Long-term outcomes of three-dimensional conformal radiation therapy combined with neoadjuvant hormonal therapy for Japanese patients with T1c-T2N0M0 prostate cancer

Background

The outcomes of three-dimensional conformal radiation therapy (3D-CRT) combined with neoadjuvant hormonal therapy (NAHT) in Japanese patients with T1c-T2N0M0 prostate cancer, with initiation of salvage hormonal therapy (SHT) at a relatively early phase, were analyzed.

Methods

Fifty-nine Japanese patients with T1c-T2N0M0 prostate cancer who received radical 3D-CRT between January 1999 and January 2003 were evaluated. The median age, initial prostate-specific antigen (PSA) level, and duration of NAHT were: 72 years, 9.4 ng/ml, and 6 months, respectively. Seventy Gy was given in 35 fractions confined to the prostate ± seminal vesicles. AHT was not administered after 3D-CRT in any patients.

Results

The median follow-up period was 89 months. The median PSA value at the time of initiation of SHT was 4.7 ng/ml (range 0.1?C21.6 ng/ml). The overall, disease-specific, PSA failure-free (based on the Phoenix definition), and SHT-free survival rates at 8 years were 82.8% (95% confidence interval [CI] 72.4?C93.2), 100%, 62.4% (47.1?C77.8), and 82.6% (71.3?C94.0), respectively. Only one patient developed grade 3 late toxicity.

Conclusions

The PSA control rates in our series of Japanese patients with stage T1c-T2N0M0 prostate cancer treated with the standard dose of 3D-CRT combined with NAHT seemed at least comparable to those reported from Western countries; as well, the patients had excellent outcomes. The present outcomes can be used as basic data for evaluating the impact of dose escalation with intensity-modulated radiation therapy for Japanese patients with prostate cancer in the future.     

Components of the metabolic syndrome and risk of prostate cancer: the HUNT 2 cohort, Norway

Background

The metabolic syndrome has been suggested as a unifying link between a “western” lifestyle and an increased prostate cancer risk.

Methods

We assessed the associations of components of the metabolic syndrome with prostate cancer in a prospective cohort based on 29,364 Norwegian men followed up for prostate cancer incidence and mortality from 1995–1997 to the end of 2005 in the second Nord Trøndelag Health Study (HUNT 2).

Results

During a mean 9.3 years follow-up, 687 incident prostate cancers were diagnosed, and 110 men died from prostate cancer. There was little evidence that baseline BMI, waist circumference, waist–hip ratio, total or HDL-cholesterol, triglycerides, presence of the metabolic syndrome, diabetes, antihypertensive use, or cardiovascular disease were associated with incident or fatal prostate cancer. There was weak evidence that raised blood pressure was associated with an increased risk: for each SD (12 mm) increase in diastolic blood pressure, there was an 8% (95% CI = 1–17%; p = 0.04) increased risk of incident prostate cancer.

Conclusions

We found little evidence to support the hypothesis that the metabolic syndrome or its components explains higher prostate cancer mortality rates in countries with a “western” diet and lifestyle. The positive association of blood pressure with prostate cancer warrants further investigation.     

Prostate cancer screening by prostate-specific antigen (PSA); a relevant approach for the small population of the Cayman Islands

Introduction

The common tool for diagnosing prostate cancer is prostate-specific antigen (PSA), but the high sensitivity and low specificity of PSA testing are the problems in clinical practice. There are no proper guidelines to investigate the suspected prostate cancer in the Cayman Islands. We correlated PSA levels with the incidence of prostate cancers by tissue diagnosis and proposed logical protocol for prostate screening by using PSA test in this small population.

Materials and methods

A total of 165 Afro Caribbean individuals who had prostate biopsy done after the investigations for PSA levels from year 2005 to 2015 were studied retrospectively. The patients were divided into subgroups by baseline PSA levels as follows: <4, 4.1–10, 10.1–20, 20.1–50, 50.1–100, and >100 ng/mL and were correlated to the age and presence of cancer.

Results and discussion

Benign lesions had lower PSA levels compared to cancer which generally had higher values. Only three cases that had less than 4 ng/mg were turned out to be malignant. When PSA value was more than 100 ng/mL, all the cases were malignant. Between PSA values of 4–100 ng/mL, the probability of cancer diagnosis was 56.71% (76 cancers out of 134 in this range). Limitation of PSA testing has the risk of over diagnosis and the resultant negative biopsies owing to poor specificity. Whereas the cutoff limit for cancer diagnosis still remains 4 ng/mL from our study, most of the patients can be assured of benign lesion below this level and thus morbidity associated with the biopsy can be prevented. When the PSA value is greater than 100 ng, biopsy procedure was mandatory as there were 100% cancers above this level.

Summary

On the background of vast literature linking PSA to prostate cancer and its difficulty in implementing in clinical practice, we studied literature of this conflicting and complex topic and tried to bring relevant protocols to the small population of Cayman Islands for the screening of prostate cancer. In this study, a total of 165 Afro Caribbean individuals who had prostate biopsy done after the investigations for PSA levels from year 2005 to 2015 were studied retrospectively. As a result of this research work, it can be concluded that a benign diagnosis can be given with a fair certainty when the PSA was below 4 ng/mL and a level of 100 ng/mL can be very unfavorable for the patients. This study helped to solidify the cancer screening protocols in Cayman Islands.

Conclusion

The PSA level can reassure and educate the patients towards the diagnosis of cancer of prostate in Cayman Islands. Benign diagnosis can be given with a fair certainty when the PSA was below 4 ng/mL and a level of 100 ng/mL can be very unfavorable for the patients. This study helped to solidify the cancer screening protocols in Cayman.

     

Developing new age-specific prostate-specific antigen thresholds for testing for prostate cancer

Purpose

To examine whether age-related reference ranges for “normal” prostate-specific antigen (PSA) change (determined in men without prostate cancer) can be used to identify men at high risk of having prostate cancer.

Methods

Subjects were men aged 50–69 years with PSA?<?10 ng/mL from the UK-based Prostate Testing for cancer and Treatment (ProtecT) study. Men with prostate cancer were categorized as high or low risk of progression (Low risk: Gleason score?≤?6 and stage T1–T2a; High risk: Gleason score 7–10 or stage T2C). Men without prostate cancer were those with no histological confirmation of prostate cancer. Previously developed longitudinal reference ranges for normal age-related PSA change were used to calculate an age-specific PSA threshold. We compared the ability of our age-specific PSA threshold to discriminate between high- and no/low-risk prostate cancer with that of two existing thresholds: (i) threshold of PSA?=?3 ng/ml for all ages; (ii) National Institute of Clinical Excellence (NICE) guidelines dependent on age-group thresholds (age 50–59: PSA?=?3 ng/mL; age 60–70: PSA?=?4 ng/mL; age?≥?70: PSA?=?5 ng/mL).

Results

We included 823 men with high-risk prostate cancer and 80,721 men with no/low-risk prostate cancer. A threshold of PSA?=?3 ng/ml for all ages identified more high-risk prostate cancers, recommending biopsy in 9.8% of men, of which 10.3% (n?=?823) had high-risk prostate cancer. Using the NICE guidelines as the threshold for biopsy, 6.9% men were recommended for biopsy, of which 11.9% (n?=?668) had high-risk prostate cancer. Using the new age-specific threshold for biopsy, 2.3% men were recommended for biopsy, of which 15.2% (n?=?290) had high-risk prostate cancer. The age-specific threshold identified fewer high-risk prostate cancers, but fewer men received unnecessary biopsy.

Conclusion

There is no benefit to using reference ranges for “normal” PSA that change with age nor the age-specific thresholds suggested by the NICE guidelines. While the age-varying thresholds are more discriminatory, too many high-risk cancers are missed.

     

Disparities in time trends of cervical cancer mortality rates in Brazil

Purpose

This study aimed to correct and describe cervical cancer mortality rates and trends by regions and age-groups in Brazil. It may help planning and implementing policies for cervical cancer control.

Methods

Data from 2003 to 2012 were accessed through the centralized national mortality database. Correction of the age-specific mortality rates was done by proportional redistribution of ill-defined causes of death and deaths coded as ‘uterine, part unspecified’. Annual percentage change (APC) was obtained by trend analysis (Joinpoint regression).

Results

In the 10-year period, cancer and ill-defined causes corresponded, respectively, to 18.9 and 10.8 % of all deaths (except injuries). The proportion of ill-defined causes was reduced by more than a half in the period. The age-standardized cervical cancer mortality rate was 7.2 per 100,000 women-years after correction. The total increase in rates after corrections was 50.5 %. A significant decreasing trend in rates was observed at the national level (APC = ?0.17, p < 0.001). North was the only region that did not show a decreasing significant trend (APC + 0.07, p = 0.28). Decreasing trends were restricted to age-groups over 40 years.

Conclusions

A consistent decreasing trend of cervical cancer mortality rates in Brazil from 2003 to 2012 was observed, although this was not consistent in all regions and restricted to older age-groups. Quality of data needs to be improved. Cancer control policies may consider the differences in access to care and the characteristics of regions to improve their efficiency.

     

Preoperative prognostic factors for biochemical recurrence after robot-assisted radical prostatectomy in Japan

Purpose

We investigated oncological outcomes in Japanese patients who underwent robot-assisted radical prostatectomy (RARP).

Materials and methods

This study included 389 patients who underwent RARP at a single institution with a follow-up period of at least 1 year. Preoperative findings were compared with biochemical recurrence (BCR). Predictors of BCR-free survival (BCRFS) were evaluated by univariate and multivariate Cox proportional hazard model analyses, and a risk stratification model based on the relative risks of BCR was established.

Results

Fifty incidences of BCR were noted during a median follow-up period of 28.7 months (range, 12.1–80.0 months). The BCRFS rate for the entire cohort at the median follow-up time was 85.9 %; the 1-, 3-, and 5-year estimates were 91.0, 85.1, and 81.1 %, respectively. From univariate analyses, prostate-specific antigen (PSA), PSA density, biopsy Gleason score, and percent positive core were significantly associated with BCR. Multivariate analysis showed that PSA [hazard ratio (HR), 2.75; p = 0.001], percent positive core (HR, 2.22; p = 0.001), and biopsy Gleason score (HR, 2.61; p = 0.007) were independent predictors of BCR.

Conclusion

This study at a single Japanese center demonstrates that RARP provides a satisfactory BCRFS rate. This report provides a framework with which to estimate oncological outcomes in patients who underwent RARP for localized prostate cancer. Our results support the increased use of RARP for the treatment of localized prostate cancer in Japan.     

Italianity is associated with lower risk of prostate cancer mortality in Switzerland

Purpose

Different prostate cancer mortality rates observed in European countries may depend on cultural background. We aimed at exploring variation in prostate cancer mortality in the language regions of Switzerland as a function of “Italianity”, a proxy for adherence to an Italian lifestyle.

Methods

We used data of the Swiss National Cohort, a census-based record linkage study, consisting of census (1990 and 2000) and mortality (until 2008) data. 1,163,271 Swiss and Italian nationals 40+-year old were included. Multivariate age-standardized prostate cancer mortality rates and hazard ratios (HR) from Cox proportional hazards regression analysis were performed. Italianity was defined by an individual’s nationality, place of birth and principal language, resulting in a score of 0–3 points.

Results

Age-standardized prostate cancer mortality rates (per 100,000 person-years) were lowest in the Italian-speaking region of Switzerland (66.7 vs. 87.3 in the German-speaking region). Both Italian nationality and/or place of birth were significantly associated with lower mortality. There was a graded inverse association between mortality rates and increasing Italianity score. Individuals with the highest level of Italianity had a HR of 0.67 (95 % CI 0.59–0.76) compared to those with an Italianity score of zero. Results were similar when looking at language regions separately.

Conclusions

The strong and consistent association between Italianity and prostate cancer mortality suggests protective properties of an Italian lifestyle. Further research is required in order to determine which factors specific for Italian culture are responsible for the lower prostate cancer mortality.     

The association between race and prostate cancer risk on initial biopsy in an equal access,multiethnic cohort

Purpose

Population-based studies have established a link between race and prostate cancer (PC) risk, but whether race predicts PC after adjusting for clinical characteristics is unclear. We investigated the association between race and risk of low- and high-grade PC in men undergoing initial prostate biopsy in an equal access medical center.

Methods

We conducted a retrospective record review of 887 men (48.6 % black, 51.4 % white) from the Durham Veterans Affairs Medical Center who underwent initial prostate biopsy between 2001 and 2009. Multivariable logistic regression analysis of race and biopsy outcome was conducted adjusting for age, body mass index, number of cores taken, prostate-specific antigen (PSA), and digital rectal examination findings. Multinomial logistic regression was used to test the association between black race and PC grade (Gleason <7 vs. ≥7).

Results

Black men were younger at biopsy (61 vs. 65 years, p < 0.001) and had a higher pre-biopsy PSA (6.6 vs. 5.8 ng/ml, p = 0.001). A total of 499 men had PC on biopsy (245 low grade; 254 high grade). In multivariable analyses, black race was significantly predictive of PC overall [odds ratio 1.50, p = 0.006] and high-grade PC [relative risk ratio (RRR) 1.84, p = 0.001], but was not significantly associated with low-grade PC (RRR 1.29, p = 0.139).

Conclusion

In an equal access healthcare facility, black race was associated with greater risk of PC detection on initial biopsy and of high-grade PC after adjusting for clinical characteristics. Additional investigation of mechanisms linking black race and PC risk and PC aggressiveness is needed.     

Body mass index and weight change in men with prostate cancer: progression and mortality

Purpose

Body mass index (BMI) is a modifiable lifestyle factor that has been associated with an increased risk of fatal prostate cancer and biochemical recurrence. The main purpose of the present study was to investigate the association between the exposure BMI at the time of a prostate cancer diagnosis and weight change after diagnosis, and the outcomes of prostate cancer progression and mortality in a large cohort study.

Methods

Data from 4,376 men diagnosed with clinically localized prostate cancer between 1997 and 2002 were analyzed. BMI and weight change were self-reported in 2007. Hazard ratios (HRs) with 95 % confidence intervals (CIs) were estimated in complete-case analysis (n = 3,214) using Cox proportional hazards models.

Results

Progression was experienced among 639 (14.6 %) of the study participants, and in total, 450 (10.3 %) deaths of any cause and 134 (3.1 %) prostate cancer-specific deaths were recorded during follow-up. Obese men had a 47 % increased rate of overall mortality compared to normal weight men (HR 1.47, 95 % CI 1.03–2.10). No statistically significant associations were found for BMI and prostate cancer progression or prostate cancer-specific mortality. A weight loss >5 % after diagnosis almost doubled the rate of overall mortality compared to maintaining a stable weight (HR 1.94, 95 % CI 1.41–2.66), while a weight gain >5 % was associated with an almost doubled increased rate of prostate cancer-specific mortality (HR 1.93, 95 % CI 1.18–3.16).

Conclusions

Being obese was associated with an increased rate of overall mortality, and gaining weight after a prostate cancer diagnosis was associated with an increased rate of prostate cancer-specific mortality.     

Operative Therapie des lokal begrenzten Prostatakarzinoms

Background

Radical prostatectomy is the most frequently used therapy for localized prostate cancer. Staging measures are based on the preoperative parameters prostate-specific antigene (PSA) level, the Gleason score of biopsy material and the results of the digital rectal examination for diagnostics of the extent of tumor spread. For low risk cancers (PSA <?10 ng/ml, cT1c–cT2a and Gleason sum ≤?6) no further imaging diagnostics should be performed.

Results

Radical prostatectomy can be performed by open surgery (ORP), laparoscopically (LRP) or robot-assisted (RALP). In a prospective randomized trial radical prostatectomy significantly reduced local progression, distant metastases and prostate cancer mortality compared to watchful waiting. Progression-free survival after radical prostatectomy is >?80?% after 7 years and cancer-specific survival rates of >?90?% after 15 years have been reported. Perioperative complications are observed in 9?% of the patients. In recent retrospective studies incontinence rates between 8 and 11?% were reported. Depending on tumor stage a nerve sparing approach is possible and results in postoperative potency rates between 50 and 90?%.

Conclusions

Surgeons experience is of paramount importance for the outcome of radical prostatectomy. Furthermore, comparisons of retrospective data suggest that RALP improves a number of short-term outcomes. Two randomized studies showed concordantly significantly better continence and potency rates after RALP compared to conventional LRP.     

Type 2 diabetes and the risk of mortality among patients with prostate cancer

Purpose

The aim of this study was to determine whether type 2 diabetes is associated with the incidence of prostate cancer mortality and all-cause mortality.

Methods

This study was conducted by linking four databases from the United Kingdom: the National Cancer Data Repository, the Clinical Practice Research Datalink, the Hospital Episodes Statistics database, and the Office for National Statistics database. The cohort consisted of men newly diagnosed with non-metastatic prostate cancer between 1 April 1998 and 31 December 2009, followed until 1 October 2012. Cox proportional hazard models were used to estimate adjusted hazard ratios with 95 % confidence intervals (CIs) of prostate cancer mortality and all-cause mortality comparing patients with to without type 2 diabetes. All models were adjusted for a number of potential confounders, which included excessive alcohol use, smoking, comorbidities, and prostate cancer-related variables.

Results

The cohort consisted of 11,920 patients, which included 1,132 (9.5 %) with preexisting type 2 diabetes. During a mean follow-up of 4.7 (SD 3.0) years, there were 3,605 deaths (incidence rate: 6.4 %/year) including 1,792 from prostate cancer (incidence rate: 3.3 %/year). Type 2 diabetes was associated with a 23 % increased risk of prostate cancer mortality (HR 1.23, 95 % CI 1.04–1.46) and a 25 % increased risk in all-cause mortality (HR 1.25, 95 % CI 1.11–1.40).

Conclusions

The results of this large population-based study indicate that type 2 diabetes is associated with an increased risk of prostate cancer mortality and all-cause mortality, which may signal an association between hyperinsulinemia or other diabetes-associated metabolic derangements and cancer aggressivity.     

Possible anti-tumor activity of initial treatment with zoledronic acid with hormonal therapy for bone-metastatic prostate cancer in multicenter clinical trial

Background

To ascertain the anti-tumor effect of zoledronic acid (ZOL) treatment on clinical outcomes in patients with bone metastatic prostate cancer, we examined the effect of ZOL started simultaneously with hormonal therapy as initial treatment in these patients.

Methods

Forty-seven patients with bone-metastatic prostate cancer who received a luteinizing hormone releasing-hormone (LHRH) analogue and an anti-androgen [maximal androgen blockade (MAB)] were assigned to receive ZOL (4 mg intravenous administration every month for 2 years). The time to progression (TTP) of the prostate-specific antigen (PSA), the overall survival (OS), and the rate of PSA decrease in patients with MAB and ZOL treatment (ZOL group) were compared with these parameters in patients who received only MAB at one institute as a control group (non-ZOL group).

Results

Although the nadir PSA level and the rate of PSA normalization showed no significant differences between the ZOL and non-ZOL groups, the time to nadir PSA in the ZOL group was significantly shorter than that in the non-ZOL group (P < 0.05, Mann–Whitney U-test). There was a significant difference in TTP (P = 0.017, log-rank test) between the ZOL and non-ZOL groups, and statistically significant differences in TTP and OS between the ZOL and non-ZOL groups (P = 0.044 and 0.035, log-rank test) were recognized particularly in patients with advanced disease (extension of disease, grade 3 and 4).

Conclusions

Simultaneous administration of ZOL and MAB as initial treatment delayed TTP in bone-metastatic prostate cancer patients. Initial treatment with ZOL has the possibility of anti-tumor activity to delay disease progression.     

A prospective study of socioeconomic status, prostate cancer screening and incidence among men at high risk for prostate cancer

Purpose

Higher socioeconomic status (SES) men are at higher risk of prostate cancer (PCa) diagnosis, an association commonly interpreted as a function of higher rates of prostate screening among higher SES men. However, the extent to which screening explains this association has not been well quantified.

Methods

Within a Detroit area cohort of 6,692 men followed up after a benign prostate procedure, a case–control study was conducted of 494 PCa cases and controls matched on age, race, duration of follow-up, and date of initial benign finding; 2000 Census data were used in a principal component analysis to derive a single factor, labeled the neighborhood SES index (NSESI), representing zip code-level SES.

Results

Among cases, higher SES was associated with a younger age at initial biopsy: ?1.48 years (95 % CI, ?2.32, ?0.64) per unit NSESI. After adjustment for confounders and duration of follow-up, higher SES was associated with more PSA tests and DRE during follow-up; 9 % (95 % CI, 2, 16) and 8 % (95 % CI, 1, 15) more respectively, per unit NSESI. Higher SES was associated with a higher risk of PCa diagnosis during follow-up, multivariable adjusted OR = 1.26 per unit increase in NSESI (95 % CI, 1.04, 1.49). Further adjustment for screening frequency somewhat reduced the association between SES and PCa risk (OR = 1.19 per unit NSESI, 95 % CI, 0.98, 1.44).

Conclusions

Differences in screening frequency only partially explained the association between higher zip code SES and PCa risk; other health care-related factors should also be considered as explanatory factors.     

A phase II study of fenretinide in patients with hormone refractory prostate cancer: a trial of the Cancer Therapeutics Research Group

Purpose

Fenretinide is a synthetic retinoid with activity in prostate cancer and other cell lines. The aim of this study was to assess the efficacy and tolerability of fenretinide in chemotherapy-naïve men with hormone refractory prostate cancer.

Methods

Eligibility criteria included hormone refractory prostate cancer with a rising PSA at least 6 weeks after peripheral anti-androgen withdrawal, ECOG performance status (PS) 0–1, and no prior chemotherapy. Fenretinide was administered orally at 900 mg m^?2 twice daily for 7 of every 21 days. PSA was measured before each cycle. The primary endpoint was a ≥50% reduction in PSA maintained for at least 3 weeks; secondary endpoints included duration of PSA response, time to treatment failure (TTF: treatment stopped for progression or toxicity) and adverse events (AE).

Results

Twenty seven pts were recruited from 7 centres over 27 months. Median age was 74 (range 49–86), median baseline PSA was 129 (range 19–1,000), and 70% had a PS of 0. The median number of cycles received was 2 (range 0–11) and 20 pts completed at least 1 cycle. One pt (4%) achieved a 50% reduction in PSA lasting 39 days and 15 pts (56%) had not progressed within 6 weeks of starting fenretinide. The median TTF was 54 days (IQR 19–73): 22 (81%) failed with tumour progression, 3 (11%) failed with toxicity and 2 (7%) never commenced the drug. Grade 3 rash occurred in 1 patient, all other AE were grade 1 or 2. The most common AE were nausea (40%), hot flushes (36%), constipation (32%) and nyctalopia (32%).

Conclusion

High-dose fenretinide had limited anti-tumour activity in patients with advanced hormone refractory prostate cancer: further evaluation in this setting is not warranted.     

Prostate cancer clinical presentation,incidence, mortality and survival in Guadeloupe over the period 2008–2013 from a population-based cancer registry

Purpose

The Caribbean population of Guadeloupe has one of the highest incidence rates of prostate cancer worldwide. In 2008, a population-based cancer registry was set up for the monitoring of cancer incidence in the aftermath of the environmental pollution with chlordecone, a persistent organochlorine insecticide formerly used in banana plantations. We describe the clinical presentation, incidence, mortality and survival of prostate cancer for the period 2008–2013.

Methods

The Guadeloupe cancer registry has been routinely collecting all incident cases of cancer since 2008. We compared age-specific incidence rates between different populations, and calculated incidence and mortality rates standardized to the world population. Kaplan–Meier observed survival and estimated age-standardized net survival were calculated by category for age, PSA level, and Gleason score using the Pohar-Perme method.

Results

Overall, 3,295 cases of prostate cancer were recorded. World-standardized incidence and mortality were respectively 184.1 [177.8–190.4] and 23.9 [21.9–25.7] per 100,000 person-years. At diagnosis, the mean age of patients was 68?±?9.6 years old and 22% were aged over 75. Median PSA level was 8.9 [IQR: 6.0–16.0] and 13.6% of the patients had a Gleason?≥?8. Five-year observed and net survivals were, respectively, 79.6% [77.9–81.2] and 90.7% [88.6–92.8].

Conclusion

The incidence of prostate cancer in Guadeloupe is among the highest in the world, along with those of the neighboring Caribbean countries and US African-Americans. We observed no decrease in incidence rates, and a decreasing but non-significant trend in mortality rates, which nonetheless remain higher than in high-income countries. Many Genome-Wide Association Studies are conducted to identify genetic markers involved in prostate cancer risk. In the Caribbean, complementary studies on both lifestyle and behavioral factors should highlight potential common risks among populations who share both genetic and environmental characteristics.

     

Surveillance biopsy and active treatment during active surveillance for low-risk prostate cancer

Background

The goals of the study were to examine surveillance biopsy and active treatment in patients under active surveillance (AS) for low-risk prostate cancer and to determine the active treatment-free survival rate.

Methods

The subjects were 87 patients with low-risk prostate cancer who were under AS between 2000 and 2010. The eligibility criteria for AS were T1c, Gleason score ≤6, prostate-specific antigen level ≤10 ng/ml, one or two positive biopsies, maximum cancer involvement ≤50 %, and age ≤80 years old.

Results

Of the 87 patients, 48 underwent the first surveillance biopsy (55.2 %). In this biopsy, no cancer was found in 33.3 % of cases, 27.1 % remained eligible for AS, and 39.6 % did not meet the AS criteria (up-grade 22.9 %, up-volume 16.7 %). A second surveillance-biopsy was performed at 1.9 years after the first biopsy. No cancer was found in 20.0 % of cases, 40.0 % remained eligible for AS, and 40.0 % did not meet the AS criteria (up-grade 26.7 %, up-volume 13.3 %). A total of 50 patients received treatment by 1.7 years after starting AS, mainly due to an up-grade or up-volume. However, some patients underwent radiotherapy despite biopsy results indicating no cancer or eligibility for AS. The active treatment-free survival rate was 64.1 % after 2 years.

Conclusions

Surveillance biopsy is important for identifying patients who require active treatment. The results in this study allowed determination of the active treatment-free survival rate and are informative for making treatment decisions.     

Serum folate and prostate-specific antigen in the United States

Purpose

Increased evidence suggests that folate may play a significant role in cancer development. This study investigates the association between levels of serum folate and prostate-specific antigen (PSA), a biomarker for prostate cancer detection.

Methods

Using data from the 2007 to 2010 National Health and Nutrition Examination Survey, a total of 3,293 men aged 40 years and older with serum PSA and folate measures were studied. Total PSA level (tPSA) and percent free/total PSA ratio (%fPSA) were major outcomes. The alternative cutpoints were used to categorize these measures as higher risks of prostate cancer (tPSA: ≥10, ≥4, and ≥2.5 ng/ml; %fPSA: ≤15 and ≤5 %). Serum folate level was analyzed as continuous and as quintiles. Association between serum folate and PSA levels were evaluated by multivariate linear and logistic regressions.

Results

Higher serum folate levels were associated with decreased log10-transformed tPSA (β = ?001, p = 0.061) and increased %fPSA (β = 0.064, p = 0.012). Adjusting for age, race/ethnicity, socioeconomic status, use of non-steroidal anti-inflammatory drugs, body mass index, and smoking status, higher serum folate (fifth quintile) was associated with lower odds of having higher tPSA (≥10 ng/ml) and lower %fPSA (≤25 %): (tPSA: odds ratio, OR associated with fifth to first quintile of folate level = 0.42; 95 % confidence interval, CI = 0.21, 0.83; p for trend = 0.022 and %fPSA: OR = 0.71; 95 % CI = 0.52, 0.95; p for trend = 0.044).

Conclusions

Results of this study suggest that higher folate status may be protective against elevated PSA levels among men without diagnosed prostate cancer. Additional epidemiologic studies are necessary to confirm our findings and to investigate potential mechanisms.     

A phase 2 study of intravenous panobinostat in patients with castration-resistant prostate cancer

Purpose

Panobinostat, a pan-deacetylase inhibitor, increases acetylation of proteins associated with growth and survival of malignant cells. This phase 2 study evaluated the efficacy of intravenous (IV) panobinostat in patients with castration-resistant prostate cancer (CRPC) who had previously received chemotherapy. The primary end point was 24-week progression-free survival. Secondary end points included safety, tolerability, and the proportion of patients with a prostate-specific antigen (PSA) decline.

Methods

IV panobinostat (20 mg/m²) was administered to patients on days 1 and 8 of a 21-day cycle. Tumor response was assessed by imaging every 12 weeks (4 cycles) according to modified response evaluation criteria in solid tumors (Scher et al. in Clin Cancer Res 11:5223–5232, 23), and PSA response was defined as a 50 % decrease from baseline maintained for ≥4 weeks. Safety monitoring was routinely performed and included electrocardiogram monitoring.

Results

Of 35 enrolled patients, four (11.4 %) were alive without progression of disease at 24 weeks. PSA was evaluated in 34 (97.1 %) patients: five (14.3 %) patients demonstrated a decrease in PSA but none ≥50 %; one patient (2.9 %) had carcinoembryonic antigen as a marker of his prostate cancer, which declined by 43 %. Toxicities regardless of relationship to panobinostat included fatigue (62.9 %), thrombocytopenia (45.7 %), nausea (51.4 %), and decreased appetite (37.1 %).

Conclusions

Despite promising preclinical data and scientific rationale, treatment with IV panobinostat did not show a sufficient level of clinical activity to pursue further investigation as a single agent in CRPC.     

Investigating the prostate specific antigen,body mass index and age relationship: is an age–BMI-adjusted PSA model clinically useful?

Purpose

Previous studies indicate a possible inverse relationship between prostate-specific antigen (PSA) and body mass index (BMI), and a positive relationship between PSA and age. We investigated the associations between age, BMI, PSA, and screen-detected prostate cancer to determine whether an age–BMI-adjusted PSA model would be clinically useful for detecting prostate cancer.

Methods

Cross-sectional analysis nested within the UK ProtecT trial of treatments for localized cancer. Of 18,238 men aged 50–69 years, 9,457 men without screen-detected prostate cancer (controls) and 1,836 men with prostate cancer (cases) met inclusion criteria: no history of prostate cancer or diabetes; PSA < 10 ng/ml; BMI between 15 and 50 kg/m². Multivariable linear regression models were used to investigate the relationship between log-PSA, age, and BMI in all men, controlling for prostate cancer status.

Results

In the 11,293 included men, the median PSA was 1.2 ng/ml (IQR: 0.7–2.6); mean age 61.7 years (SD 4.9); and mean BMI 26.8 kg/m² (SD 3.7). There were a 5.1% decrease in PSA per 5 kg/m² increase in BMI (95% CI 3.4–6.8) and a 13.6% increase in PSA per 5-year increase in age (95% CI 12.0–15.1). Interaction tests showed no evidence for different associations between age, BMI, and PSA in men above and below 3.0 ng/ml (all p for interaction >0.2). The age–BMI-adjusted PSA model performed as well as an age-adjusted model based on National Institute for Health and Care Excellence (NICE) guidelines at detecting prostate cancer.

Conclusions

Age and BMI were associated with small changes in PSA. An age–BMI-adjusted PSA model is no more clinically useful for detecting prostate cancer than current NICE guidelines. Future studies looking at the effect of different variables on PSA, independent of their effect on prostate cancer, may improve the discrimination of PSA for prostate cancer.

     

Evaluating long-term patient-centered outcomes following prostate cancer treatment: findings from the Michigan Prostate Cancer Survivor study

Context

Advances in screening and treatment of prostate cancer have dramatically increased the number of survivors in the US population. Yet the effect of screening is controversial, and in some instances may not be beneficial. Previous studies have typically only reported outcomes of treatment and symptoms within a short time frame following treatment. The persistence of such symptoms over time necessitates an improvement of survivor care so that the medical and support needs of these patients are met.

Objective

This study aims to perform a patient-centered survey of prostate cancer survivors in the Michigan Cancer Registry to identify treatment side effect rates, evaluate survivors' access to preventive care services post-prostate cancer treatment, and assess the informational needs of these survivors regarding their prostate cancer.

Design, setting, and patients

Linking case files of the Michigan Cancer Registry with records from the National Death Index, we identified prostate cancer patients diagnosed between 1985 and 2004 and alive on 31 December 2005. Participants were selected using a stratified cross-sectional sampling strategy to ensure adequate inclusion of survivors based upon race and ethnicity, urban versus rural location, and number of years since diagnosis of prostate cancer. A total of 2,499 surveys were completed and returned.

Main outcome measures

(1) Physical symptoms—assessing bowel, sexual, urinary, and vitality symptoms by treatment modality. (2) Access to care—identifying whether diagnostic tests for prostate cancer (prostate-specific antigen (PSA) and digital rectal examination) were performed. Determining whether the survivors had knowledge of the “watchful waiting” paradigm for prostate cancer surveillance. (3) Informational needs—assessing whether the informational needs of patients were addressed by providers. Evaluating the significant predictors associated with seeking information about prostate cancer from any other source. Identifying what factors influenced a person to actively seek out information and what factors guide which primary information source a survivor would use.

Results

Median duration between prostate cancer diagnosis and survey response was 9 years. Of the study population, 80 % was diagnosed at an early stage. Survivors had reported significant problems in the 4 weeks prior to survey. Of the survivors, 88.1 % reported having a PSA test since diagnosis of prostate cancer, with 93 % of them having it done at least once per year. Of the survivors, 82.6 % reported that a healthcare provider gave them information on prostate cancer. Of this 82.6 %, 86.4 % had this information provided by a urologist, 45.4 % by a primary care physician, and 29.2 % by an oncologist. The primary source of information for these survivors was “healthcare provider” (59.2 %).

Conclusion

Persistent symptoms subsequent to prostate cancer treatment suggest a gap in symptom management. Future research should support long-term studies of active surveillance versus active treatment outcomes to understand the feasibility of minimizing the burden of long-term physical symptoms arising from prostate cancer treatment. Clinicians must assess post-treatment distress long after treatment has ended to identify when supportive care is needed. More informational resources should be allocated to prostate cancer survivors to ensure that they are well-educated about their prognosis.

Implications for Cancer Survivors

This study is needed to ensure that the post-treatment symptoms of prostate cancer survivors are properly addressed and managed by healthcare providers over the long term.