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).     

Three–Axillary Lymph Node Sampling for the Prediction of Nonsentinel Node Metastases in Breast Cancer Patients With Sentinel Node Metastases

Background In half of breast cancer patients with positive sentinel nodes, the sentinel nodes are the only metastatic nodes. Such patients have no more metastatic nonsentinel nodes and do not need to undergo axillary lymph node dissection. The purpose of this study was to investigate whether three–axillary lymph node sampling after sentinel node biopsy predicts the status of nonsentinel nodes in patients with sentinel node metastases. Methods Sentinel node biopsy was performed with dye and radioisotope. When the sentinel nodes were diagnosed as metastasis positive by using intraoperative imprint cytology, three–axillary lymph node sampling was performed, followed by axillary lymph node dissection. Results Of 47 cases with positive imprint cytology, 43 (91%) were diagnosed as metastasis positive on their final histological examination and were analyzed. The status of the sampled nodes was significantly associated with the status of nonsentinel nodes (P < .0001). Six (43%) of 14 patients with positive sampled nodes had at least 1 positive remaining node. Only 2 (7%) of 29 patients whose sampled nodes were negative were found to have additional nodal metastases. The sensitivity, specificity, and accuracy of the sampled nodes for the prediction of nonsentinel node metastases were 87.5%, 100%, and 95.3%, respectively. Conclusions We demonstrated that three-node sampling may be useful for predicting the status of nonsentinel nodes and avoiding axillary lymph node dissection in patients with only sentinel node metastases.     

The Key Combined Value of Multiparametric Magnetic Resonance Imaging,and Magnetic Resonance Imaging–targeted and Concomitant Systematic Biopsies for the Prediction of Adverse Pathological Features in Prostate Cancer Patients Undergoing Radical Prostatectomy

BackgroundThe combined role of multiparametric magnetic resonance imaging (mp-MRI), and magnetic resonance imaging (MRI)-targeted and concomitant systematic biopsies in the identification of prostate cancer (PCa) patients at a higher risk of adverse pathology at radical prostatectomy (RP) is still unclear.ObjectiveTo develop novel models to predict extracapsular extension (ECE), seminal vesicle invasion (SVI), or upgrading in patients diagnosed with MRI-targeted and concomitant systematic biopsies.Design, setting, and participantsWe included 614 men with clinical stage ≤ T2 at digital rectal examination who underwent MRI-targeted biopsy with concomitant systematic biopsy.Outcome measurements and statistical analysesLogistic regression analyses predicting ECE, SVI, and upgrading (ie, a shift from biopsy International Society of Urological Pathology grade group to any higher grade at RP) based on clinical variables with or without mp-MRI features and systematic biopsy information (the percentage of cores with grade group ≥2 PCa) were developed and internally validated. The area under the curve (AUC) was used to identify the models with the highest discrimination. Decision-curve analyses (DCAs) determined the net benefit associated with their use.Results and limitationsOverall, 333 (54%), 88 (14%), and 169 (27%) patients had ECE, SVI, and upgrading at RP, respectively. The inclusion of mp-MRI data improved the discrimination of clinical models for ECE (67% vs 70%) and SVI (74% vs 76%). Models including mp-MRI, and MRI-targeted and concomitant systematic biopsy information achieved the highest AUC at internal validation for ECE (73%), SVI (81%), and upgrading (73%) and represented the basis for three risk calculators that yield the highest net benefit at DCA.ConclusionsNot only mp-MRI and MRI-targeted sampling, but also concomitant systematic biopsies provide significant information to identify patients at a higher risk of adverse pathology. Although omitting systematic prostate sampling at the time of MRI-targeted biopsy might be associated with a reduced risk of detecting insignificant PCa and lower patient discomfort, it reduces the ability to accurately predict pathological features.Patient summaryThe combination of multiparametric magnetic resonance imaging (mp-MRI) with accurate biopsy information on MRI-targeted and systematic biopsies improves the accuracy of multivariable models based on clinical and mp-MRI data alone. Correct mp-MRI interpretation and proper extensive prostate sampling are both needed to predict adverse pathology accurately at radical prostatectomy.     

Association Between the Number of Dissected Lymph Nodes During Pelvic Lymphadenectomy and Cancer-Specific Survival in Patients with Lymph Node–Negative Urothelial Carcinoma of the Bladder Undergoing Radical Cystectomy

Background

A larger number of dissected lymph nodes (LN) during pelvic lymphadenectomy in patients with muscle-invasive transitional-cell carcinoma of the bladder treated by radical cystectomy (RC) is crucial for exact tumor staging and is associated with a positive oncological outcome.

Methods

Clinical and pathological records of 1291 patients undergoing RC due to LN-negative transitional-cell carcinoma of the bladder were summarized and evaluated in a multi-institutional database. The number of removed LNs and the presence or absence of lymphovascular invasion were assessed. On the basis of multivariate Cox regression analyses, a threshold number of removed LNs was defined that exerted an independent influence on cancer-specific survival (CSS).

Results

In multivariate Cox regression models for different numbers of removed LNs, a statistically significant enhancement of CSS could be demonstrated for a LN count of 16. Furthermore, the integration of the dichotomized LN count of 16 resulted in a statistically significantly enhanced predictive ability of the model for CSS. Patients with <16 and ≥16 removed LNs showed CSS rates after 5 years of 72% and 83%, respectively (P = 0.01). In addition, age, sex, pT stage, and lymphovascular invasion had independent influences on CSS in every Cox regression model.

Conclusions

In patients undergoing RC, removal of a higher LN count is associated with an improved oncological outcome. The information resulting from an assessment of lymphovascular invasion and an extended lymphadenectomy is critical for stratification of risk groups and identification of patients who might benefit from adjuvant treatment.

     

Can Whole-body Magnetic Resonance Imaging with Diffusion-weighted Imaging Replace Tc 99m Bone Scanning and Computed Tomography for Single-step Detection of Metastases in Patients with High-risk Prostate Cancer?

Background

Technetium Tc 99m bone scintigraphy (BS) and contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) of the pelvis and abdomen are universally recommended for detecting prostate cancer (PCa) metastases in cancer of all stages. However, this two-step approach has limited sensitivity and specificity.

Objective

Evaluate the diagnostic accuracy of whole-body MRI (WBMRI) as a one-step screening test for PCa metastases.

Design, setting, and participants

One hundred consecutive PCa patients at high risk for metastases prospectively underwent WBMRI, CT, and BS completed with targeted x-rays (BS/TXR) in case of equivocal BS. Four independent reviewers reviewed the images.

Measurements

This study compares the diagnostic performance of WBMRI, CT, BS, and BS/TXR in detecting PCa metastases using area under the curve (AUC) receiver operator characteristics. A best valuable comparator (BVC) approach was used to adjudicate final metastatic status in the absence of pathologic evaluation.

Results and limitations

Based on the BVC, 68 patients had metastases. The sensitivity of BS/TXR and WBMRI for detecting bone metastases was 86% and 98–100%, respectively (p < 0.04), and specificity was 98% and 98–100%, respectively. The first and second WBMRI readers respectively identified bone metastases in 7 and 8 of 55 patients with negative BS/TXR. The sensitivity of CT and WBMRI for detecting enlarged lymph nodes was similar, at 77–82% for both; specificity was 95–96% and 96–98%, respectively. The sensitivity of the combination of BS/TXR plus CT and WBMRI for detecting bone metastases and/or enlarged lymph nodes was 84% and 91–94%, respectively (p = 0.03–0.10); specificities were 94–97% and 91–96%, respectively. The 95% confidence interval of the difference between the AUC of the worst WBMRI reading and the AUC of any of the BS/TXR plus CT lay within the noninferiority margin of ±10% AUC.

Conclusions

WBMRI outperforms BS/TXR in detecting bone metastases and performs as well as CT for enlarged lymph node evaluation. WBMRI can replace the current multimodality metastatic work-up for the concurrent evaluation of bones and lymph nodes in high-risk PCa patients.     

Characteristics of Prostate Cancer Found at Fifth Screening in the European Randomized Study of Screening for Prostate Cancer Rotterdam: Can We Selectively Detect High-grade Prostate Cancer with Upfront Multivariable Risk Stratification and Magnetic Resonance Imaging?

Background

The harm of screening (unnecessary biopsies and overdiagnosis) generally outweighs the benefit of reducing prostate cancer (PCa) mortality in men aged ≥70 yr. Patient selection for biopsy using risk stratification and magnetic resonance imaging (MRI) may improve this benefit-to-harm ratio.

External Validation of a Multiparametric Magnetic Resonance Imaging–based Nomogram for the Prediction of Extracapsular Extension and Seminal Vesicle Invasion in Prostate Cancer Patients Undergoing Radical Prostatectomy

The nomogram reported by Gandaglia et al (The key combined value of multiparametric magnetic resonance imaging, and magnetic resonance imaging-targeted and concomitant systematic biopsies for the prediction of adverse pathological features in prostate cancer patients undergoing radical prostatectomy. Eur Urol 2020;77:733–41) predicting extracapsular extension (ECE) or seminal vesicle invasion (SVI) has been developed using multiparametric magnetic resonance imaging (MRI) parameters and MRI-targeted biopsy. We aimed to validate this nomogram externally by analyzing 566 patients harboring prostate cancer diagnosed on MRI-targeted biopsy followed by radical prostatectomy. At final pathology, 37% and 12% patients had ECE and SVI, respectively. Performance of the nomogram, in comparison with the Memorial Sloan Kettering Cancer Center (MSKCC) model and Partin tables, was evaluated using discrimination, calibration, and decision curve analysis. Regarding ECE prediction, the nomogram showed higher discrimination (71.8% vs 69.8%, p = 0.3 and 71.8% vs 61.3%, p < 0.001), and similar miscalibration and net benefit for probability threshold above 30% when compared with MSKCC model and Partin tables, respectively. Performance of the nomogram with regard to SVI was comparable in terms of discrimination (68.5% vs 70.4% vs 67.8%, p ≥ 0.6), presenting a slight overestimation on calibration plots and a net benefit for probability threshold above 7.5%. This is the first multicentric study that externally validates a nomogram predicting ECE and SVI in patients diagnosed with MRI-targeted biopsy. Its performance was less optimistic than expected, and implementation of MRI in this setting was not associated with a clear improvement in patient selection and clinical usefulness when compared with available models. We proposed an updated version of the nomogram predicting ECE using the recalibration method, which leads to an improvement in its performance and needs to be validated in another external set.Patient summaryWe validate a prediction tool based on multiparametric magnetic resonance imaging (MRI) parameters and MRI-targeted biopsy predicting extracapsular extension and seminal vesicle invasion at radical prostatectomy. An improvement of patient selection was not clearly demonstrated when compared with available models based on clinical parameters, and implementation of MRI in this setting still needs to be clarified.     

Cohort Study of Oligorecurrent Prostate Cancer Patients: Oncological Outcomes of Patients Treated with Salvage Lymph Node Dissection via Prostate-specific Membrane Antigen–radioguided Surgery

BackgroundIn a subset of patients with recurrent oligometastatic prostate cancer (PCa) salvage surgery with prostate-specific membrane antigen (PSMA)-targeted radioguidance (PSMA-RGS) might be of value.ObjectiveTo evaluate the oncological outcomes of salvage PSMA-RGS and determine the predictive preoperative factors of improved outcomes.Design, setting, and participantsA cohort study of oligorecurrent PCa patients with biochemical recurrence (BCR) after radical prostatectomy and imaging with PSMA positron emission tomography (PET), treated with PSMA-RGS in two tertiary care centers (2014–2020), was conducted.InterventionPSMA-RGS.Outcome measurements and statistical analysisKaplan-Meier and multivariable Cox regression models were used to assess BCR-free (BFS) and therapy-free (TFS) survival. Postoperative complications were classified according to Clavien-Dindo.Results and limitationsOverall, 364 patients without concomitant treatment were assessed. At PSMA-RGS, metastatic soft-tissue PCa lesions were removed in 343 (94%) patients. At 2–16 wk after PSMA-RGS, 165 patients reached a prostate-specific antigen (PSA) level of <0.2 ng/ml. Within 3 mo, 24 (6.6%) patients suffered from Clavien-Dindo complications grade III–IV. At 2 yr, BFS and TFS rates were 32% and 58%, respectively. In multivariable analyses, higher preoperative PSA (hazard ratio [HR]: 1.07, 95% confidence interval [CI]: 1.02–1.12), higher number of PSMA-avid lesions (HR: 1.23, CI: 1.08–1.40), multiple (pelvic plus retroperitoneal) localizations (HR: 1.90, CI: 1.23–2.95), and retroperitoneal localization (HR: 2.04, CI: 1.31–3.18) of lesions in preoperative imaging were independent predictors of BCR after PSMA-RGS. The main limitation is the lack of a control group.ConclusionsAs salvage surgery in oligorecurrent PCa currently constitutes an experimental treatment approach, careful patient selection is mandatory based on life expectancy, low PSA values, and low number of PSMA PET–avid lesions located in the pelvis.Patient summaryWe looked at the outcomes from prostate cancer patients with recurrent disease after radical prostatectomy. We found that surgery may be an opportunity to prolong treatment-free survival, but patient selection criteria need to be very narrow.     

The Role of Radical Prostatectomy and Lymph Node Dissection in Lymph Node–Positive Prostate Cancer: A Systematic Review of the Literature

Context

Because pelvic lymph node (LN)-positive prostate cancer (PCa) is generally considered a regionally metastatic disease, surgery needs to be better defined.

Objective

To review the impact of radical prostatectomy (RP) and pelvic lymph node dissection (PLND), possibly in conjunction with a multimodal approach using local radiotherapy and/or androgen-deprivation therapy (ADT), in LN-positive PCa.

Evidence acquisition

A systematic Medline search for studies reporting on treatment regimens and outcomes in patients with LN-positive PCa undergoing RP between 1993 and 2012 was performed.

Evidence synthesis

RP can improve progression-free and overall survival in LN-positive PCa, although there is a lack of high-level evidence. Therefore, the former practice of aborting surgery in the presence of positive nodes might no longer be supported by current evidence, especially in those patients with a limited LN tumor burden. Current data demonstrate that the lymphatic spread takes an ascending pathway from the pelvis to the retroperitoneum, in which the internal and the common iliac nodes represent critical landmarks in the metastatic distribution. Sophisticated imaging technologies are still under investigation to improve the prediction of LN-positive PCa. Nonetheless, extended PLND including the common iliac arteries should be offered to intermediate- and high-risk patients to improve nodal staging with a possible benefit in prostate-specific antigen progression-free survival by removing significant metastatic load. Adjuvant ADT has the potential to improve overall survival after RP; the therapeutic role of a trimodal approach with adjuvant local radiotherapy awaits further elucidation. Age is a critical parameter for survival because cancer-specific mortality exceeds overall mortality in younger patients (<60 yr) with high-risk PCa and should be an impetus to treat as thoroughly as possible.

Conclusions

Increasing evidence suggests that RP and extended PLND improve survival in LN-positive PCa. Our understanding of surgery of the primary tumor in LN-positive PCa needs a conceptual change from a palliative option to the first step in a multimodal approach with a significant improvement of long-term survival and cure in selected patients.     

Impact of Molecular Subtype on Locoregional Recurrence in Mastectomy Patients with T1–T2 Breast Cancer and 1–3 Positive Lymph Nodes

Background

Postmastectomy radiation (PMRT) in T1–T2 tumors with 1–3 positive axillary lymph nodes (ALNs) is controversial. Impact of molecular subtype (MST) on locoregional recurrence (LRR) and PMRT benefit is uncertain. We examined the association between MST and LRR, recurrence-free survival (RFS), and overall survival (OS), in T1–T2 tumors with 1–3 positive ALNs.

Methods

From an institutional database, we identified mastectomy patients with 1–3 positive ALNs between 1995 and 2006. Patients who received neoadjuvant chemotherapy, had T3–T4 tumors, or ≥4 positive ALNs were excluded. MST was defined as: hormone receptor (HR)+/HER2?(luminal A/B), HR+/HER2+(luminal HER2), HR?/HER2+(HER2), and HR?/HER2?(basal). Kaplan–Meier method and Cox regression analysis were used to examine association between MST and LRR, RFS, and OS.

Results

This study included 884 patients (700 no PMRT, 141 PMRT): 72.8 % luminal A/B, 7.8 % luminal HER2, 6.8 % HER2, and 12.6 % basal. Median follow-up was 6.3 years; 39 LRRs occurred. Luminal A/B subtype had the smallest tumors (p = 0.03), lowest intraductal component (p = 0.01), histologic grade (p < 0.0001), lymphovascular invasion (LVI) (p = 0.008), and multifocality/multicentricity (p = 0.02). On univariate analyses, there was no association between MST and LRR. MST was associated with RFS and OS; the basal and HER2 subtype had the lowest RFS (p = 0.0002) and OS (p < 0.0001). On multivariate analysis, only age ≤50 years (p = 0.003) and presence of LVI (p = 0.0003) were predictive of LRR; MST was not (p = 0.38).

Conclusion

In patients with T1–T2 breast cancer and 1–3 positive lymph nodes who did not receive PMRT, MST was not an independent predictor of LRR and may not be useful in selecting PMRT candidates in that group.     

Negative Prostatic Biopsies in Patients with a High Risk of Prostate Cancer: Is the Combination of Endorectal MRI and Magnetic Resonance Spectroscopy Imaging (MRSI) a Useful Tool? A Preliminary Study

OBJECTIVE: Repeated biopsies in patients with a high risk of prostate cancer only allow a small proportion of new cancer diagnosis. The aim of this study was to evaluate the use of combined MRI and magnetic resonance spectroscopy imaging (MRSI) for these patients. METHODS: Between April 2003 and April 2004, 42 patients with negative multiple cores prostatic biopsies and serum PSA>4 ng/ml underwent a combined MRI/MRSI analysis. Suspicious zones on standard MRI included low intensity signals on T2 weighted images. A high choline+creatine-to-citrate ratio defined a MRSI suspicious zone. A 10 cores following peripheral biopsy scheme was done to which were added supplementary biopsies on the MRI/MRSI suspicious zones. RESULTS: The mean age was 62.3 years (51-74), the mean pre-biopsy serum PSA was 12 (3.87-35), the mean free/total PSA ratio was 11% (5-20). The mean number of previous prostate biopsy rounds was 2.04. 15 prostate cancers were diagnosed (35.7%). In 9 cases, abnormal MRI/MRSI findings and positive biopsy sites were located on the same prostatic zones. In 5 cases, MRSI alone located the positive biopsy zones. Sensitivity of combined MRI/MRSI in this study was 73.3%; specificity, positive predictive value, negative predictive value and accuracy were 96.3%, 91.6%, 86.6% and 88% respectively. CONCLUSIONS: This preliminary study shows that the combination of MRI and MRSI might be able to guide and therefore limit the number of iterative biopsies and cores for patients who are at high risk of having a prostate cancer. In some cases, MRSI alone allows identification of neoplasic prostatic zones. Other studies are needed to confirm these data.     

Cost-effectiveness of Magnetic Resonance (MR) Imaging and MR-guided Targeted Biopsy Versus Systematic Transrectal Ultrasound–Guided Biopsy in Diagnosing Prostate Cancer: A Modelling Study from a Health Care Perspective

Background

The current diagnostic strategy using transrectal ultrasound–guided biopsy (TRUSGB) raises concerns regarding overdiagnosis and overtreatment of prostate cancer (PCa). Interest in integrating multiparametric magnetic resonance imaging (MRI) and magnetic resonance–guided biopsy (MRGB) into the diagnostic pathway to reduce overdiagnosis and improve grading is gaining ground, but it remains uncertain whether this image-based strategy is cost-effective.

Objective

To determine the cost-effectiveness of multiparametric MRI and MRGB compared with TRUSGB.

Design, setting, and participants

A combined decision tree and Markov model for men with elevated prostate-specific antigen (>4 ng/ml) was developed. Input data were derived from systematic literature searches, meta-analyses, and expert opinion.

Outcome measurements and statistical analysis

Quality-adjusted life years (QALYs) and health care costs of both strategies were modelled over 10 yr after initial suspicion of PCa. Probabilistic and threshold analyses were performed to assess uncertainty.

Results and limitations

Despite uncertainty around the presented cost-effectiveness estimates, our results suggest that the MRI strategy is cost-effective compared with the standard of care. Expected costs per patient were €2423 for the MRI strategy and €2392 for the TRUSGB strategy. Corresponding QALYs were higher for the MRI strategy (7.00 versus 6.90), resulting in an incremental cost-effectiveness ratio of €323 per QALY. Threshold analysis revealed that MRI is cost-effective when sensitivity of MRGB is ≥20%. The probability that the MRI strategy is cost-effective is around 80% at willingness to pay thresholds higher than €2000 per QALY.

Conclusions

Total costs of the MRI strategy are almost equal with the standard of care, while reduction of overdiagnosis and overtreatment with the MRI strategy leads to an improvement in quality of life.

Patient summary

We compared costs and quality of life (QoL) of the standard “blind” diagnostic technique with an image-based technique for men with suspicion of prostate cancer. Our results suggest that costs were comparable, with higher QoL for the image-based technique.