Finding of no tumor (pT0) in patients undergoing radical retropubic prostatectomy for clinically localized prostate cancer

OBJECTIVE: To evaluate features and clinical outcome of patients with clinically localized prostate cancer graded pT0 following radical retropubic prostatectomy (RRP). STUDY DESIGN: Between 1974 and 2001 we performed 1,135 RRPs for cT1-T2 prostate cancer, of which 386 (34%) underwent 3-6 months of neoadjuvant endocrine treatment (NHT) before RRP. Median clinical follow-up was 53.8 months (range 24-251). Estimation of likelihood events for biochemical relapse was calculated according to the Kaplan-Meier method. Statistical differences between curves were calculated using the log-rank test. RESULTS: In 24 cases (2.12%) routine histologic workup failed to detect residual tumor. The pT0 group contained a higher proportion of cTla-b patients and a biopsy Gleason score < or =6. A tendency toward lower pre-operatory PSA levels in the pT0 group compared to the pT2-3 group was shown. PSA progression was observed in 3 pT0 patients, all of whom previously underwent NHT. CONCLUSION: Patients pT0 at RRP presented with lower preoperative PSA values and low preoperative Gleason score compared to the pT+ group. Absence of tumor at pathology examination has a different clinical meaning when it occurs following NHT or in untreated patients. Patients pT0 after NHT may have a worse clinical outcome than pT0 untreated patients.     

Selecting treatment for high-risk, localized prostate cancer: the case for radical prostatectomy

The most common treatment options for men with clinically localized prostate cancer include radical prostatectomy and radiation therapy. The choice between these options is often controversial, and selecting the optimal treatment poses a great challenge for patients and physicians. Factors important to the decision include age and life expectancy of the patient, the natural history of the prostate cancer, how curable the disease is, and the morbidity of treatment. Use of these criteria to select treatment for a healthy, 70-year-old man presenting with a nonpalpable tumor, stage T1c disease, serum prostate-specific antigen of 12 ng/mL, and an adenocarcinoma with a Gleason score of 8 that is present in 2 of 12 biopsy cores would lead to the choice of radical prostatectomy over radiation therapy. Data show that such a patient has a life expectancy of more than 12.3 years if the prostate cancer can be cured and a high probability of dying from the disease if it is not cured. Data further show that radical prostatectomy in such a patient would confer a survival advantage over radiation therapy without resulting in greater complications or reduction in quality of life.     

Dynamic thiol/disulphide homeostasis before and after radical prostatectomy in patients with prostate cancer

Abstract

Thiol groups are important anti-oxidants and essential molecules protecting organism against the harmful effects of reactive oxygen species (ROS). The aim of our study is to evaluate thiol–disulphide homeostasis with a novel recent automated method in patients with localized prostate cancer (PC) before and six months after radical prostatectomy (RP). 18 patients with PC and 17 healthy control subjects were enrolled into the study. Blood samples were collected from the controls subjects and patients before and six months after RP. Thiol–disulphide homeostasis was determined using a recently developed novel method. Prostate-specific antigen (PSA), albumin, total protein, total thiol, native thiol, disulphide and total antioxidant status (TAS) were measured and compared between the groups. Native thiol, total thiol and TAS levels were significantly higher in the control group than the patients before RP (p?<?.001). There was a non-significant increase in the native thiol, total thiol and TAS levels in the patients six months after RP in comparison to the levels before RP (p values .3, .3 and .09, respectively). We found a significant negative correlation between PSA and thiol levels. Our study demonstrated that the decreased thiol and TAS levels weakened anti-oxidant defence mechanism in the patients with PC as indicated. Increased oxidative stress in prostate cancer patients may cause metabolic disturbance and have a role in the aetiopathogenesis of prostate cancer.     

A multi-institutional pilot study of adjuvant docetaxel for patients with prostate cancer at high risk for relapse after radical prostatectomy

The management of patients with high-risk, early-stage, prostate cancer represents a major challenge to all disciplines involved in the treatment of this common malignant neoplasm. A definition of the natural history of this disease-including the identification of key prognostic factors-and the availability of active systemic therapeutic modalities for patients with advanced disease are among the basic requirements needed to provide for early intervention in high-risk patients. Several cytotoxic chemotherapy regimens have demonstrated significant antitumor effects in patients with hormone-refractory disease. Docetaxel (Taxotere(R), Aventis Pharmaceuticals, Bridgewater, NJ), a widely used taxane with broad antitumor activity, likely represents the most active single agent in prostate cancer treatment. Current data indicate that 40%-60% of patients treated with docetaxel have exhibited evidence of benefit from treatment with docetaxel, both alone and in combination with estramustine, with acceptable toxicity. In this review we describe a pilot study that is currently entering patients at high risk for relapse after radical prostatectomy. This study was designed to evaluate the safety, feasibility, and preliminary efficacy of docetaxel given postoperatively for 6 months. The main study endpoint is time-to-biochemical-relapse, which will be assessed against a matched group of historical controls.     

Biochemical failure and toxicity in treatment with brachytherapy and external beam radiotherapy compared with radical prostatectomy in localized prostate cancer

BackgroundLocalized prostate cancer (T1–3N0M0) has therapeutic options such as radical prostatectomy (RP), external beam radiation therapy (EBRT) and brachytherapy (BT). However, the evidence of the outcome of these treatments is limited and no studies have been conducted comparing biochemical failure (BF) and toxicity associated with surgical treatment and EBRT + high-dose brachytherapy (HDBT) in the region.Materials and methodsRetrospective cohort study, clinical records of patients diagnosed with localized prostate cancer between 2014 and 2018 were reviewed at one of the main private neoplasm centers in Lima, Peru; Cox regression was used for both the BF outcome and the grade 2 toxicity outcome, calculating the hazard ratio (HR) with 95% confodence interval (CI).ResultsOf 549 patients, 76.3% (419) received RP as primary treatment, and 72% were between 50 and 70 years old at the time of diagnosis. The patients treated with EBRT + HDBT presented worse characteristics. The EBRT + HDBT group had a 40% lower risk of presenting BF (HR = 0.6; 95% CI: 0.4–0.9), and also a 50% greater risk of presenting toxicity greater than or equal to grade 2 (HR = 1.5; 95% CI: 1.0–2.0) than the group treated with RP.ConclusionOur results show that when comparing patients treated with EBRT + HDBT and RP, BF was greater in RP, and post-treatment toxicity was greater in EBRT + HDBT.     

Evaluation of 18F-PSMA-1007 PET/CT in prostate cancer patients with biochemical recurrence after radical prostatectomy

PurposeProstate-specific membrane antigen (PSMA) ligands targeting has shown promising results in staging of prostate cancer (PCa). The aim of present study was to evaluate the value of ¹⁸F-PSMA-1007 PET/CT in PCa patients with biochemical recurrence.Methods71 patients with PCa after radical prostatectomy (RP) were included in the present study. Median prostate-specific antigen (PSA) level was 1.27 ng/mL (range 0.01–67.40 ng/mL, n = 69). All patients underwent whole-body PET/CT imaging after injection of 333±38 MBq ¹⁸F-PSMA-1007. The distribution of PSMA-positive lesions was assessed. The influence of PSA level, androgen deprivation therapy and primary Gleason score on PSMA-positive finding and uptake of ¹⁸F-PSMA-1007 were evaluated.Results56 (79%) patients showed at least one pathological finding on ¹⁸F-PSMA-1007 PET/CT. The rates of positive scans were 50%, 80%, 100%, 100% among patients with PSA levels ≤0.5, 0.51–1.0, 1.1–2.0 and >2.0 ng/mL, respectively. The median Gleason score was 8 (range 7–10), and higher Gleason score (≤7 vs. ≥8) leads to higher detection rates (58.3% (14/24) vs. 88.9% (32/36), P = 0.006). The median SUVmax of positive findings in patients with PSA levels ≤0.5, 0.51–1.0, 1.1–2.0 and >2.0 ng/mL were 4.51, 4.27, 11.50 and 14.08, respectively. The median SUVmax in patients with PSA level >2.0 ng/mL was significantly higher than that in patients with PSA ≤2.0 ng/mL (14.08 vs. 6.13, P<0.001).Conclusion¹⁸F-PSMA-1007 PET/CT demonstrated a high detection rate for patients with a raised PSA level after radical prostatectomy even in patients with extremely low PSA level (eg. PSA level ≤0.5 ng/mL), which was essential for further clinical management for PCa patients.     

Treatment outcomes and late toxicities of intensity-modulated radiation therapy for 1091 Japanese patients with localized prostate cancer

Aim

This study aimed to evaluate the treatment result of intensity-modulated radiation therapy (IMRT) in a large number of Japanese patients with prostate cancer.

Migrations in clinical and pathological stage of prostatic carcinoma in patients undergoing radical prostatectomy in the period between 1993 and 2003

The aim of this study based on an analysis of personal material was to establish stage migration in a relatively large number of patients who had undergone radical retropubic ascendant prostatectomy (RRP). Between 01.07.1993. and 31.06.2003. RRP was performed in 801 patients at the urology department of the Kliniken-Essen-Mitte. Data regarding diagnostic workup, treatment and postoperative course were collected prospectively into a database. An analysis was made regarding clinical and pathological stage and numbers of patients with positive lymph nodes. During the observation period the number of radical prostatectomies increased significantly from 8 in 1993 to 130 in 2002. The number of organ-confined tumors increased continuously between 1997 and 2003. In contrast to this, advanced and metastatic tumors showed a continuous decrease from 76% in 1997 to 66% in 2002. Between 1994 and 2003 the number of T1c tumors increased by 20%. Introduction of systematic 12-cylinder biopsy (S12C) increased the detection of prostatic carcinoma by 38% and the number of diagnosed tumors of a lower clinical stage increased. These facts confirm a trend towards clinical and pathological stage migration resulting from extensive use of prostate specific antigen (PSA) and S12C biopsy in the diagnosis of prostatic carcinoma.     

Evaluation and treatment of men with biochemical prostate-specific antigen recurrence following definitive therapy for clinically localized prostate cancer

Early detection and monitoring by serum prostate-specific antigen (PSA) measurement has increased the number of men presenting with potentially curable prostate cancer. Most will choose radical prostatectomy or some form of radiation therapy for treatment, but some will have evidence of biochemical disease recurrence following therapy, shown by a rising PSA level without other clinical evidence of disease. Radical prostatectomy involves the removal of all prostate tissue, causing the serum PSA to decline to undetectable levels within four to six weeks following surgery; a subsequent rise in the serum PSA to a detectable level indicates disease recurrence. Patients should be evaluated to assess whether rising PSA levels indicate local recurrence or early metastatic disease. The advantages of salvage radiation, endocrine therapy, and other treatment modalities in local disease recurrence must be weighed against potential side effects and the resulting decrease in quality of life. Radiation therapy does not immediately eradicate all PSA-producing cells; therefore the persistence of a detectable PSA does not necessarily imply residual cancer, but rising PSA levels indicate treatment failure. Salvage surgery can be performed after radiotherapy for the purpose of removing all viable cancer cells, but should be weighed against a higher incidence of surgical complications; cryoablation offers a less invasive therapeutic modality.     

Value of percent free prostate-specific antigen for the prediction of pathological stage in men with clinically localized prostate cancer

PURPOSE: To analyze if the percentage of free prostate-specific antigen (PSA) can provide additional information to the combination of local clinical stage, serum PSA and Gleason score in the prediction of final stage and pathological features of prostate cancer. MATERIALS AND METHODS: A group of 480 men with clinically localized prostate cancer underwent lymphadenectomy and radical prostatectomy. Total and free PSA were measured in preoperative serum. Clinical stage was T1 in 70.4% of patients and T2 in 29.6%. The biopsy Gleason score ranged between 2 and 4 in 5.6%, between 5 and 7 in 78.4%, and was higher than 7 in 16%. Total serum PSA was below 4.1 ng/mL in 4.3%, between 4.1 and 10 ng/mL in 66.4%, between 10.1 and 20 ng/mL in 22.5%, and higher than 20 in 6.7% of patients. The tumor was organ-confined in 49.8% and specimen-confined in 64.2%, and its pathological features were favorable in 35%. RESULTS: Multiple logistic regression analysis demonstrated that percent free PSA has independent predictive value for pathological stage only in the subset of patients with cT1 tumors and serum PSA between 4.1 and 10 ng/mL. In this group the probability of organ-confined cancer was 68.3% if the percent free PSA was above 15 and 56.3% if it was lower (p<0.001). The probability of specimen-confined disease was 86.6% and 71.3%, respectively (p<0.007), and the probability of favorable pathology was 59.8% and 39.6%, respectively (p<0.002). We also found higher rates of organ- and specimen-confined tumors and favorable pathology for every Gleason score when the percent free PSA was higher than 15. CONCLUSIONS: Percent free PSA seems to provide additional information to the combination of clinical stage and Gleason score for the prediction of pathological features only in patients with clinical stage T1c and serum PSA between 4.1 and 10 ng/mL.     

Localization of annexins I, II, IV and VII in whole prostate sections from radical prostatectomy patients

Annexins (ANXs) represent a family of calcium and phospholipid binding proteins that are involved in several physiological processes e.g. signal transduction, cellular differentiation and proliferation. Since they are known to be dysregulated in a variety of cancers we investigated the immunolocalization of ANXs in whole prostate sections containing benign prostatic epithelium (BPE), benign prostatic hyperplasia (BPH), prostatic intraepithelial neoplasia (PIN) and prostate cancer (PCa) in order to evaluate their possible role during tumorigenesis. Samples were obtained from 28 patients undergoing radical prostatectomy. Gross sections of whole prostates were examined immunohistochemically for the distribution of ANX I, II, IV and VII. In BPE all ANXs were localized to the cell membranes and the cytoplasm of all gland cells. In BPH the immunoreactivity of ANX I and II was restricted to the basal cells of glands and expression pattern of ANX IV and VII was similar to BPE. In PIN only basal cells expressed ANX II. In PCa ANX II immunoreactivity was absent and weak ANX I and ANX IV immunoreactivity was restricted to the cytoplasm of tumor cells. ANX VII immunoreactivity was seen in some but not all tumor cells. Since ANX IV and VII expression did not show significant changes in PCa compared to non-neoplastic tissue and PIN an essential role during prostate tumourigenesis seems unlikely. In contrast, as progression from PIN to PCa is characterized by a reduction of ANX I and II this suggests that downregulation of these proteins could represent an important event in prostate carcinogenesis.     

Temporal trends in the surgical outcomes of patients with breast cancer

ABSTRACT: BACKGROUND: The incidence of breast cancer has been increasing in Japan over the past three decades, and it is the currently the most common malignancy in Japan. This study investigated the temporal trends of the surgical outcomes in patients with breast cancer. METHODS: We evaluated 543 consecutive patients who underwent breast-cancer resection between 1980 and 2009. The temporal trends in the surgical outcome and clinicopathological features were evaluated separately for the periods covering 1980 to 1989, 1990 to 1999, and 2000 to 2009. RESULTS: The number of patients who underwent resection during these three respective periods were 133, 176, and 234, respectively. All patients were women. The percentage of patients at stages 0 or 1 was 63.2%, 58.5%, and 43.6%, respectively, during the three periods. The mean diameter of tumors in each period was 38, 29, and 30 mm, respectively. The percentage of tumors with positive ER expression was 62.5%, 64.3%, and 69.7%, respectively. In terms of surgical procedures, the use of Halsted's radical mastectomy decreased during each period: from 40.6% of cases to 8.5% and then to 0.4%, while the proportion of breast-conserving therapies increased, from 0% to 12.5%, and finally to 35.9%. The postoperative 10-year survival rates during the three periods were 75.9%, 83.5%, and 84.9%, respectively. The 10-year survival rates of patients with stage II disease during the three periods were 66.2%, 75.7%, and 90.7%, respectively. The prognosis of stage III disease in the three periods also showed a tendency toward improvement, increasing from 37.8% to 64.2%, and finally to 84.5%. CONCLUSION: The survival of patients with stage II and III disease has improved during the past 30 years. Along with the recent advances in drug therapy, the surgical treatment has become less invasive, often because of drug therapy-related modifications.     

Effect of Cystone on urinary composition and stone formation over a one year period

Kidney stones are a common problem for which inadequate prevention exists. We recruited ten recurrent kidney stone formers with documented calcium oxalate stones into a two phased study to assess safety and effectiveness of Cystone^®, an herbal treatment for prevention of kidney stones. The first phase was a randomized double-blinded 12 week cross over study assessing the effect of Cystone^® vs. placebo on urinary supersaturation. The second phase was an open label one year study of Cystone^® to determine if renal stone burden decreased, as assessed by quantitative and subjective assessment of CT. Results revealed no statistically significant effect of Cystone^® on urinary composition short (6 weeks) or long (52 weeks) term. Average renal stone burden increased rather than decreased on Cystone^®. Therefore, this study does not support the efficacy of Cystone^® to treat calcium oxalate stone formers. Future studies will be needed to assess effects on stone passage, or on other stone types.     

Regional trends of minimally invasive radical hysterectomy for cervical cancer and exploration of perioperative outcomes

IntroductionRadical hysterectomy (RH) with bilateral pelvic lymph node dissection is the standard treatment for early stage cervical cancer which can be performed either by an abdominal or a minimally invasive (MIS) approach. In 2018, Ramirez et al. presented their randomized-controlled trial data which demonstrated that patients who were treated with minimally invasive surgical (MIS) radical hysterectomy (RH) had higher rates of locoregional disease recurrence and lower rates of overall survival when compared to patients treated with an abdominal approach. The objective of this study is to examine the trends in management of patients diagnosed with cervical cancer in New York State (NYS) and to analyze their perioperative outcomes.MethodsUsing the Statewide Planning and Research Cooperative System (SPARCS) Database, patients undergoing RH for early stage cervical cancer in NYS between the years of 2007–2015 were identified and categorized based on surgical approach. Demographic information was collected and multivariable regression was conducted to assess the impact of hysterectomy approach on perioperative outcomes.ResultsIn NYS, 5575 patients were treated with RH for early stage cervical cancer with 3257 (58.4%) treated by abdominal RH and 2318 (41.6%) treated with MIS RH. Between the years of 2007 and 2015, patients diagnosed with cervical cancer treated with MIS RH increased from 25.7% to 48.3% respectively. Surgeons performing MIS RH were more likely to be younger (average age 47.1 vs 49.2, p < 0.001) and have less time elapsed from their fellowship graduation (20.37 vs 22.64 years, p < 0.001). Patients who saw high volume doctors (OR 1.95, CI 1.65–2.31) and were seen in high volume facilities (OR 1.40, CI 1.18–1.65) were more likely to undergo MIS RH compared to abdominal RH. Patients who underwent MIS RH were more likely to be discharged home as opposed to acute rehab or nursing facility, when compared to patients treated with abdominal RH (98.5 vs 94.2% p < 0.001). When analyzing perioperativce outcomes, patient undergoing MIS RH had a 85% decrease in length of hospital stay compared to abdominal RH, a 40% reduction in 30-day readmission rates, and a 10% reduction in hospital costs respectively.DiscussionIn our study period, between the years of 2007 and 2015, the number of cervical cancer cases treated with MIS RH increased from 25.7% to 48.3%. MIS techniques led to a reduction in length of hospital stay, patient readmission rates, and hospital costs. Based on recent data from Ramirez et al., preliminary data demonstrated decrease in MIS RH for treatment of cervical cancer after presentation of the LACC trial and our data confirmed these reported trends in NYS. With this change in surgical practice, there will be associated changes in perioperative outcomes. Moreover, for patients diagnosed with cervical cancer with microscopic disease or previous treatment with an excisions procedure, MIS approach should be considered for improvement in perioperative outcomes as long as oncologic outcomes are not compromised.