Combined Ultrasmall Superparamagnetic Particles of Iron Oxide–Enhanced and Diffusion-Weighted Magnetic Resonance Imaging Reliably Detect Pelvic Lymph Node Metastases in Normal-Sized Nodes of Bladder and Prostate Cancer Patients

Background

Lymph node staging of bladder or prostate cancer using conventional imaging is limited. Newer approaches such as ultrasmall superparamagnetic particles of iron oxide (USPIO) and diffusion-weighted magnetic resonance imaging (DW-MRI) have inconsistent diagnostic accuracy and are difficult to interpret.

Objective

To assess whether combined USPIO and DW-MRI (USPIO–DW-MRI) improves staging of normal-sized lymph nodes in bladder and/or prostate cancer patients.

Design, setting, and participants

Twenty-one consecutive patients with bladder and/or prostate cancer were enrolled between May and October 2008. One patient was excluded secondary to bone metastases detected on DW-MRI with subsequent abstention from surgery.

Intervention

Patients preoperatively underwent 3-T MRI before and after administration of lymphotropic USPIO using conventional MRI sequences combined with DW-MRI. Surgery consisted of extended pelvic lymphadenectomy and resection of primary tumors.

Measurements

Diagnostic accuracies of the new combined USPIO–DW-MRI approach compared with the “classic” reading method evaluating USPIO images without and with DW-MRI versus histopathology were evaluated. Duration of the two reading methods was noted for each patient.

Results and limitations

Diagnostic accuracy (90% per patient or per pelvic side) was comparable for the classic and the USPIO–DW-MRI reading method, while time of analysis with 80 min (range 45–180 min) for the classic and 13 min (range 5–90 min) for the USPIO–DW-MRI method was significantly shorter (p < 0.0001). Interobserver agreement (three blinded readers) was high with a kappa value of 0.75 and 0.84, respectively. Histopathological analysis showed metastases in 26 of 802 analyzed lymph nodes (3.2%). Of these, 24 nodes (92%) were correctly diagnosed as positive on USPIO–DW-MRI. In two patients, one micrometastasis each (1.0 × 0.2 mm; 0.7 × 0.4 mm) was missed in all imaging studies.

Conclusions

USPIO–DW-MRI is a fast and accurate method for detecting pelvic lymph node metastases, even in normal-sized nodes of bladder or prostate cancer patients.     

In vivo assessment of prostate cancer aggressiveness using magnetic resonance spectroscopic imaging at 3 T with an endorectal coil

Background

One of the most important clinical challenges in prostate cancer (PCa) management is an in vivo assessment of cancer aggressiveness.

Objective

To validate the performance of magnetic resonance (MR) spectroscopic imaging (MRSI) of the prostate at 3 T for the purpose of assessing tumour aggressiveness based on the ratio of choline plus creatine to citrate (Cho+Cr/Cit) and of choline to creatine (Cho/Cr), using the Gleason score of the radical prostatectomy (RP) specimen as the gold standard.

Design, setting, and participants

A total of 43 biopsy-proven PCa patients with 53 clinically relevant tumour foci were retrospectively included in this study.

Measurements

Patients underwent MR imaging and MRSI examination followed by RP. From MRSI, all spectroscopy voxels containing tumour were selected by a radiologist guided by the prostatectomy histopathology map only. For each tumour, two spectroscopists determined the maximum Cho+Cr/Cit, Cho/Cr, and malignancy rating using a standardised threshold approach, incorporating both metabolic ratios. The maximum Cho+Cr/Cit, Cho/Cr, and malignancy ratings showed a relation to tumour aggressiveness and so were used to differentiate among tumour aggressiveness classes.

Results and limitations

The maximum Cho+Cr/Cit ratio, maximum Cho/Cr ratio, and malignancy rating of a standardised threshold approach separated low-grade from higher-grade tumours, with areas under the receiver operating characteristic (ROC) curves of 0.70, 0.74, and 0.78, respectively.

Conclusions

MRSI offers possibilities for an in vivo, noninvasive assessment of PCa aggressiveness. The combination of the different metabolite ratios was used with promising results for discrimination among different aggressiveness classes.     

Prospective evaluation of 11C-choline positron emission tomography/computed tomography and diffusion-weighted magnetic resonance imaging for the nodal staging of prostate cancer with a high risk of lymph node metastases

Background

Contrast-enhanced computed tomography (CT) and magnetic resonance (MR) imaging for lymph node (LN) staging of prostate cancer (PCa) are largely inadequate.

Objective

Our aim was to assess prospectively the sensitivity, specificity, and positive and negative predictive values for the LN staging by ¹¹C-choline positron emission tomography (PET)-CT and MR diffusion-weighted imaging (DWI) of the pelvis before retropubic radical prostatectomy (RRP) with extended pelvic LN dissection (PLND).

Design, setting, and participants

From February 2008 to August 2009, 36 patients with histologically proven PCa and no pelvic LN involvement on contrast-enhanced CT with a risk ≥10% but ≤35% at LN metastasis according to the Partin tables were enrolled in this study.

Intervention

Patients preoperatively underwent ¹¹C-choline PET-CT and DWI. Subsequently all patients underwent a wide RRP and an extended PLND.

Measurements

Sensitivity, specificity, and positive and negative predictive values (PPV and NPV) for LN status of ¹¹C-choline PET-CT and DWI were calculated with the final histopathology of the LNs as comparator.

Results and limitations

Seventeen patients (47%) had a pN1 stage, and 38 positive LNs were identified. On a LN region-based analysis, sensitivity, specificity, PPV, NPV, and the number of correctly recognised cases at ¹¹C-choline PET-CT were 9.4%, 99.7%, 75.0%, 91.0%, and 7.9%, respectively, and at DWI these numbers were 18.8%, 97.6%, 46.2%, 91.7%, and 15.8%, respectively. Twelve LN regions containing macrometastases, of which 2 had capsular penetration, were not detected by ¹¹C-choline PET-CT; 11 LNs, of which 2 had capsular penetration, were not detected by DWI. This is a small study with 36 patients, but we intend to recruit more patients.

Conclusions

From this prospective histopathology-based evaluation of ¹¹C-choline PET-CT and DWI for LN staging in high-risk PCa patients, it is concluded that these techniques cannot be recommended at present to detect occult LN metastases before initial treatment.     

Bacillus Calmette-Guérin without maintenance therapy for high-risk non-muscle-invasive bladder cancer

Background

Bacillus Calmette-Guérin (BCG) is the standard intravesical treatment of high-risk noninvasive (Ta, T1, Tis) bladder cancer. Maintenance BCG is recommended for maximum efficacy.

Objective

We compared our results in a large cohort of high-risk bladder cancer patients who received BCG without maintenance with published results from randomized maintenance BCG trials.

Design, setting, and participants

A cohort of 1021 patients underwent restaging transurethral resection for high-risk (Ta, T1, Tis) bladder cancer.

Intervention

Patients received a 6-wk induction course of BCG therapy. Responding patients did not receive maintenance BCG. Relapsing patients were eligible for retreatment with BCG. All patients were followed for a minimum of 5 yr.

Measurements

End points were 5-yr tumor- and progression-free survival rates.

Results and limitations

Of 816 complete responders to induction BCG, 2- and 5-yr recurrence-free survival rates were 73% and 46%, respectively. The progression-free survival rate was 89%. Progression-free survival time was 56 mo (95% confidence interval, 55-58 mo). Thirty-two percent of the patients required another course of BCG therapy. We cannot exclude that maintenance BCG may benefit patients beyond 5 yr over induction BCG alone and selective BCG retreatments.

Conclusions

Our results with BCG treatment without maintenance of patients with high-risk non-muscle-invasive bladder cancer compare favorably with trials in which comparable patients received maintenance BCG.     

Diagnosis of breast cancer in women age 40 and younger: delays in diagnosis result from underuse of genetic testing and breast imaging

Background

The impact of newer breast imaging technologies and genetic testing on the detection of breast cancer in women age 40 and younger remains unknown.

Methods

A records review identified 628 women age 40 and younger diagnosed with breast cancer from 1996 to 2008. Patient and tumor characteristics, means of diagnosis, imaging results, and genetic testing were examined.

Results

Tumors were first detected by self-examination in 71%, with a median invasive tumor size of 2.0 cm. Imaging performed at or after diagnosis visualized most tumors; mammography visualized 86%, magnetic resonance imaging (MRI) visualized 96%, and mammography plus MRI visualized more than 98% of tumors. For 81% of patients, the mammogram at diagnosis was their first mammogram. Although 50% had a family history of breast or ovarian cancer, few underwent genetic testing before their cancer diagnosis; 61 of 247 (25%) ultimately tested had a BRCA mutation.

Conclusions

Better use of genetic testing, mammography, and MRI could improve breast cancer detection in young women.     

Real-time cancer cell tracking by bioluminescence in a preclinical model of human bladder cancer growth and metastasis

Background

Bladder cancer is the fifth most common malignancy in the Western world and the second most frequently diagnosed genitourinary tumor. In the majority of cases, death from bladder cancer results from metastatic disease. Understanding the multistep process of carcinogenesis and metastasis in urothelial cancers is pivotal to the development of new therapeutic strategies. Molecular imaging of cancer growth and metastasis in preclinical models provides the essential link between cell-based experiments and clinical translation.

Objective

Develop preclinical models for sensitive bladder cancer cell tracking during tumor progression and metastasis.

Design, setting, and participants

A human transitional cell carcinoma UM-UC-3 cell line was generated that stably expresses luciferase 2 (UM-UC-3luc2), a mammalian codon-optimized firefly luciferase with superior expression. Preclinical models were developed with human UM-UC-3luc2 cells xenografted into the bladder (orthotopic model with metastases) or inoculated into the left cardiac ventricle (bone metastasis model) of immunocompromised mice.

Measurements

Noninvasive, sensitive bioluminescent imaging of human firefly luciferase 2-positive bladder cancer in mice using the IVIS100 imaging system.

Results and limitations

In the orthotopic model (intravesical inoculation), tumor growth could be followed directly after inoculation of UM-UC-3luc2 cells. Importantly, micrometastatic lesions originating from orthotopically implanted cancer cells could be detected in the locoregional lymph nodes and in distant organs. In addition, the superior bioluminescent indicator firefly luciferase 2 allows the detection and monitoring of micrometastatic lesions in real time after intracardiac inoculation of human bladder cancer cells in mice. The main disadvantage is the lack of T-cell immunity in the preclinical models.

Conclusions

The new bioluminescence-based preclinical bladder cancer models enable superior, noninvasive, and real-time tracking of cancer cells, tumor progression, and micrometastasis. Because of the significant improvement in detection of small cell numbers, the presented models are ideally suited for functional studies dealing with minimal residual disease as well as real-time imaging of drug response.     

Polygenic risk score improves prostate cancer risk prediction: results from the Stockholm-1 cohort study

Background

More than 1 million prostate biopsies are conducted yearly in the United States. The low specificity of prostate-specific antigen (PSA) results in diagnostic biopsies in men without prostate cancer (PCa). Additional information, such as genetic markers, could be used to avoid unnecessary biopsies.

Objective

To determine whether single nucleotide polymorphisms (SNPs) associated with PCa can be used to determine whether biopsy of the prostate is necessary.

Design, settings, and participants

The Stockholm-1 cohort (n = 5241) consisted of men who underwent a prostate biopsy during 2005 to 2007. PSA levels were retrieved from databases and family histories were obtained using a questionnaire. Thirty-five validated SNPs were analysed and converted into a genetic risk score that was implemented in a risk-prediction model.

Results and limitations

When comparing the nongenetic model (based on age, PSA, free-to-total PSA, and family history) with the genetic model and using a fixed number of detected PCa cases, it was found that the genetic model required significantly fewer biopsies than the nongenetic model, with 480 biopsies (22.7%) avoided, at a cost of missing a PCa diagnosis in 3% of patients characterised as having an aggressive disease. However, the overall genetic model does not discriminate between aggressive and nonaggressive cases.

Conclusion

Although the genetic model reduced the number of biopsies more than the nongenetic model, the clinical significance of this finding requires further evaluation.     

Combined Ultrasmall Superparamagnetic Particles of Iron Oxide–Enhanced and Diffusion-weighted Magnetic Resonance Imaging Facilitates Detection of Metastases in Normal-sized Pelvic Lymph Nodes of Patients with Bladder and Prostate Cancer

Background

Conventional cross-sectional imaging with computed tomography and magnetic resonance imaging (MRI) has limited accuracy for lymph node (LN) staging in bladder and prostate cancer patients.

Objective

To prospectively assess the diagnostic accuracy of combined ultrasmall superparamagnetic particles of iron oxide (USPIO) MRI and diffusion-weighted (DW) MRI in staging of normal-sized pelvic LNs in bladder and/or prostate cancer patients.

Design, setting, and participants

Examinations with 3-Tesla MRI 24–36 h after administration of USPIO using conventional MRI sequences combined with DW-MRI (USPIO-DW-MRI) were performed in 75 patients with clinically localised bladder and/or prostate cancer staged previously as N0 by conventional cross-sectional imaging. Combined USPIO-DW-MRI findings were analysed by three independent readers and correlated with histopathologic LN findings after extended pelvic LN dissection (PLND) and resection of primary tumours.

Outcome measurements and statistical analysis

Sensitivity and specificity for LN status of combined USPIO-DW-MRI versus histopathologic findings were evaluated per patient (primary end point) and per pelvic side (secondary end point). Time required for combined USPIO-DW-MRI reading was assessed.

Results and limitations

At histopathologic analysis, 2993 LNs (median: 39 LNs; range: 17–68 LNs per patient) with 54 LN metastases (1.8%) were found in 20 of 75 (27%) patients. Per-patient sensitivity and specificity for detection of LN metastases by the three readers ranged from 65% to 75% and 93% to 96%, respectively; sensitivity and specificity per pelvic side ranged from 58% to 67% and 94% to 97%, respectively. Median reading time for the combined USPIO-DW-MRI images was 9 min (range: 3–26 min). A potential limitation is the absence of a node-to-node correlation of combined USPIO-DW-MRI and histopathologic analysis.

Conclusions

Combined USPIO-DW-MRI improves detection of metastases in normal-sized pelvic LNs of bladder and/or prostate cancer patients in a short reading time.This trial is registered with ClinicalTrials.gov (identifier NCT00622973).     

The role of abiraterone acetate in the management of prostate cancer: a critical analysis of the literature

Context

The development of agents targeting androgen signalling holds promise for men with castration-resistant prostate cancer (CRPC).

Objective

The emerging role of abiraterone acetate (AA), a novel, orally administered androgen synthesis inhibitor, is critically analysed.

Evidence acquisition

Data were acquired from critically important original research published in peer-reviewed literature or presented at conferences conducted by the American Society of Clinical Oncology and the European Society of Medical Oncology.

Evidence synthesis

The major findings are addressed in an evidence-based, objective, and balanced fashion.

Conclusions

AA specifically inhibits CYP17 and substantially reduces serum androgen levels without inducing significant adrenal insufficiency. A phase 3 trial reported a significant extension of survival in metastatic CRPC with AA plus prednisone compared to prednisone alone following docetaxel. The primary toxicity of mineralocorticoid excess is manageable. The addition of low-dose corticosteroids to AA may be necessary for controlling symptoms of mineralocorticoid excess.     

Applicability of robot-assisted laparoscopic radical prostatectomy in renal allograft recipients

Purpose

To evaluate the general applicability of robotic-assisted laparoscopic radical prostatectomy (RALP) in renal transplant recipients and potential surgical modifications due to the position of the transplanted kidney in the iliac fossa, as RALP has proven to be an effective and safe treatment option for prostate cancer (PCa) removal.

Procedures

A 71-year-old patient who had undergone renal transplantation was diagnosed with biopsy-proven localized Gleason 7a PCa. The prostate-specific antigen value was 12.4 ng/mL. RALP was performed by a transperitoneal approach using six ports. By partial mobilization of the bladder, the working space for the radical prostatectomy was created, while leaving the renal transplant and ureter untouched. Lymph node dissection was performed only on the contralateral side of the transplanted kidney.

Results

The procedure concluded after 220 minutes and the estimated blood loss was 300 mL. The perioperative clinical course was uneventful. The kidney function remained normal with a creatinine value of 1.2 mg/dL. A complete extirpation of the prostate with negative surgical margins was achieved. After catheter removal, the patient was completely continent.

Conclusions

RALP in renal transplant recipients is feasible and can be achieved with favorable oncological and functional outcome. No modifications to the standard RALP technique are required in these patients, except from a partial dissection of the bladder from the abdominal wall and a one-sided lymph node dissection.     

Clinical nodal staging scores for bladder cancer: a proposal for preoperative risk assessment

Background

Radical cystectomy (RC) with pelvic lymph node dissection (LND) is the standard of care for refractory non-muscle-invasive and muscle-invasive bladder cancer. Although consensus exists on the need for LND, its extent is still debated.

Objective

To develop a model that allows preoperative determination of the minimum number of lymph nodes (LNs) needed to be removed at RC to ensure true nodal status.

Design, setting, and participants

We analyzed data from 4335 patients treated with RC and pelvic LND without neoadjuvant chemotherapy at 12 academic centers located in the United States, Canada, and Europe.

Measurements

We estimated the sensitivity of pathologic nodal staging using a beta-binomial model and developed clinical (preoperative) nodal staging scores (cNSS), which represent the probability that a patient has LN metastasis as a function of the number of examined nodes.

Results and limitations

The probability of missing a positive LN decreased with an increasing number of nodes examined (52% if 3 nodes were examined, 40% if 5 were examined, and 26% if 10 were examined). A cNSS of 90% was achieved by examining 6 nodes for clinical Ta-Tis tumors, 9 nodes for cT1 tumors, and 25 nodes for cT2 tumors. In contrast, examination of 25 nodes provided only 77% cNSS for cT3-T4 tumors. The study is limited due to its retrospective design, its multicenter nature, and a lack of preoperative staging parameters.

Conclusions

Every patient treated with RC for bladder cancer needs an LND to ensure accurate nodal staging. The minimum number of examined LNs for adequate staging depends preoperatively on the clinical T stage. Predictive tools can give a preoperative estimation of the likelihood of nodal metastasis and thereby allow tailored decision-making regarding the extent of LND at RC.     

Late gastrointestinal toxicities following radiation therapy for prostate cancer

Background

Radiation therapy is commonly used to treat localized prostate cancer; however, representative data regarding treatment-related toxicities compared with conservative management are sparse.

Objective

To evaluate gastrointestinal (GI) toxicities in men treated with either primary radiation or conservative management for T1-T2 prostate cancer.

Design, setting, and participants

We performed a population-based cohort study, using Medicare claims data linked to the Surveillance Epidemiology and End Results data. Competing risk models were used to evaluate the risks.

Measurements

GI toxicities requiring interventional procedures occurring at least 6 mo after cancer diagnosis.

Results and limitations

Among 41 737 patients in this study, 28 088 patients received radiation therapy. The most common GI toxicity was GI bleeding or ulceration. GI toxicity rates were 9.3 per 1000 person-years after three-dimensional conformal radiotherapy, 8.9 per 1000 person-years after intensity-modulated radiotherapy, 5.3 per 1000 person-years after brachytherapy alone, 20.1 per 1000 person-years after proton therapy, and 2.1 per 1000 person-years for conservative management patients. Radiation therapy is the most significant factor associated with an increased risk of GI toxicities (hazard ratio [HR]: 4.74; 95% confidence interval [CI], 3.97-5.66). Even after 5 yr, the radiation group continued to experience significantly higher rates of new GI toxicities than the conservative management group (HR: 3.01; 95% CI, 2.06-4.39). Because our cohort of patients were between 66 and 85 yr of age, these results may not be applicable to younger patients.

Conclusions

Patients treated with radiation therapy are more likely to have procedural interventions for GI toxicities than patients with conservative management, and the elevated risk persists beyond 5 yr.     

Surgical treatment in Paget's disease of the breast

Background

The aim of this study was to evaluate the outcomes of surgical treatment of Paget's disease of the breast, with special emphasis on magnetic resonance imaging (MRI) and sentinel node biopsy (SNB).

Methods

The study included 58 consecutive patients with Paget's disease treated from 1995 to 2006.

Results

Twenty-five patients had ductal carcinoma in situ, and 31 had invasive carcinoma. MRI was performed in 14 patients, with positive findings in 7 patients, 5 of whom had negative findings on conventional imaging. The overall mastectomy rate was 76%. Eighteen patients underwent SNB, and 26 patients underwent full or partial axillary clearance. Fourteen patients had no axillary surgery. One patient had local recurrence after breast conservation, and another had axillary recurrence after negative results on SNB. Six patients had distant metastases. Four patients died of breast cancer.

Conclusions

Paget's disease is frequently associated with peripheral or multicentric cancer. MRI may be helpful when considering breast conservation or omitting axillary nodal staging.     

Intraoperative laparoscopic fluorescence guidance to the sentinel lymph node in prostate cancer patients: clinical proof of concept of an integrated functional imaging approach using a multimodal tracer

Background

Integration of molecular imaging and in particular intraoperative image guidance is expected to improve the surgical accuracy of laparoscopic lymph node (LN) dissection.

Objective

To show the applicability of combining preoperative, intraoperative, and postoperative sentinel node imaging using an integrated diagnostic approach based on an imaging agent that is both radioactive and fluorescent.

Design, setting, and participants

Before surgery, multimodal indocyanine green (ICG)-^99mTc-NanoColl was injected into the prostate. Subsequent lymphoscintigraphy and single-photon emission computed tomography/computed tomography (SPECT/CT) imaging of pelvic nodes was performed to determine the location of the sentinel lymph nodes (SLNs) preoperatively. During the surgical procedure a fluorescence laparoscope, optimized for detection in the near infrared range, was used to visualize the nodes identified on SPECT/CT. Eleven patients scheduled for robot-assisted laparoscopic prostatectomy (RALP) with an increased risk of nodal metastasis, based on Memorial Sloan-Kettering Cancer Center/Kattan nomogram estimation, participated in a pilot assessment (N09IGF).

Surgical procedure

Patients underwent RALP with LN dissection for prostate cancer.

Measurements

Radioactive and fluorescent signals were monitored using different modalities, and the correlation between the two types of signals was studied. The location of preoperatively detected SLNs was documented.

Results and limitations

Preoperatively, SLNs were identified by SPECT/CT, and the multimodal nature of the imaging agent also enabled intraoperative detection via fluorescence imaging. Fluorescence particularly improved surgical guidance in areas with a high radioactive background signal such as the injection site. Ex vivo analysis revealed a strong correlation between the radioactive and fluorescent content in the excised LNs. Fluorescence detection is limited by the severe tissue attenuation of the signal. Therefore, radio guidance to the areas of interest is still desirable.

Conclusions

Initial data indicate that multimodal ICG-^99mTc-NanoColloid, in combination with a laparoscopic fluorescence laparoscope, can be used to facilitate and optimize dissection of SLNs during RALP procedures.     

Hepatocellular Carcinoma in Kidney Transplant Recipients

Objective

A kidney transplant is a suitable surgical management for end-stage renal disease patients; however, posttransplantation malignancy is an unwanted outcome. In Taiwan, hepatocellular carcinoma (HCC) is a major malignancy not only among the general population but also in the post-kidney transplant group. Therefore, regular imaging studies for posttransplantation follow-up are necessary. We examined the imaging characteristics and the efficacy of radiologic diagnostic criteria and the American Joint Committee on Cancer (AJCC) staging system in post-kidney transplantation HCC.

Patients and Methods

We retrospectively reviewed 15 patients with post-transplantation HCC among 554 hospital-based kidney transplant recipients. From 1988 to 2008 we analyzed the patient profiles, imaging studies, histopathologic diagnosis, treatment methods, and outcomes. The 6th-edition AJCC radiologic staging system was applied for validation in this study.

Results

Using the AJCC staging system, all 15 patients with histopathologically confirmed HCC were enrolled as stage I (n = 7), stage II (n = 2), stage IIIA (n = 5), or stage IV (n = 1) cases. The 5-year survival rates were 71.4% in stage I, 50% in stage II, 20% in stage IIIA, and 0% in stage IV. Over one-half of post-kidney transplantation HCC were sized 2.5-6.0 cm in diameter with mixed echogenicity. The positive diagnostic rate for radiologic criteria was 83.3%.

Conclusions

The AJCC staging system and the radiologic diagnostic criteria were validated in post-kidney transplantation HCC. Surgical resection and transcatheter arterial embolization for early-stage HCC in kidney transplant recipients showed satisfactory outcomes. A noncirrhotic liver in a kidney transplant recipient makes surgical resection the treatment of choice because of the better prognosis.     

Neoadjuvant pegylated liposomal doxorubicin in combination with cisplatin and infusional fluoruracil (CCF) with and without endocrine therapy in locally advanced primary or recurrent breast cancer

Purpose

To explore the activity of pegylated liposomal doxorubicin (PLD) as neoadjuvant therapy of breast cancer.

Methods

The combination of PLD with cisplatin and infusional fluorouracil (CCF) for 8 courses was investigated in patients with primary or recurrent T2-T4a-d N0-3 M0 breast cancer. Patients with ER and/or PgR ≥10% tumors also received letrozole (±triptorelin).

Results

Forty patients entered the study. Four patients had recurrent tumors and 13 had cT4d tumors. Overall, clinical response rate was 77.5% whereas a pathological complete response (pCR) was obtained in 3 patients (7.7%), 4 when considering bilateral tumors. Noticeably 3 pCR were observed among the 10 patients with T4d ER positive tumors (33%). Eleven patients discontinued treatment before completion of the 8 planned courses.

Conclusions

Our results indicated that CCF yielded an appreciable rate of clinical responses in a series of very locally advanced tumors and an unusually high rate of pCR in T4d ER positive tumors, suggesting an enhanced cutaneous activity of PLD.     

Familial renal cell carcinoma from the Swedish Family-Cancer Database

Background

Reliable data on familial risks are important for clinical counselling and cancer genetics.

Objective

To evaluate familial risks for renal cell carcinomas (RCC) through parental and sibling probands in the largest available dataset.

Design, setting, and participants

This study examined the Swedish Family-Cancer Database on 12.2 million individuals, which contains families with parents and offspring. Cancer data were retrieved from the Swedish Cancer Registry for the years 1961-2008, including 8513 patients with RCC.

Measurements

Familial risk for offspring was defined through standardised incidence ratios (SIRs) and adjusted for many variables, including a proxy for smoking and obesity.

Results and limitations

The familial risk for RCCs was 1.75 when a parent and 2.61 when a sibling was diagnosed with any kidney cancer. Also, RCCs were shown to be associated with prostate cancer (PCa) when parents or parents and siblings were diagnosed with PCa. Among siblings, the associations of RCC with melanoma, non-Hodgkin's lymphoma, and urinary bladder and papillary thyroid tumours were found. None of the results differed significantly after excluding the families with cancer pathognomonic of a von Hippel-Lindau (VHL) disease. Limitations of this study include the small number of familial cases (229 familial cases).

Conclusions

The present analysis showed a high familiarity for RCC, and recessive effects may be important for familial aggregation of RCC. As a novel association, offspring RCC was in excess when parents or parents and siblings were diagnosed with PCa. There is familial clustering beyond VHL and the recent low-risk gene that probably explains a small proportion of the observed familial clustering.     

Active surveillance of small renal masses: progression patterns of early stage kidney cancer

Background

Most early stage kidney cancers are renal cell carcinomas (RCCs), and most are diagnosed incidentally by imaging as small renal masses (SRMs). Indirect evidence suggests that most small RCCs grow slowly and rarely metastasize.

Objective

To determine the progression and growth rates for newly diagnosed SRMs stratified by needle core biopsy pathology.

Design, setting, and participants

A multicenter prospective phase 2 clinical trial of active surveillance of 209 SRMs in 178 elderly and/or infirm patients was conducted from 2004 until 2009 with treatment delayed until progression.

Intervention

Patients underwent serial imaging and needle core biopsies.

Measurements

We measured rates of change in tumor diameter (growth measured by imaging) and progression to ≥4 cm, doubling of tumor volume, or metastasis with histology on biopsy.

Results and limitations

Local progression occurred in 25 patients (12%), plus 2 progressed with metastases (1.1%). Of the 178 subjects with 209 SRMs, 127 with 151 SRMs had > 12 mo of follow-up with two or more images, with a mean follow-up of 28 mo. Their tumor diameters increased by an average of 0.13 cm/yr. Needle core biopsy in 101 SRMs demonstrated that the presence of RCC did not significantly change growth rate. Limitations included no central review of imaging and pathology and a short follow-up.

Conclusions

This is the first SRM active surveillance study to correlate growth with histology prospectively. In the first 2 yr, the rate of local progression to higher stage is low, and metastases are rare. SRMs appear to grow very slowly, even if biopsy proven to be RCC. Many patients with SRMs can therefore be initially managed conservatively with serial imaging, avoiding the morbidity of surgical or ablative treatment.     

Trends in mortality from urologic cancers in Europe, 1970-2008

Background

In recent decades, there have been substantial changes in mortality from urologic cancers in Europe.

Objective

To provide updated information, we analyzed trends in mortality from cancer of the prostate, testis, bladder, and kidney in Europe from 1970 to 2008.

Design, setting, and participants

We derived data for 33 European countries from the World Health Organization database.

Measurements

We computed world-standardized mortality rates and used joinpoint regression to identify significant changes in trends.

Results and limitations

Mortality from prostate cancer has leveled off since the 1990 s in countries of western and northern Europe, particularly over the last few years while it was still rising in Bulgaria, Romania, and Russia. In the European Union (EU), it reached a peak in 1995 at 15.0 per 100 000 men and declined to 12.5 per 100 000 in 2006. Mortality from testicular cancer has steadily declined in most countries in western and northern Europe since the 1970 s. The declines were later and appreciably lower in central/eastern Europe. In EU, rates declined from 0.75 in 1980 to 0.32 per 100 000 men in 2006, with stronger declines up to the late 1990 s and an apparent leveling off in rates thereafter. Over the last 15 years, mortality from bladder cancer has declined in most European countries in both sexes. The major exceptions were Bulgaria, Poland, and Romania. In the EU, bladder cancer mortality was stable until 1992 and declined thereafter from 7.3 to 5.5 per 100 000 men and from 1.5 to 1.2 per 100 000 women in 2006. Mortality from kidney cancer increased throughout Europe until the early 1990 s and leveled off thereafter in many countries, except in a few central and eastern ones. Between 1994 and 2006, rates declined from 4.9 to 4.3 per 100 000 in EU men and from 2.1 to 1.8 per 100 000 in EU women.

Conclusions

Over the last two decades, trends in urologic cancer mortality were favorable in Europe, with the exception of a few central and eastern countries.     

Breastfeeding and prognostic markers in breast cancer

Background

Several studies suggest that total breastfeeding time reduces breast cancer risk. The underlying mechanisms are unclear. Whether breastfeeding also affects the prognosis is not yet investigated. A number of tumour characteristics, i.e. histological type of cancer, grade, tumour size, Nottingham prognostic index, vascular invasion and DNA-ploidy, have been demonstrated to be of prognostic value.

Methods

We have searched for a possible link between these prognostic markers and breastfeeding time, age at first child and number of children. 250 women treated for breast cancer have answered a questionnaire.

Results

No significant interactions were found possibly with one exception, LVI vs. age at first child. We found, significant correlations between lobular cancer, and thereby also DNA-ploidy, and age at first childbirth.

Conclusions

We have found that lobular cancer (and thereby also diploid tumours) are connected, independently, to age at first childbirth and possibly also to number of children but no other correlations between reproductive data, breastfeeding included, and prognostic markers used in this study were found.