Evaluation of the prognostic nutritional index for the prognosis of Chinese patients with high/extremely high-risk prostate cancer after radical prostatectomy

BACKGROUND The incidence of prostate cancer(PCa)is on the rise in China.The risk level of patients with PCa is associated with disease-free survival rate at 10 years after radical prostatectomy.Predicting prognosis in advance according to the degree of risk can provide a reference for patients,especially treatment options and postoperative adjuvant treatment measures for high-risk/extremely high-risk patients.AIM To explore the predictive value of the prognostic nutritional index(PNI)for biological recurrence in Chinese patients with high/extremely high-risk PCa after radical prostatectomy.METHODS The biochemical test results and clinical data of 193 patients who underwent radical prostatectomy for the first time from January 2015 to December 2020 were retrospectively collected.The PNI value of peripheral blood within 1 wk before surgery was calculated,and during the follow-up period,prostate-specific antigen≥0.2 ng/mL was considered to have biological recurrence.The receiver operating characteristic(ROC)curve was used to calculate the optimal critical value and area under the curve(AUC)of the patients.According to the critical value,the progression-free survival of the high PNI group and low PNI group was compared.The independent influencing factors of the patients’prognosis were obtained by the Cox proportional hazards regression model.RESULTS The non-biological recurrence rates at 1,3,and 5 years were 92.02%,84.05%,and 74.85%,respectively.The optimal critical value for PNI to predict biological recurrence was 46.23,and the AUC was 0.789(95%confidence interval:0.651-0.860;P<0.001).The sensitivity and specificity were 82.93%and 62.30%,respectively.In accordance with the optimal critical value of the ROC curve(46.23),193 patients were further divided into a high PNI group(PNI≤46.23,n=108)and low PNI group(PNI>46.23,n=85).The incidence of postoperative complications in the high PNI group was lower than that in the low PNI group(21.18%vs 38.96%).Kaplan-Meier survival analysis showed that the overall survival rate at 5 years in the low PNI group was 87.96%(13/108),which was lower than that in the high PNI group(61.18%,33/85;P<0.05).Low PNI[hazard ratio(HR)=1.74;P=0.003]and positive incisal margin status(HR=2.14;P=0.001)were independent predictors of biological recurrence in patients with high/extremely high-risk PCa.CONCLUSION The PNI has predictive value for the prognosis of patients with high/extremely high-risk PCa,and is an independent prognostic factor.Patients with low PNI value have a shorter time of nonbiological recurrence after prostatectomy.It is expected that the combined prediction of other clinicopathological data will further improve the accuracy and guide postoperative adjuvant therapy to improve the quality of prognosis.

The role of radiotherapy in localised and locally advanced prostate cancer

For a patient suffering from non-metastatic prostate cancer,the individualized recommendation of radiotherapy has to be the fruit of a multidisciplinary approach in the context of a Tumor Board,to be explained carefully to the patient to obtain his informed consent.External beam radiotherapy is now delivered by intensity modulated radiotherapy,considered as the gold standard.From a radiotherapy perspective,low-risk localized prostate cancer is treated by image guided intensity modulated radiotherapy,or brachytherapy if patients meet the required eligibility criteria.Intermediate-risk patients may benefit from intensity modulated radiotherapy combined with 4e6 months of androgen deprivation therapy;intensity modulated radiotherapy alone or combined with brachytherapy can be offered to patients unsuitable for androgen deprivation therapy due to co-morbidities or unwilling to accept it to preserve their sexual health.High-risk prostate cancer,i.e.high-risk localized and locally advanced prostate cancer,requires intensity modulated radiotherapy with long-term(≥2 years)androgen deprivation therapy with luteinizing hormone releasing hormone agonists.Post-operative irradiation,either immediate or early deferred,is proposed to patients classified as pT3pN0,based on surgical margins,prostate-specific antigen values and quality of life.Whatever the techniques and their degree of sophistication,quality assurance plays a major role in the management of radiotherapy,requiring the involvement of physicians,physicists,dosimetrists,radiation technologists and computer scientists.The patients must be informed about the potential morbidity of radiotherapy and androgen deprivation therapy and followed regularly during and after treatment for tertiary prevention and evaluation.A close cooperation is needed with general practitioners and specialists to prevent and mitigate side effects and maintain quality of life.

Outcomes of locally advanced prostate cancer:a single institution study of 209 patients in Japan

Aim： To investigate the outcomes for Asian populations with locally advanced/clinical stage Ⅲ prostate cancer （PCa） treated with currently prevailing modalities. Methods： We reviewed the record of 209 patients with clinical stage Ⅲ PCa, who were treated at Niigata Cancer Center Hospital between 1992 and 2003. Treatment options included hormone therapy-combined radical prostatectomy （RP＋HT）, hormone therapy-combined external beam irradiation （EBRT＋HT） and primary hormone therapy （PHT）. Results： The 5- and 10-year overall survival rates were 80.3% and 46.1% in all cohorts, respectively. The survival rates were 87.3% and 66.5% in the RP＋HT group, 94.9% and 70.0% in the EBRT＋HT group and 66.1% and 17.2% in the PHT group, respectively. A significant survival advantage was found in the EBRT＋HT group compared with that in the PHT group （P 〈 0.0001）. Also, the RP＋HT group had better survival than the PHT group （P = 0.0107）. The 5- and 10-year disease-specific survival rates for all cases were 92.5% and 80.0%, respectively. They were 93.8% and 71.4% in the RP＋HT group, 96.6% and 93.6% in the EBRT＋HT group and 88.6% and 62.3% in the PHT group, respectively. A survival advantage was found in the EBRT＋HT group compared with the PHT group （P = 0.029）. No significant difference was found in disease-specific survival between the EBRT＋HT and RP＋HT groups or between the RP＋HT and PHT groups. Condusion： Although our findings indicate that radiotherapy plus HT has a survival advantage in this stage of PCa, we recommend therapies that take into account the patients＇ social and medical conditions for Asian men with clinical stage Ⅲ PCa.

Long-term effectiveness of luteinizing hormone-releasing hormone agonist or antiandrogen monotherapy in elderly men with localizect prostate cancer （T1-2） ： a retrospective study

Aim： To evaluate the long-term effectiveness, side effects and compliance rates of two types of drugs （luteinizing hormone-releasing hormone [LHRH] agonist and antiandrogen） that were used individually to treat patients with localized prostate cancer （T1-2） at our institution. Methods： Ninety-seven patients who were diagnosed in the period from April 1997 to January 2000 as having clinically localized prostate cancer （T1-2） received either LHRH agonist （leuprolide acetate 7.5 mg/month） monotherapy （group 1, n = 62） or antiandrogen monotherapy （group 2, n = 35; 18 received bicalutamide 50 mg q.d., 13 received nilutamide 150 mg t.i.d, and 4 received flutamide 250 mg t.i.d.）. The mean age in both groups was 76 years. Results： The mean follow-up time was （50.8 ±8.5） months in group 1 and （43.1 ± 2.2） months in group 2. Prostate-specific antigen （PSA） levels rose in only 1 of the 62 patients （1.6%） in group 1, and in 20 of the 35 patients （57.1%） in group 2. In group 2, 10 of the 20 patients （50 %） with increasing PSA levels were treated with LHRH salvage therapy, and eight （80%） responded. Hot flashes （54.8%） and lethargy （41.9%） were the most common side effects in group 1. In contrast, nipple-tenderness （40%） and light-dark adaptation （17.1%） were more often seen in group 2. Only 1 of the 62 patients （1.6%） in group 1 switched to another medication because of adverse side effects; whereas 8 of the 35 patients （22.9%） in group 2 did so. Conclusion： Unlike antiandrogen monotherapy, LHRH agonist monotherapy provided long-term durable control of localized prostate cancer （T1-2）. It can also be an effective treatment option for patients whose disease failed to respond to antiandrogen monotherapy. The limitations of our study are the lack of health outcomes analysis and a small sample size.

Comparison of two adjuvant hormone therapy regimens in patients with high-risk localized prostate cancer after radical prostatectomy, primary results of study CU 1005

The role of adjuvant hormonal therapy and optimized regimens for high-risk localized prostate cancer after radical prostatectomy remains controversial. Herein, the clinical trial CU 1005 prospectively evaluated two regimens of maximum androgen blockage or bicalutamide 150 mg daily as immediate adjuvant therapy for high-risk localized prostate cancer. Overall, 209 consecutive patients were recruited in this study, 107 of whom received 9 months of adjuvant maximum androgen blockage, whereas 102 received 9 months of adjuvant bicalutamide 150 mg. The median postoperative follow-up time was 27.0 months. The primary endpoint was biochemical recurrence. Of the 209 patients, 59 patients developed biochemical recurrence. There was no difference between the two groups with respect to clinical characteristics, including age, pretreatment prostate-specific antigen, Gleason score, surgical margin status, or pathological stages. The maximum androgen blockage group experienced longer biochemical recurrence-free survival （P = 0.004） compared with the bicalutamide 150 mg group. Side-effects in the two groups were similar and could be moderately tolerated in all patients. In conclusion, immediate, 9-month maximum androgen blockage should be considered as an alternative to bicalutamide 150 mg as adjuvant treatment for high-risk localized prostate cancer patients after radical prostatectomy.

Detection and Local Staging of Prostate Cancer by 68Ga-PSMA-PET/CT, Comparison with mpMRI and Histopathology

Introduction: 68Ga-PSMA-PET/CT has proven its value in prostate cancer with high positive predictive value for lymph node metastasis and superior detection of distant metastasis. There is growing evidence that 68Ga-PSMA- PET/CT has high sensitivity for detection of tumor lesions in the prostate as well. Studies thus far have mainly been performed in patients prior to prostatectomy. Aim of this study is to evaluate diagnostic accuracy in a mixed population of men with increased risk of prostate cancer and evaluate diagnostic possibilities with respect to extra-capsular extension and seminal vesicle invasion. Methods: The population consisted of a retrospectively included sequential cohort of 69 patients with 68Ga-PSMA-PET/CT and mpMRI available. 68Ga-PSMA-PET/CT was re-evaluated by two readers blinded for mpMRI and clinical information. Likelihood of tumour presence, extra-prostatic extension and seminal vesicle invasion was scored on 5-point Likert scale and localized schematically. Results were compared with mpMRI. Available pathological outcome served as gold standard. SUVmax of index lesions was measured and correlated to index tumor Gleason grade. Results: Clinically significant prostate cancer (Gleason ≥ 3 + 4) was detected in 57 (83%) of 69 patients. Diagnostic accuracy was 89% for PET reader 1, 93% for PET reader 2 and 86% for mpMRI. Lesion concordance of 68Ga-PSMA-PET/CT and mpMRI was 97%. SUVmax of the index lesion correlated to Gleason grade. Sensitivity for extracapsular extension in the prostatectomy group was 62% for PET reader 1, 33% for PET reader 2 and 50% for mpMRI. Specificity was 62% for PET reader 1, 100% for PET reader 2 and 69% for mpMRI. Conclusion: Ga68-PSMA-PET shows high accuracy in the detection of tumor lesions in the prostate. Results on evaluating extra-capsular extension and seminal vesicle invasion are comparable to mpMRI. This study adds to the increasing evidence that 68Ga-PSMA-PET/CT is imperative in detection of prostate cancer prior to biopsy.

The Impact of Variation in Bladder Volume on the Doses of Target and Organ-at-Risk in Intensity-Modulated Radiation Therapy for Localized Prostate Cancer

Intensity-modulated radiation therapy (IMRT) has become the mainstay of treatment for localized prostate cancer. In IMRT, minimizing differences between the conditions used during planning CT and daily treatment is important to prevent adverse events in normal tissues. In the present study, we evaluated the impact of variation in bladder volume on the doses to various organs. A total of 35 patients underwent definitive radiotherapy at Saitama Medical Center. A Light Speed RT16 (GE Healthcare) was used for planning and to obtain examination CT images. Such images were acquired after 4 - 6 days of planning CT image acquisition. The IMRT plans were optimized using the planning CT data to satisfy the dose constraints set by our in-house protocols for the PTV and the OARs. The dose distributions were then re-calculated using the same IMRT beams, and checked on examination CT images. It was clear that bladder volume affected the doses to certain organs. We focused on the prostate, bladder, rectum, small bowel, and large bowel. Regression coefficients were calculated for variables that correlated strongly with bladder volume (p < 0.05). We found that variation in bladder volume [cm3] predicted deviations in the bladder V70Gy, V50Gy, and V30Gy [%];the maximum dose to the small bowel [cGy];and the maximum dose to the large bowel [cGy]. The regression coefficients were -0.065, -0.125, -0.180, -10.22, and -9.831, respectively. We evaluated the impacts of such variation on organ doses. These may be helpful when checking a patient’s bladder volume before daily IMRT for localized prostate cancer.

Value of MRI diffusion weighted imaging in localization of prostate cancer with whole-mount step section pathology

Objective To evaluate the value of MRI diffusion weighted imaging in localization of prostate cancer with whole-mount step section pathology. Methods We treated 36 patients using laparoscopic radical prostatectomy from Oct. 2009 to Jun. 2010. Patients who did not have an MRL /DWI examination or a surgical history of pros-

Patient Participation in Communication about Treatment Decision-Making for Localized Prostate Cancer during Consultation Visits

Objectives: To describe the communication behaviors of patients and physicians and patient par-ticipation in communication about treatment decision-making during consultation visits for local-ized prostate cancer (LPCa). Methods: This is a secondary analysis of data from 52 men enrolled in the usual care control group of a randomized trial that focused on decision-making for newly diagnosed men with LPCa. We analyzed the patient-physician communication using the transcribed audio-recordings of real-time treatment consultations and a researcher-developed coding tool, including codes for communication behaviors (information giving, seeking, and clarifying/ verifying) and contents of clinical consultations (health histories, survival/mortality, treatment options, treatment impact, and treatment preferences). After qualitative content analysis, we categorized patient participation in communication about treatment-related clinical content, including “none” (content not discussed);“low” (patient listening only);“moderate” (patient providing information or asking questions);and “high” (patient providing information and asking questions). Results: Physicians mainly provided information during treatment decision consultations and patients frequently were not active participants in communication. The participation of patients with low and moderate cancer risk typically was: 1) “moderate and high” in discussing health histories;2) “low” in discussing survival/mortality;3) “low and moderate” in discussing treatment options;4) “none and low” in discussing treatment impacts;and 5) “low” in discussing treatment preferences. Conclusions: Findings suggest opportunities for increasing patient participation in communication about treatment decision-making for LPCa during clinical consultations.

Long-Term Outcomes and Prognosis of Transrectal High-Intensity Focused Ultrasound Therapy for Patients with Localized Prostate Cancer—Therapy after Recurrence and Predictive Factors

Objectives: To evaluate the outcomes and prognosis of high-intensity focused ultrasound (HIFU) therapy for patients with localized prostate cancer, and identify suitable candidates for this therapy by investigating the predictive factors. Methods: The 224 patients (low 54, intermediate 111 and high-risk patients 59) with T1-2 stage were treated using the Sonablate device and followed for over 12 months after treatment. Recurrence was determined based on histological findings, prostate-specific antigen (PSA) failure and local or distant metastasis. The factors which are predicting variables with potential effects were investigated by Kaplan-Meier and multivariate analysis. Results: A total of 255 treatment sessions (193 with one, 31 with two) were performed. No patients died of prostate cancer, but 15 died of other causes and 14 patients were lost during follow-up. The 7-year recurrence-free survival (RFS) rates in all patients were 75%, and 5-year RFS rates were 98%, 84% and 59% in the low, intermediate and high-risk patients respectively. In the 216 patients who underwent histological examination at 6 months or later after HIFU, 25 (12%) were positive. In 77 patients with recurrence after first-HIFU, the second treatments were hormonal therapy and HIFU. Of the 31 patients who underwent a second HIFU, the 5-year RFS rates were 64%, and 5-year RFS rates were 100%, 74% and 33% in the low, intermediate and high-risk patients. The significant predictor for recurrence was risk-group, T-stage (T1 vs T2), Gleason score (≤3 + 4 and ≥4 + 3), pretreatment PSA (Conclusions: Prognosis of HIFU for Patients with localized prostate cancer was good, and the low and intermediate-risk patients with T1-staging are suitable indications for HIFU. Effective predictors for outcomes were risk-group, T-stage, Gleason score, pretreatment PSA and nadir PSA.

Role of magnetic resonance imaging in the diagnostic work up of clinical localized prostate cancer: A review

Imaging plays an increasingly important role in the work up of prostate cancer(PCa) and magnetic resonance imaging(MRI) is generally accepted as the most accurate and promising imaging modality in the local staging of PCa due to its high spatial resolution and excellent soft tissue contrast. The quality and performance of MRI of the prostate has improved dramatically during the last decade. Mainly, the combination of morphological information and functional information on cell density, tissue perfusion or metabolism as provided in multi-parametric prostate MRI(mp MRI) has led to a substantial increase in lesion detection and characterization. The correlation between functional parameters as provided by MRI and the aggressiveness of PCa as determined by the Gleason Score may help in differentiating clinically signifi cant from indolent PCa non-invasively. Besides these pros, radiologists are confronted with an immense amount of information and standardized acquisition, interpretation and reporting of mp MRI is not yet a reality. Furthermore, prostate MRI availability is still limited to high volume centers in many countries; hence, it is not yet a routine tool in common daily practice. Hence, development of guidelines for standardized acquisition, interpretation andreporting of prostate MRI exams is urgently needed in order to provide useful information for treating clinicians. Preferably, multi-centric clinical studies comparing MRI fi ndings to step-section histological specimens are mandatory during the coming years. Furthermore, simplification of the acquisition must be achieved in order to make this imaging modality applicable for daily use in common uro-radiological practice.

Splenunculi mimicking metastases in a patient with locally advanced prostate cancer

A 61-year-old man with locally advanced prostate cancer was found to have multiple solid intra-abdominal solid lesions during staging investigations.While some were in the pelvis,they were not located in the common landing sites for prostate cancer metastases,and his prostate specific antigen was not significantly elevated to suggest a high burden of metastatic disease.He reported a history of a blunt abdominal trauma due to a motor vehicle accident more than forty years ago which had been conservatively managed.His staging imaging revealed a lack of a discrete spleen in his left upper abdomen and this raised the suspicion that these solid lesions may represent ectopic splenic tissue.Imaging with nuclear medicine scintigraphy confirmed the lesions in his upper abdomen and pelvis to be splenunculi.He proceeded with a combination of androgen deprivation therapy and external beam radiotherapy for locally advanced,non-metastatic prostate cancer.Although it has been described in patients with low risk prostate cancer,this is the first case report of splenunculi mimicking metastases in a patient with locally advanced prostate cancer.

Combined cryotherapy and external beam radiation therapy for the treatment of intermediate-risk localized prostate cancer: A case series

Introduction: Routine PSA screening for prostate cancer (PCa) has increased the detection of intermediate-risk, localized disease. Conventional treatments for localized PCa include surgery, brachytherapy, cryotherapy or external beam radiotherapy (EBRT). However, for intermediate risk patients, rates of recurrence are moderately high and a multi-modal treatment approach for these patients may be necessary. We treated patients with a combination of cryotherapy and low dose EBRT to assess the safety and feasibility of this combinatory approach as well as to evaluate early oncological outcomes. Case Presentation: Men with intermediate risk (PSA = 10-20 ng/ml and/or Gleason = 7 and/or clinical T2b) localized PCa were prospectively enrolled in this study. Patients underwent cryotherapy and then 39 Gy EBRT 4-6 weeks after surgery. After completing EBRT, the men were followed every 3 months for 2 years. Adverse events, PSA, urinary and erectile function were assessed during each follow-up. Three patients completed the study. Preoperative PSA ranged from 3.5 to 7.9 ng/ml. There were no intraoperative complications and the treatment was well tolerated. Following cryotherapy and EBRT, all patients were pad-free within 6 months and remained continent for the duration of the study. Bother index remained stable throughout the study for all patients. No urethral strictures or rectal toxicities were observed. PSA remained undetectable for all patients. Conclusions: In this prospective study, cryotherapy combined with low dose EBRT was a safe approach for the treatment of intermediate-risk, localized PCa. Early oncological outcomes appeared to be favorable with all patients having undetectable PSA during the 2-year follow-up period. Further studies are warranted to confirm these preliminary results.

Relationship between D90 and D100 with Biochemical and Local Failure in Low-risk Prostate Cancer Treated with Low-rate Brachytherapy(LDR)

Low dose rate brachytherapy(LDR)is an accepted,effective treatment with few local side effects,used as monotherapy in patients with low-risk prostate cancer(PC).The aim of this paper is to analyse 245 patients treated with LDR in the Radiation Oncology Department of the Hospital Gómez Ulla,from 2004 to 2016,evaluating the relationship of dosimetric parameters with biochemical and local recurrence as well as genitourinary and gastrointestinal toxicity derived from the technique.The results obtained show a clear relationship between the dose used and biochemical and local failure.

Neoadjuvant hormone therapy for patients with high-risk prostate cancer:a systematic review and meta-analysis

This study aimed to identify the pathological outcomes and survival benefits of neoadjuvant hormone therapy(NHT)combined with radical prostatectomy(RP)and radiotherapy(RT)administered to patients with high-risk prostate cancer(HRPCa).We searched PubMed,Embase,and the Cochrane Library for studies comparing NHT plus RP or RT with RP or RT alone,administered to patients with HRPCa.We used a random-effects model to compute risk estimates with 95%confidence intervals(CIs)and quantified heterogeneity using the I2 statistic.Subgroup and sensitivity analyses were performed to identify potential sources of heterogeneity.We selected 16 studies.NHT before RP significantly decreased lymph node involvement(risk ratio[RR]=0.69,95%CI:0.56–0.87)and increased the rates of pathological downstaging(RR=2.62,95%CI:1.22–5.61)and organ-confinement(RR=2.24,95%CI:1.54–3.25),but did not improve overall survival and biochemical progression-free survival(bPFS).The administration of NHT before RT to patients with HRPCa was associated with significant benefits for cancer-specific survival(hazard ratio[HR]=0.51,95%CI:0.39–0.68),disease-free survival(HR=0.51,95%CI:0.44–0.60),and bPFS(HR=0.54,95%CI:0.46–0.64).Short-term NHT combined with RT administered to patients with HRPCa conferred significant improvements.Although the advantage of local control was observed when NHT was administered before RP,there was no significant survival benefit associated with HRPCa.Therefore,short-term NHT combined with RT is recommended for implementation in standard clinical practice but not for patients who undergo RP.

Cytoreductive radical prostatectomy after chemohormonal therapy in patients with primary metastatic prostate cancer

Objective:Cytoreductive radical prostatectomy(cRP)has been proposed as local treatment option in metastatic hormone-sensitive prostate cancer(mHSPC)to prevent local complications and potentially improve oncological outcomes.In this study,we examined the feasibility of a multimodal concept with primary chemohormonal therapy followed by cRP and analyzed prostate size reduction under systemic treatment,postoperative complication rates,as well as early postoperative continence.Methods:In this retrospective study,38 patients with mHSPC underwent cRP after primary chemohormonal therapy(3-monthly luteinising hormone-releasing hormone-analogue+six cycles 3-weekly docetaxel 75 mg/m2)at two centers between September 2015 and December 2018.Results:Overall,10(26%)patients had high volume and 28(74%)patients had low volume disease at diagnosis,according to CHAARTED definition.Median prostate-specific antigen(PSA)decreased from 65 ng/mL(interquartile range[IQR]35.0-124.5 ng/mL)pre-chemotherapy to 1 ng/mL(IQR 0.3-1.7 ng/mL)post-chemotherapy.Prostate gland volume was significantly reduced by a median of 50%(IQR 29%-56%)under chemohormonal therapy(p=0.003).Postoperative histopathology showed seminal vesicle invasion in 33(87%)patients and negative surgical margins in 17(45%)patients.Severe complications(Grade 3 according to Clavien-Dindo)were observed in 4(11%)patients within 30 days.Continence was reached in 87%of patients after 1 month and in 92%of patients after 6 months.Median time to castration-resistance from begin of chemohormonal therapy was 41.1 months and from cRP was 35.9 months.Postoperative PSA-nadir≤1 ng/mL versus>1 ng/mL was a significant predictor of time to castration-resistance after cRP(median not reached versus 5.3 months;p<0.0001).Conclusion:We observed a reduction of prostate volume under chemohormonal therapy going along with a low postoperative complication and high early continence rate.However,the oncologic benefit from cRP is still under evaluation.

A prospective cohort of men with localized prostate cancer on active surveillance protocol in Hong Kong,China:what did we learn?

This study aimed to report the outcomes of active surveillance(AS)in the management of low-risk prostate cancer(PCa).It recruited87 men who were prospectively followed up according to the Prostate Cancer Research International Active Surveillance(PRIAS)protocol with local adaptation at SH Ho Urology Centre,Prince of Wales Hospital,Hong Kong,China.We investigated the predictorsof disease progression and found that baseline prostate-specific antigen density(PSAD)and the presence of the highest ProstateImaging-Reporting and Data System(PI-RADS)score 5 lesion on magnetic resonance imaging(MRI)are significantly correlatedwith disease progression.Moreover,men with PSAD>0.2 ng ml^(−2)or PI-RADS 4 or 5 lesions had significantly worse upgradingfree survival compared to those with PSAD≤0.2 ng ml−2 and PI-RADS 2 or 3 lesions.The study concludes that AS is a safe andeffective management strategy for selected patients to defer radical treatment and that most disease progression can be detectedafter the first repeated biopsy.The combination of PSAD>0.2 ng ml^(−2)and PI-RADS 4 or 5 lesions may serve as a useful predictorof early disease progression and provide a guide to optimize follow-up protocols for men in different risk groups.

Consolidation chemotherapy with capecitabine after neoadjuvant chemoradiotherapy in high-risk patients with locally advanced rectal cancer:Propensity score study

BACKGROUND The effects of consolidation chemotherapy(CC) in neoadjuvant therapy in locally advanced rectal cancer(LARC) have been explored. However, the optimal neoadjuvant chemoradiotherapy(NCRT) and surgery interval, regimen, and cycles of chemotherapy remains unclear.AIM To evaluate the effects of one to two cycles of CC with capecitabine on high-risk patients with LARC without extending NCRT and surgery interval.METHODS We retrospectively evaluated high-risk patients with LARC, who were defined as having at least one of the following factors by magnetic resonance imaging: depth of invasion beyond the muscularis propria of more than 5 mm(c T3c-c T3d), T4, meso-rectal fascia or extramural vascular invasion positive, and treatment date between January 2015 and July 2019 in our center. Patients were divided into the CC and non-CC group according to whether they received CC(capecitabine 1000 mg/m^(2) twice daily from days 1 to 14 every 21 d) after NCRT. Propensity score matching(PSM) and inverse probability of treatment weight(IPTW) were used to balance the differences between the two groups. The main outcome was the complete response(CR) rate.RESULTS A total of 265 patients were enrolled: 136 patients in the CC group and 129 patients in the non-CC group. The median interval was 70 d(range, 37-168). The CR rate was 24.3% and 16.3%(P = 0.107) in the CC and non-CC groups’ original samples, respectively. After PSM and IPTW, the CR rate in the CC group was higher than that in non-CC group(27.6% vs 16.2%, P = 0.045;25.9% vs 16.3%, P = 0.045). The median follow-up was 39.8 mo(range, 2.9-74.8), and there were no differences in 3-year non-regrowth disease-free survival nor overall survival in the original samples(73.2% vs 71.9%, P = 0.913;92.3% vs 86.7%, P = 0.294), PSM(73.2% vs 73.5%, P = 0.865;92.5% vs 89.3%, P = 0.612), and IPTW(73.8% vs 72.1%, P = 0.913;92.4% vs 87.4%, P = 0.294). There was also no difference in grade 2 or higher acute toxicity during neoadjuvant therapy in the two groups(49.3% vs 53.5%, P = 0.492).CONCLUSION One to two cycles of CC with capecitabine after NCRT was safe and increased the CR rate in highrisk LARC but failed to improve the long-term outcomes.

Malignant field expression signatures in biopsy samples at diagnosis predict the likelihood of lethal disease in patients with localized prostate cancer

Aim:Overtreatment of early-stage low-risk prostate cancer patients represents a significant problem in disease management and has significant socio-economic implications.Changes in prostate cancer screening and treatment practices in the United States have been associated with the recent decline in overall incidence and concomitant significant increase of the annual incidence of metastatic prostate cancer has been documented.Therefore,development of genetic and molecular markers of clinically significant disease in patients diagnosed with low grade localized prostate cancer would have a major impact in disease management.Methods:Identification of gene expression signatures(GES)associated with lethal prostate cancer has been performed using microarray analyses of biopsy specimens obtained at the time of diagnosis from 281 patients with Gleason 6(G6)and G7 tumors in a Swedish watchful waiting cohort with up to 30 years follow-up.The performance of GES has been validated in independent cohort of 568 prostate cancer patients of the Cancer Genome Anatomy Project Prostate Cancer database.Results:GES c omprising 98 genes identified 89%and 100%of all death events 4 years after diagnosis in G7 and G6 patients,respectively.At 6 years follow-up,83%and 100%of all deaths events were captured in G7 and G6 patients,respectively.Remarkably,the 98-gene signature appears to perform successfully in patients stratification with as little as 2%of cancer cells in a specimen,strongly indicating that it captures a malignant field effect in human prostates harboring cancer cells of different degrees of aggressiveness.In G6 and G7 tumors from prostate cancer patients of age 65 or younger,GES identified 86%of all death events during the entire follow-up period.In G6 and G7 tumors from prostate cancer patients of age 70 or younger,GES identified 90%of all death events 6 years after diagnosis.Conclusion:Classification performance of the reported in this study 98-genes GES of lethal prostate cancer appeared suitable to meet design and feasibility requirements of a prospective 4 to 6 years clinical trial,which is essential for regulatory approval of diagnostic and prognostic tests in clinical setting.Prospectively validated GES of lethal PC in biopsy specimens of G6 and G7 tumors will help physicians to identify,at the time of diagnosis,patients who should be considered for exclusion from active surveillance programs and who would most likely benefit from immediate curative interventions.

Performance of^(18)F‑DCFPyL PET/CT in Primary Prostate Cancer Diagnosis,Gleason Grading and D'Amico Classifcation:A Radiomics‑Based Study

This study aimed to investigate the performance of^(18)F-DCFPyL positron emission tomography/computerized tomography(PET/CT)models for predicting benign-vs-malignancy,high pathological grade(Gleason score>7),and clinical D'Amico classifcation with machine learning.The study included 138 patients with treatment-naïve prostate cancer presenting positive^(18)F-DCFPyL scans.The primary lesions were delineated on PET images,followed by the extraction of tumor-to-backgroundbased general and higher-order textural features by applying fve diferent binning approaches.Three layer-machine learning approaches were used to identify relevant in vivo features and patient characteristics and their relative weights for predicting high-risk malignant disease.The weighted features were integrated and implemented to establish individual predictive models for malignancy(Mm),high path-risk lesions(by Gleason score)(Mgs),and high clinical risk disease(by amico)(Mamico).The established models were validated in a Monte Carlo cross-validation scheme.In patients with all primary prostate cancer,the highest areas under the curve for our models were calculated.The performance of established models as revealed by the Monte Carlo cross-validation presenting as the area under the receiver operator characteristic curve(AUC):0.97 for Mm,AUC:0.73 for Mgs,AUC:0.82 for Mamico.Our study demonstrated the clinical potential of^(18)F-DCFPyL PET/CT radiomics in distinguishing malignant from benign prostate tumors,and high-risk tumors,without biopsy sampling.And in vivo^(18)F-DCFPyL PET/CT can be considered a noninvasive tool for virtual biopsy for personalized treatment management.