Spacers entre prostate et rectum : optimisation des techniques d’irradiation du cancer de la prostate

In the curative radiotherapy of localized prostate cancer, improvements in biochemical control observed with dose escalation have been counterbalanced by an increase in radiation-induced toxicity. The injection of biodegradable spacers between prostate and rectum represents a new frontier in the optimization of radiotherapy treatments for patients with localized disease. Transperineal injection of different types of spacers under transrectal ultrasound guidance allows creating a 7-to-20 mm additional space between the prostate and the anterior rectal wall lasting 3 to 12 months. Dosimetrically, a relative reduction in the rectal volume receiving at least 70 Gy (V₇₀) in the order of 43% to 84% is observed with all types of spacers, regardless of the radiotherapy technique used. Preliminary clinical results show for all spacers a good tolerance and a possible reduction in the acute side effects rate. The aim of the present systematic review of the literature is to report on indications as well as dosimetric and clinical advantages of the different types of prostate-rectum spacers commercially available (hydrogel, hyaluronic acid, collagen, biodegradable balloon).     

Is “pelvic radiation disease” always the cause of bowel symptoms following prostate cancer intensity-modulated radiotherapy?

Background

Pelvic radiation disease (PRD) also widely known as “radiation proctopathy” is a well recognised late side-effect following conventional prostate radiotherapy. However, endoscopic evaluation and/or specialist referral for new or persistent post-prostate radiotherapy bowel symptoms is not routine and serious diagnoses may potentially be missed. Here we report a policy of endoscopic evaluation of bowel symptoms persisting >90 days post radiotherapy for prostate cancer.

Methods and materials

A consecutive series of 102 patients who had radical prostate intensity-modulated radiotherapy (IMRT)/image-guided radiotherapy (IGRT) and who had new or ongoing bowel symptoms or positive faecal occult blood tests (FOBT) on follow up visits more than three months after treatment, were referred for endoscopic examination. All but one (99%) had full colonoscopic investigation.

Results

Endoscopic findings included gastric/colonic/rectal polyps (56%), diverticular disease (49%), haemorrhoids (38%), radiation proctopathy (29%), gastritis/oesophagitis (8%) and rarer diagnoses, including bowel cancer which was found in 3%. Only four patients (4%) had radiation proctopathy without associated pathology and 65 patients (63%) had more than one diagnosis. If flexible sigmoidoscopy alone were used, 36.6% of patients and 46.6% patients with polyp(s) would have had their diagnoses missed.

Conclusions

Our study has shown that bowel symptoms following prostate IMRT/IGRT are due to numerous diagnoses other than PRD, including malignancy. Routine referral pathways should be developed for endoscopic evaluation/specialist review for patients with new or persistent bowel symptoms (or positive FOBT) following prostate radiotherapy. This recommendation should be considered for incorporation into national guidelines.     

IGRT of prostate cancer; is the margin reduction gained from daily IG time-dependent?

The aim of this study was to assess the set-up uncertainties and the possible CTV-PTV margin reduction when adopting daily IGRT. Further, to identify any intrafraction time trends in the prostate movements to ensure the margin reduction gained from IGRT. Fifteen prostate cancer patients treated with IMRT using daily IG of three implanted fiducial markers were included. The interfraction uncertainties were assessed by statistically evaluating the daily prostate marker displacement. The intrafraction uncertainties were represented by the difference in prostate marker displacement before and after beam delivery. To evaluate any intrafraction time trends, the data points were divided into two groups with respect to time duration and statistically analysed. This study confirmed that daily IG considerably reduces the set-up uncertainties. Our results implied that if IGRT is performed on a daily basis, both systematic and random set-up errors will be reduced to a minimum, leading to a required set-up margin of only 1.5 mm. Results from measurements of intrafraction motions in time durations ranging from 2 to 27 min, indicated that a margin enlargement of 1 mm was required to account for the intrafraction uncertainties. The results did not suggest any significant time trends in the intrafraction uncertainties.     

Is screening for prostate cancer with prostate specific antigen an appropriate public health measure?

Screening and treatment for prostate cancer is controversial. In the absence of randomized trials, several prominent medical organizations in the United States and Europe have formulated policies that range from enthusiastic support to significant skepticism concerning the efficacy of screening and subsequent treatment for prostate cancer. Sharp rises in the incidence of prostate cancer have occurred whenever PSA testing has been introduced on a wide scale. Unfortunately, it is unclear whether declines in prostate cancer mortality can be attributed to PSA testing. Other explanations include the early use of anti-androgen therapy or changes in environmental factors such as diet. Repeated testing for serum PSA has produced significant shifts in the types of cases being identified and has raised the possibility of significant over-diagnosis of this disease. The European screening trial and the PLCO trial in the US will hopefully provide some insights into the value of population-based testing.     

Strontium‐89 treatment for prostate cancer bone metastases: Does a prostate‐specific antigen response predict for improved survival?

A review of 50 patients treated with strontium‐89 for prostate cancer bone metastases from January 1993–1997 at the Wellington Cancer Centre was undertaken to determine if there was any correlation between changes in prostate‐specific antigen (PSA) following treatment and subsequent survival. Thirty cases were evaluable for PSA response. Of these, 14 had a fall in PSA following strontium‐89 treatment, and their mean survival was 641 days. The remaining 16 patients did not demonstrate a post‐treatment fall in PSA and their mean survival was 275 days. A difference between these two groups in the time to development of new bone symptoms following treatment was also observed. No significant correlation between pretreatment PSA and PSA response was observed. In conclusion, a PSA response following strontium‐89 treatment appears to predict for improved survival in patients with bone metastases from carcinoma of the prostate. Further prospective studies are indicated.     

Does androgen‐deprivation therapy accelerate the development of frailty in older men with prostate cancer?

The majority of men with prostate cancer are aged > or =65 years. Men, as they age, are more likely to suffer from impaired physical function. The standard treatment for recurrent prostate cancer is androgen-deprivation therapy (ADT). Well-established toxicities from ADT include lean weight loss or sarcopenia, muscle weakness, fatigue, and reduced activity levels. Frailty is a term from geriatrics that describes older individuals with limited physiologic reserve who are at significant risk for adverse outcomes, including falls, disability, hospitalization, and death. An increasingly accepted definition of frailty is a syndrome in which > or =3 of the following are present: unintentional (lean) weight loss > or =10 pounds in the past year, weakness (measured by grip strength), slow walking speed, self-reported exhaustion, and low physical activity. This clinical syndrome overlaps closely with the known toxicities of ADT. In addition, alterations in the inflammatory system, neuroendocrine system, and energy production are associated with this syndrome, as evidenced by biomarkers such as C-reactive protein, interleukin-6, and tumor necrosis factor-alpha. For this article, the authors reviewed the evidence for the effect of ADT on each of the 5 frailty components plus the identified biomarkers, and the evidence indicates that ADT may accelerate the development of frailty in vulnerable older men with prostate cancer. Given the association of frailty with important clinical outcomes such as hospitalization and death, this potential consequence of ADT should be considered carefully when initiating therapy in older patients with recurrent prostate cancer.     

Do the risk factors of age,family history of prostate cancer or a higher prostate specific antigen level raise anxiety at prostate biopsy?

To date, little is known of the impact knowledge of personal risk factors has on anxiety in men undergoing biopsy tests for prostate cancer. This analysis explores anxiety scores of men at higher risk due to age, family history of prostate cancer and a higher prostate specific antigen (PSA) level when proceeding from PSA test to prostate biopsy. A prospective cohort of 4198 men aged 50–69 years with a PSA result of >3 ng/ml was studied, recruited for the Prostate testing for cancer and Treatment study (ProtecT). Anxiety scores at the time of biopsy were lower in older men (p < 0.001). No age group showed an increase in anxiety as the men proceeded from PSA testing to biopsy, although older men did not show the same level of decrease in anxiety as younger men (p = 0.035). There was no difference in anxiety scores at biopsy between men with or without a family history of prostate cancer (p = 0.68), or between those with a raised PSA of 10–<20 ng/ml compared to a PSA result of 3–<10 ng/ml (p = 0.46). Change in scores since the initial PSA test appeared unaffected by family history (p = 0.995) or by PSA result (p = 0.76). Within the context of a research study, the increased risk of prostate cancer through older age, having a family history of prostate cancer, or having a significantly elevated PSA level appears to have no detrimental effect on men’s anxiety level when proceeding to biopsy.     

Downregulation of <Emphasis Type="Italic">TRPM7</Emphasis> suppressed migration and invasion by regulating epithelial–mesenchymal transition in prostate cancer cells

Metastasis is a leading cause of death in patients with prostate cancer (PCa). Transient receptor potential channel 7 (TRPM7) functions as a Mg²⁺/Ca²⁺-permeable channel as well as a protein kinase that regulate various cellular processes including cell adhesion, migration and survival. However, the function of TRPM7 in metastasis of PCa remains largely unknown. Microarray analysis suggested that calcium signaling pathway was significantly altered in metastatic PCa tissues, compared with benign prostatic hyperplasia tissues. Bioinformatics analysis using microarray data and database for annotation, visualization and integrated discovery database revealed altered genes involved in calcium signaling pathway were significantly upregulated in TRPM7 deficiency PCa cells, which was also confirmed by experimental verification. Therefore, we aim to investigate the role of TRPM7 in human PCa cell migration and invasion as well as the underlying mechanisms. We observed that TRPM7 was upregulated in PCa cells and tissues compared with prostate hyperplasia cells and tissues. Further investigations suggested that TRPM7 deficiency suppressed migration and invasion of distinct PCa cell lines while overexpression of TRPM7 increased migration of PCa cells. In addition, knockdown of TRPM7 in PCa cells reversed the epithelial–mesenchymal transition (EMT) status, accompanied by downregulation of MMPs and upregulation of E-cadherin. Taken together, our study indicated that downregulation of TRPM7 could inhibit migration and invasion via reversing EMT status in PCa cells.     

Who makes the decision regarding the treatment of clinically localized prostate cancer–the patient or physician?

BACKGROUND:

The current study examined how patients' sociodemographic, cancer‐related, and subjective affective factors impacted their role in treatment decision‐making.

METHODS:

The patient sample (N = 788) was taken from a prospective follow‐up study of a population‐based cohort. Participants included 343 African American and 445 Caucasian‐American patients with clinically localized prostate cancer. Multinomial logistic regression was used to investigate relations between the explanatory variables and the nominal 3‐level decision‐making variable: patient‐only, patient‐physician shared, and physician‐only.

RESULTS:

Approximately 41% of patients reported patient‐only decision‐making, 45% reported shared decision‐making, and 13% reported physician‐only decision‐making. The odds of patient‐only over physician‐only decision‐making were greater for younger men (vs those aged ≥ 65 years) (odds ratio [OR], 1.68; 95% confidence interval [95% CI], 1.03‐2.74), and were less for men with high (vs low) cancer aggressiveness (OR,0.29; 95% CI, 0.15‐0.55). The odds of shared over physician‐only decision‐making were less for men with high (vs low) cancer aggressiveness (OR, 0.40; 95% CI, 0.22‐0.73). Greater odds of patient‐only and shared decision‐making also were found to be associated with greater concerns about the physical impact of treatment and having enough time for decision‐making and lower scores of receiving advice from others.

CONCLUSIONS:

The findings of the current study indicate that, to facilitate a more patient‐oriented decision‐making process regarding treatment in those with clinically localized prostate cancer, clinicians need to tailor their interventions according to patient age and cancer aggressiveness, help reduce patient concerns and misconceptions regarding the physical impact of treatments, allow sufficient time for patients to consider treatment options, and assist patients in balancing advice and information received from different sources. Cancer 2013. © 2012 American Cancer Society.     

Is single fraction 15 Gy the preferred high dose-rate brachytherapy boost dose for prostate cancer?

Background and purpose

High dose-rate (HDR) brachytherapy is most commonly administered as a boost in two or more fractions combined with external beam radiotherapy (EBRT). Our purpose is to compare outcomes with a single fraction HDR boost to that with a standard fractionated boost in intermediate risk prostate cancer.

Materials and methods

Results of two sequential phase II clinical trials are compared. The Single Fraction protocol consists of 15 Gy HDR in one fraction followed by 37.5 Gy EBRT in 15 fractions over 3 weeks; the Standard Fractionation protocol consisted of two HDR fractions each of 10 Gy, 1 week apart, followed by 45 Gy EBRT in 25 fractions. Patients had intermediate risk disease, and were well balanced for prognostic factors. Patients were followed prospectively for efficacy, toxicity and health-related quality of life (Expanded Prostate Index Composite). Efficacy was assessed biochemically using the Phoenix definition, and by biopsy at 2 years.

Results

The Single Fraction protocol accrued 123 patients and the Standard Fractionation protocol, 60. With a median follow-up of 45 and 72 months, respectively, the biochemical disease-free survival was 95.1% and 97.9% in the Single and Standard Fractionation trials (p = 0.3528). Two-year prostate biopsy was positive in only 4% and 8%, respectively. There was no difference in late urinary or rectal toxicity rates, or in health-related quality of life between the two protocols.

Conclusions

The Single Fraction HDR protocol results in high disease control rate and low toxicity similar to our previous protocol using two HDR insertions, with significant savings in resources. While mature results with longer follow-up are awaited, a single 15 Gy may be considered as a standard fractionation regimen in combination with EBRT for men with intermediate risk disease.