosis. Of those patients with no metastases present at diagnosis of CRPC, 33% could expect to develop them within 2 years. The median survival of patients with CRPC was reported in five studies, with values varying from 9 to 30 months. A pooled, sample-weighted survival estimate calculated from the survival data included in this review is 14 months. Very few studies that met our inclusion criteria evaluated treatment patterns in CRPC. One study reported that only 37% of patients with CRPC received chemotherapy, with the remainder receiving only steroids and supportive care. The most common palliative therapies administered to patients with skeletal symptoms were radiotherapy, radionuclide therapy, bisphosphonates and opioids. CONCLUSIONS: This review highlights the poor prognosis of patients with CRPC, and demonstrates a survival of 9-13 months in those patients with metastatic CRPC. Furthermore, progression to CRPC is associated with deterioration in quality of life, and few therapeutic options are currently available to patients with CRPC. However, epidemiologic study of these patients is hampered by differing terminology, definitions and treatment paradigms. Our review highlights the need for further well-designed, epidemiological studies of CRPC, using standardised definitions and methods.

Surveillance in stage I seminoma patients: a long-term assessment.

BACKGROUND: Following orchidectomy patients with stage I seminoma of the testis may be managed by either surveillance or adjuvant treatment. In view of the very high cure rate, it is important to analyse long-term outcomes. OBJECTIVE: To provide data to advise patients on treatment burden and risk of recurrence associated with surveillance. DESIGN, SETTING, AND PARTICIPANTS: We audited the case records of 164 stage I seminoma patients registered at the Royal Marsden Hospital who were managed with a surveillance policy between 1980 and 2004 and followed for 1-20 yr (median: 13.5 yr). MEASUREMENTS: All treatments and patterns of relapse were documented. RESULTS AND LIMITATIONS: Twenty-two of 164 (13%) patients had relapsed at a median of 15.5 mo (range: 6-55 mo) from orchidectomy. Eighteen relapses appeared to be confined to the para-aortic nodes, but 6 of the 13 (46%) men treated with only para-aortic radiotherapy suffered a further relapse at another site. The disease-specific mortality was 1.3%. In the complete series of 164 patients, a total of 50 cycles of chemotherapy and 26 courses of radiotherapy was administered, representing an average of 0.46 "treatment units" per patient or an average of 3.45 treatment units per relapsing patient. The total number of treatment days was 390 d for radiotherapy and 133 d for chemotherapy, representing an average of 3.2 d per patient or 23.8 d per relapsing patient. This was a single-centre series extending back to the 1980s. Imaging and treatment protocols have advanced since then. CONCLUSIONS: Surveillance postorchidectomy is a safe practice in the long term, and the majority of patients can avoid further treatment. There is the risk that those who do relapse face a higher burden of treatment than would be required if adjuvant treatment had been given.

Effect of post-natal castration on sepsis mortality in rats.

PURPOSE: To investigate the influence of castration in early periods of development on survival to experimental acute sepsis. METHODS: Four groups of 10 (ten) Wistar rats were used. The groups were comprised of males (M), females (F), males castrated on the fourth day of life (CM) and males castrated on the fourth day of life with testosterone replacement (CMR). Sepsis was induced by ligature and cecal perforation in adult life. RESULTS: The analysis of death within 24 hours following sepsis induction showed greater mortality between the M and the CMR groups as compared to the CM and F (p=0.0180) groups. Multiple correspondence analysis (MCA) indicates an association between the M and the CMR groups for death within 24 hours as well as a relationship between the F and the CM groups for the absence of death and death up to 24 hours following sepsis induction. Statistical analysis of the Kaplan-Meier survival curve through log-rank demonstrates a significant difference among the four groups (p=0.0055) and between the M and the F (p=0.0005) groups. CONCLUSION: Data suggest a better survival to sepsis within 24 hours for the F and CM groups, the presence or absence of testosterone in early periods of post-natal life being responsible for these findings.

Gender identity disorder. Is this a potentially fatal condition?

A person with a Gender Identity Disorder (GID) is a person who strongly identifies with the other sex. The individual may identify with the opposite sex to the point of believing that he/she is, in fact, a member of the other sex who is trapped in the wrong body. The treatment option is sex reassignment surgery. In Pakistan There is no specialized facility sex reassignment surgery. This case report deals with possible serious outcome of GID in Pakistan as a result of castration procedure which is carried out by 'gurus' in Pakistan. A systemic research in our country to this effect is required to find out the outcome of GID in Pakistan.

Costs and complications of equine castration: a UK practice-based study comparing 'standing nonsutured' and 'recumbent sutured' techniques.

REASONS FOR PERFORMING STUDY: Clinicians are often asked to guide owners and trainers over the relative advantages and disadvantages of equine castration performed in either the standing horse with an open unsutured scrotal wound with healing by second intention, or a recumbent horse under general anaesthesia in aseptic conditions, with sutured scrotal skin allowing primary wound closure. OBJECTIVES: To identify types and frequency of complications following the 2 differing approaches, and to compare the financial cost associated with each procedure, based on practice charges. METHODS: Veterinary expenses of 217 horses castrated by a Newmarket equine veterinary practice over an 18-month period were analysed. Of these, Group 1 (n = 121) were castrated standing and nonsutured by one of 2 ambulatory clinicians and Group 2 (n = 96) castrated in recumbency, in aseptic equine hospital conditions. RESULTS: Group 1 had a complication prevalence of 22% with no mortalities, and Group 2 a significantly lower complication prevalence of 6% (P = 0.001) with a mortality rate of 1%. The financial cost of Group 1, without complications, was approximately one-third of the cost of uncomplicated Group 2. However, the cost of Group 1 with complications increased to approximately two-thirds of the cost of an uncomplicated Group 2 castration. CONCLUSIONS: Even though the complication prevalence for Group 1 castrations leaving an open scrotal wound was significantly higher than for a recumbent horse with a sutured scrotal wound in a hospital, the average cost of Group 1 was still less, even taking into account the additional follow-up costs associated with treating such complications. POTENTIAL RELEVANCE: This report provides a benchmark for the outcome of 2 methods of castration based on a database obtained from particular circumstances within the practice involved. Further studies are required to corroborate and take into account future development in surgical and anaesthetic techniques.