Publications by authors named "Derya Tilki"

387 Publications

Immuno-oncology therapy in metastatic bladder cancer: a systematic review and network meta-analysis.

Crit Rev Oncol Hematol 2021 Nov 22:103534. Epub 2021 Nov 22.

Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Québec, Canada.

Context: Three first line and three second-line clinical trials tested the effect of immunotherapy (IO) relative to standard chemotherapy (CT) on overall survival. However, network meta-analysis-based comparisons have not yet been presented. We addressed this void.

Objective: To provide comparisons of overall survival (OS), progression-free survival (PFS), complete response (CR), partial response (PR), stable disease (SD), objective response rates (ORR), disease control rates (DCR) and adverse events (AEs) associated with 1 and 2 line IO-based regimens.

Materials And Methods: PubMed was searched for phase III randomized controlled trials from 2016 to 2021, including conference abstracts. We identified three first line [IMvigor130 (atezolizumab + CT vs atezolizumab vs CT), DANUBE (durvalumab vs durvalumab + tremelimumab vs CT), and KEYNOTE-361 (pembrolizumab + CT vs pembrolizumab vs CT)] and two second line [KEYNOTE-045 (pembrolizumab vs CT) and IMvigor211 (atezolizumab vs CT)] RCTs.

Results: Overall, 3,255 and 1,452 patients were respectively included in the first- and second-line settings. In 1 line setting, compared with CT, no IO-based regimen exhibited survival benefit. However, all exclusive IO regimens resulted in lower rates of grade 3+ AEs. In 2 line setting, compared with CT, only pembrolizumab improved OS benefit. Conversely, atezolizumab only showed OS benefit in exploratory analyses. Compared to second-line CT, no experimental regimen (atezolizumab or pembrolizumab) exhibited statistically significant ORR benefit. Both pembrolizumab and atezolizumab resulted in lower rates of grade 3+ AEs compared to 2 line CT.

Conclusions: In metastatic UC, IO-based regimens do not hold a survival benefit relative to CT in 1 line setting. However, pembrolizumab holds a survival benefit in 2 line compared to CT. Several IO-based clinical trials are ongoing and will provide more and possibly better treatment alternatives for locally advanced and metastatic UC.
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http://dx.doi.org/10.1016/j.critrevonc.2021.103534DOI Listing
November 2021

Features and management of men with pN1 cM0 prostate cancer after radical prostatectomy and lymphadenectomy: a systematic review of population-based evidence.

Curr Opin Urol 2022 Jan;32(1):69-84

Department of Urology, Institut Mutualiste Montsouris, Paris, France.

Purpose Of Review: To investigate the features and optimal management of pN+ cM0 prostate cancer (PCa) according to registry-based studies.

Recent Findings: Up to 15% of PCa patients harbor lymph node invasion (pN+) at radical prostatectomy plus lymph node dissection. Nonetheless, the optimal management strategy in this setting is not well characterized.

Summary: We performed a systematic review including n = 13 studies. Management strategies comprised 13 536 men undergoing observation, 11 149 adjuvant androgen deprivation therapy (aADT), 7,075 adjuvant radiotherapy (aRT) +aADT and 705 aRT. Baseline features showed aggressive PCa in the majority of men. At a median follow-up ranging 48-134months, Cancer-related death was 5% and overall-mortality 16.6%. aADT and aRT alone had no cancer-specific survival or overall survival advantages over observation only and over not performing aRT, respectively. aADT plus aRT yielded a survival benefit compared to observation and aADT, which in one study, were limited to certain intermediate-risk categories. Age, Gleason, Charlson score, positive surgical margins, pathological stage, and positive nodes number, but not prostate specific antigen, were most relevant prognostic factors. Our work further confirmed pN+ PCa is a multifaceted disease and will help future research in defining its optimal management based on different risk categories to maximize survival and patient's quality of life.
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http://dx.doi.org/10.1097/MOU.0000000000000946DOI Listing
January 2022

Concordance of biopsy and pathologic ISUP grading in salvage radical prostatectomy patients for recurrent prostate cancer.

Prostate 2021 Nov 22. Epub 2021 Nov 22.

Martini-Klinik Prostate Cancer Center, University Hospital Hamburg Eppendorf, Hamburg, Germany.

Purpose: To investigate the concordance of biopsy and pathologic International Society of Urological Pathology (ISUP) grading in salvage radical prostatectomy (SRP) patients for recurrent prostate cancer.

Methods: Within a high-volume center database, we identified patients who underwent SRP for recurrent prostate cancer (PCa) between 2004 and 2020. Upgrading, downgrading, concordance, and any discordance between posttreatment biopsy ISUP and ISUP at SRP were tested. Logistic regression models were used to predict ISUP upgrading and ISUP discordance. Models were adjusted for prostatic specific antigen before SRP, age at surgery, initial prostatic specific antigen (PSA), type of primary treatment, time from primary PCa diagnosis to SRP, number of positive cores at biopsy, and original Gleason score.

Results: Overall, 184 patients with available biopsy and pathologic ISUP grading were identified. Of those, 17.4% (n = 32), 40.8% (n = 75), 19.6% (n = 36), and 22.2% (n = 41) harbored biopsy ISUP 1, ISUP 2, ISUP 3, and ISUP 4-5 grading, respectively. Pathologic ISUP 1, ISUP 2, ISUP 3, and ISUP 4-5 grading was recorded in 6.0% (n = 11), 40.8% (n = 75), 32.1% (n = 59), and 21.2% (n = 39), respectively. Median PSA before SRP was 5.5 ng/ml (interquartile range [IQR]: 3.1-8.1 ng/ml), median age at SRP was 65.1 years (IQR:60.7-69.4 years) and median time from original PCa diagnosis to SRP was 47 months (IQR: 27.3-85.2 months). Concordance of biopsy and pathologic ISUP was identified in 45.1% (n = 83). Conversely, any ISUP discordance, upgrading and downgrading of at least one ISUP group was identified in 54.9% (n = 101), 35.3% (n = 65), and 19.6% (n = 36). In logistic models, none of the preoperative characteristics was associated with upgrading or ISUP discordance (all p > 0.1).

Conclusion: Discordance between biopsy and pathologic ISUP grading is common at SRP. However, in 45% of SRP cases biopsy ISUP is capable to predict pathologic ISUP. Further studies are necessary to identify characteristics for ISUP upgrading at SRP.
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http://dx.doi.org/10.1002/pros.24268DOI Listing
November 2021

Possible Role of Circulating Tumour Cells for Prediction of Salvage Lymph Node Dissection Outcome in Patients with Early Prostate Cancer Recurrence.

Eur Urol Open Sci 2021 Dec 2;34:55-58. Epub 2021 Nov 2.

Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany.

Promising oncological results have been reported for salvage lymph node dissection (SLND) with prostate-specific membrane antigen-radioguided surgery (PSMA-RGS) in patients with prostate cancer (PCa) recurrence. We performed a proof-of-principle study assessing circulating tumour cells (CTCs) as a prognostic marker in patients undergoing SLND. Twenty consecutive patients with recurrent PCa treated with PSMA-RGS during April-July 2019 for PSMA-positive LNs were evaluated. Preoperative CTC counts were assessed using the US Food and Drug Administration-approved CellSearch system. Biochemical recurrence (BCR)-free survival (BFS) and therapy-free survival (TFS) were evaluated using the Kaplan-Meier method. Overall, three patients (15%) were CTC-positive. Postoperatively, CTC-positive patients had more pathologically positive LNs (median 8 vs 2) without a difference in overall LN count. During median follow-up of 10.1 mo, 14 patients experienced BCR and five received further therapy. In Kaplan-Meier analyses, median BFS was 1.4 versus 4.3 mo and median TFS was 10.3 mo versus not reached for CTC-positive versus CTC-negative patients. The main limitations are the small number of patients, the retrospective design, and short follow-up. Our pilot study suggests that CTC-positive patients seem to have worse pathological and short-term oncological outcomes. Therefore, further validation of this biomarker for treatment decision-making before local salvage therapy could be of value.

Patient Summary: We looked at outcomes for lymph node dissection in patients with recurrence of prostate cancer. We found that outcomes appear to be worse when circulating tumour cells (CTCs) can be measured in the blood preoperatively. We conclude that detection of CTCs indicates spread of tumour cells via the blood, which may limit the benefit of lymph node dissection. Thus, CTCs should be investigated in further studies as a potential marker to help in selecting patients who could benefit from lymph node dissection if their prostate cancer recurs.
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http://dx.doi.org/10.1016/j.euros.2021.09.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8579141PMC
December 2021

Has the COVID-19 outbreak changed the way we are treating prostate cancer? An EAU - YAU Prostate Cancer Working Group multi-institutional study.

Cent European J Urol 2021 18;74(3):362-365. Epub 2021 Sep 18.

Division of Oncology/Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy.

Introduction: The COVID-19 outbreak has become the dominant issue throughout the world whilst the governments, nations and health services are trying to deal with its impact. The aim of our study is to assess the impact of COVID-19 on patients treated with radical prostatectomy (RP) for prostate cancer (PCa) at European referral centers in terms of surgical volume (SV), waiting list meant as time from biopsy to surgery (WL) and risk of adverse pathologic findings at RP due to the selection of men with more adverse disease characteristics at final pathology.

Material And Methods: Consecutive patients with a diagnosis of histologically proven PCa treated with RP between March 2020 (WHO declaration of pandemic) and December 2020 were identified. Patients with metastatic disease not eligible to local treatment and recurrent prostate cancer after RP or RT were excluded. Patients treated at the same institutions between March 2019 and December 2019 were considered as the control group. Multivariable logistic regression analysis tested the impact of the COVID-19 outbreak on the risk of adverse pathologic findings at RP after adjusting for confounders. The percentage change of SV and WL was assessed comparing the months of pandemic with the equivalent timespan of the previous year.

Results: A total of 2,574 patients treated with RP (927 cases and 1647 controls) were identified in 8 European tertiary referral centers. At multivariable analysis patients who were treated during the pandemic had higher risk of extra prostatic disease (OR:1.35, p = 0.038) and lymph node invasion (LNI) (OR:1.72, p = 0.048). An average 23% reduction of the SV with the equivalent timespan of the previous year allowed an illusory reduction of the WL after the peak gained during the first wave of COVID-19.

Conclusions: Our results showed that the COVID-19 outbreak resulted in a delay in the administration of curative-intent therapies in patients with localized PCa. This, in turn, resulted in a stage migration phenomenon with a potential impact on oncologic control.
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http://dx.doi.org/10.5173/ceju.2021.0211DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8552935PMC
September 2021

Management and treatment options for patients with de novo and recurrent hormone-sensitive oligometastatic prostate cancer.

Prostate Int 2021 Sep 18;9(3):113-118. Epub 2021 Jan 18.

Department of Urology, University Hospital Frankfurt, Frankfurt, Germany.

Probably, patients with de novo (synchronous) and recurrent (metachronous) oligometastatic hormone-sensitive prostate cancer have different oncologic outcomes. Thus, we are challenged with different scenarios in clinical practice, where different treatment options may apply. In the last years, several prospective studies have focused on the treatment of patients with de novo oligometastatic hormone-sensitive prostate cancer. Not only the addition of systemic therapeutic treatments, such as chemotherapy with docetaxel, abiraterone, enzalutamide, and apalutamide, next to androgen deprivation therapy, demonstrated to improve outcomes in these patients but also local therapy of the primary has been demonstrated to improve outcomes of low-volume metastatic disease. Next to radiotherapy, also radical prostatectomy has been reported as a feasible and safe treatment option. Additional metastasis-directed therapy in de novo metastatic disease is currently examined by four trials. In the recurrent metastatic setting, less data are available, and it remains uncertain if patients can be treated in the same way as synchronous oligometastatic disease. Metastasis-directed therapy has demonstrated to prolong outcomes, while data on survival are still missing.
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http://dx.doi.org/10.1016/j.prnil.2020.12.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8498729PMC
September 2021

The Effect of 10 Most Common Nonurological Primary Cancers on Survival in Men With Secondary Prostate Cancer.

Front Oncol 2021 6;11:754996. Epub 2021 Oct 6.

Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, QC, Canada.

Background: This study aims to test the effect of the 10 most common nonurological primary cancers (skin, rectal, colon, lymphoma, leukemia, pancreas, stomach, esophagus, liver, lung) on overall mortality (OM) after secondary prostate cancer (PCa).

Material And Methods: Within the Surveillance, Epidemiology, and End Results (SEER) database, patients with 10 most common primary cancers and concomitant secondary PCa (diagnosed 2004-2016) were identified and were matched in 1:4 fashion (age, year at diagnosis, race/ethnicity, treatment type, TNM stage) with primary PCa controls. OM was compared between secondary and primary PCa patients and was stratified according to primary cancer type, as well as according to time interval between primary cancer secondary PCa diagnoses.

Results: We identified 24,848 secondary PCa patients (skin,  = 3,871; rectal,  = 798; colon,  = 3,665; lymphoma,  = 2,583; leukemia,  = 1,102; pancreatic,  = 118; stomach,  = 361; esophagus,  = 219; liver,  = 160; lung,  = 1,328) 531,732 primary PCa patients. Secondary PCa characteristics were less favorable than those of primary PCa patients (PSA and grade), and smaller proportions of secondary PCa patients received active treatment. After 1:4 matching, all secondary PCa exhibited worse OM than primary PCa patients. Finally, subgroup analyses showed that the survival disadvantage of secondary PCa patients decreased with longer time interval since primary cancer diagnosis and subsequent secondary PCa.

Conclusion: Patients with secondary PCa are diagnosed with less favorable PSA and grade. Even after matching for PCa characteristics, secondary PCa patients still exhibit worse survival. However, the survival disadvantage is attenuated, when secondary PCa diagnosis is made after longer time interval, since primary cancer diagnosis.
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http://dx.doi.org/10.3389/fonc.2021.754996DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8526938PMC
October 2021

Survival benefit of chemotherapy in a contemporary cohort of metastatic urachal carcinoma.

Urol Oncol 2021 Oct 19. Epub 2021 Oct 19.

Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Québec, Canada.

Background: We relied on the most contemporary Surveillance, Epidemiology, and End Results (SEER) database and tested the hypothesis that chemotherapy may improve survival in metastatic urachal carcinoma (m-UraC).

Material And Methods: Within the SEER database (2004-2016), we identified m-UraC patients aged ≥ 18 years. Propensity score matching (PSM: cystectomy status, age and sex), Kaplan-Meier plots, cumulative incidence plots, Cox regression models and competing risks regression (CRR) models addressed overall mortality (OM) and cancer-specific mortality (CSM).

Results: Overall, 274 m-UraC patients were identified with a median age of 70 years. Most were male (66%) and Caucasian (72%). Overall, 32% received chemotherapy. Chemotherapy-exposed patients were younger (62 vs. 73 years, p<0.001) and more frequently underwent cystectomy (19 vs. 8%, P = 0.014). In 274 m-UraC patients, median OM and CSM were 6 (4 -10) months and 8 (6 -14) months, respectively. After 1:1 PSM, chemotherapy-exposed patients exhibited lower OM (median 16 vs. 3 months; multivariable HR 0.38, P <0.001) and lower CSM (median 17 vs. 4 months; multivariable CRR HR 0.52, P = 0.001). The association between chemotherapy and better survival was even stronger in younger (≤70 years) patients (OM HR: 0.23, P <0.001; CSM CRR HR: 0.42, P = 0.001), but not in older (≥71 years) patients (OM HR: 0.61, P = 0.2; CSM CRR HR: 1.02, P = 1), after PSM and multivariable adjustments.

Conclusion: Overall, we validated the very aggressive nature of UraC, when distant metastases are present, and observed that m-UraC patients exposed to chemotherapy exhibited lower OM and CSM.
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http://dx.doi.org/10.1016/j.urolonc.2021.09.008DOI Listing
October 2021

Survival rates with external beam radiation therapy in newly diagnosed elderly metastatic prostate cancer patients.

Prostate 2021 Oct 11. Epub 2021 Oct 11.

Division of Urology, Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Québec, Canada.

Background: The survival benefit of primary external beam radiation therapy (EBRT) has never been formally tested in elderly men who were newly diagnosed with metastatic prostate cancer (mPCa). We hypothesized that elderly patients may not benefit of EBRT to the extent as younger newly diagnosed mPCa patients, due to shorter life expectancy.

Methods: We relied on Surveillance, Epidemiology and End Results (2004-2016) to identify elderly newly diagnosed mPCa patients, aged >75 years. Kaplan-Meier, univariable and multivariable Cox regression models, as well as Competing Risks Regression models tested the effect of EBRT versus no EBRT on overall mortality (OM) and cancer-specific mortality (CSM).

Results: Of 6556 patients, 1105 received EBRT (16.9%). M1b stage was predominant in both EBRT (n = 823; 74.5%) and no EBRT (n = 3908; 71.7%, p = 0.06) groups, followed by M1c (n = 211; 19.1% vs. n = 1042; 19.1%, p = 1) and M1a (n = 29; 2.6% vs. n = 268; 4.9%, p < 0.01). Median overall survival (OS) was 23 months for EBRT and 23 months for no EBRT (hazard ratio [HR]: 0.97, p = 0.6). Similarly, median cancer-specific survival (CSS) was 29 months for EBRT versus 30 months for no EBRT (HR: 1.04, p = 0.4). After additional multivariable adjustment, EBRT was not associated with lower OM or lower CSM in the entire cohort, as well as after stratification for M1b and M1c substages.

Conclusions: In elderly men who were newly diagnosed with mPCa, EBRT does not affect OS or CSS. In consequence, our findings question the added value of local EBRT in elderly newly diagnosed mPCa patients.
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http://dx.doi.org/10.1002/pros.24249DOI Listing
October 2021

External beam radiotherapy and radical prostatectomy are associated with better survival in Asian prostate cancer patients.

Int J Urol 2021 Sep 22. Epub 2021 Sep 22.

Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Quebec, Canada.

Objectives: To test the effect of race/ethnicity on cancer-specific mortality after radical prostatectomy or external beam radiotherapy in localized prostate cancer patients.

Methods: In the Surveillance, Epidemiology and End Results database 2004-2016, we identified intermediate-risk and high-risk white (n = 151 632), Asian (n = 11 189), Hispanic/Latino (n = 20 077) and African American (n = 32 550) localized prostate cancer patients, treated with external beam radiotherapy or radical prostatectomy. Race/ethnicity-stratified cancer-specific mortality analyses relied on competing risks regression, after propensity score matching for patient and cancer characteristics.

Results: Compared with white patients, Asian intermediate- and high-risk external beam radiotherapy patients showed lower cancer-specific mortality (hazard ratio 0.58 and 0.70, respectively, both P ≤ 0.02). Additionally, Asian high-risk radical prostatectomy patients also showed lower cancer-specific mortality than white patients (hazard ratio 0.72, P = 0.04), but not Asian intermediate-risk radical prostatectomy patients (P = 0.08). Conversely, compared with white patients, African American intermediate-risk radical prostatectomy patients showed higher cancer-specific mortality (hazard ratio 1.36, P = 0.01), but not African American high-risk radical prostatectomy or intermediate- and high-risk external beam radiotherapy patients (all P ≥ 0.2). Finally, compared with white people, no cancer-specific mortality differences were recorded for Hispanic/Latino patients after external beam radiotherapy or radical prostatectomy, in both risk levels (P ≥ 0.2).

Conclusions: Relative to white patients, an important cancer-specific mortality advantage applies to intermediate-risk and high-risk Asian prostate cancer patients treated with external beam radiotherapy, and to high-risk Asian patients treated with radical prostatectomy. These observations should be considered in pretreatment risk stratification and decision-making.
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http://dx.doi.org/10.1111/iju.14701DOI Listing
September 2021

Improvement in overall and cancer-specific survival in contemporary, metastatic prostate cancer chemotherapy exposed patients.

Prostate 2021 Dec 15;81(16):1374-1381. Epub 2021 Sep 15.

Division of Urology, Cancer Prognostics and Health Outcomes Unit, University of Montréal Health Center, Montréal, Québec, Canada.

Introduction: Over the last decade, multiple clinical trials demonstrated improved survival after chemotherapy for metastatic prostate cancer (mPCa). However, real-world data validating this effect within large-scale epidemiological data sets are scarce. We addressed this void.

Materials And Methods: Men with de novo mPCa were identified and systemic chemotherapy status was ascertained within the Surveillance, Epidemiology, and End Results database (2004-2016). Patients were divided between historical (2004-2013) versus contemporary (2014-2016). Chemotherapy rates were plotted over time. Kaplan-Meier plots and Cox regression models with additional multivariable adjustments addressed overall and cancer-specific mortality. All tests were repeated in propensity-matched analyses.

Results: Overall, 19,913 patients had de novo mPCa between 2004 and 2016. Of those, 1838 patients received chemotherapy. Of 1838 chemotherapy-exposed patients, 903 were historical, whereas 905 were contemporary. Chemotherapy rates increased from 5% to 25% over time. Median overall survival was not reached in contemporary patients versus was 24 months in historical patients (hazard ratio [HR]: 0.55, p < 0.001). After propensity score matching and additional multivariable adjustment (age, prostate-specific antigen, GGG, cT-stage, cN-stage, cM-stage, and local treatment) a HR of 0.55 (p < 0.001) was recorded. Analyses were repeated for cancer-specific mortality after adjustment for other cause mortality in competing risks regression models and recorded virtually the same findings before and after propensity score matching (HR: 0.55, p < 0.001).

Conclusions: In mPCa patients, chemotherapy rates increased over time. A concomitant increase in survival was also recorded.
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http://dx.doi.org/10.1002/pros.24235DOI Listing
December 2021

Increased risk of postoperative in-hospital complications after radical prostatectomy in patients with prior organ transplant.

Prostate 2021 Dec 13;81(16):1294-1302. Epub 2021 Sep 13.

Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Canada.

Background: To analyze postoperative, in-hospital, complication rates in patients with organ transplantation before radical prostatectomy (RP).

Methods: From National Inpatient Sample (NIS) database (2000-2015) prostate cancer patients treated with RP were abstracted and stratified according to prior organ transplant versus nontransplant. Multivariable logistic regression models predicted in-hospital complications.

Results: Of all eligible 202,419 RP patients, 216 (0.1%) underwent RP after prior organ transplantation. Transplant RP patients exhibited higher proportions of Charlson comorbidity index ≥2 (13.0% vs. 3.0%), obesity (9.3% vs. 5.6%, both p < 0.05), versus to nontransplant RP. Of transplant RP patients, 96 underwent kidney (44.4%), 44 heart (20.4%), 40 liver (18.5%), 30 (13.9%) bone marrow, <11 lung (<5%), and <11 pancreatic (<5%) transplantation before RP. Within transplant RP patients, rates of lymph node dissection ranged from 37.5% (kidney transplant) to 60.0% (bone marrow transplant, p < 0.01) versus 51% in nontransplant patients. Regarding in-hospital complications, transplant patients more frequently exhibited, diabetic (31.5% vs. 11.6%, p < 0.001), major (7.9% vs. 2.9%) cardiac complications (3.2% vs. 1.2%, p = 0.01), and acute kidney failure (5.1% vs. 0.9%, p < 0.001), versus nontransplant RP. In multivariable logistic regression models, transplant RP patients were at higher risk of acute kidney failure (odds ratio [OR]: 4.83), diabetic (OR: 2.81), major (OR: 2.39), intraoperative (OR: 2.38), cardiac (OR: 2.16), transfusion (OR: 1.37), and overall complications (1.36, all p < 0.001). No in-hospital mortalities were recorded in transplant patients after RP.

Conclusions: Of all transplants before RP, kidney ranks first. RP patients with prior transplantation have an increased risk of in-hospital complications. The highest risk, relative to nontransplant RP patients appears to acute kidney failure.
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http://dx.doi.org/10.1002/pros.24224DOI Listing
December 2021

Temporal trends, tumor characteristics and stage-specific survival in penile non-squamous cell carcinoma vs. squamous cell carcinoma.

Cancer Causes Control 2021 Sep 2. Epub 2021 Sep 2.

Division of Urology, Cancer Prognostictables and Health Outcomes Unit, University of Montréal Health Center, Montreal, QC, Canada.

Purpose: To compare Cancer-specific mortality (CSM) in patients with Squamous cell carcinoma (SCC) vs. non-SCC penile cancer, since survival outcomes may differ between histological subtypes.

Methods: Within the Surveillance, Epidemiology and End Results database (2004-2016), penile cancer patients of all stages were identified. Temporal trend analyses, cumulative incidence and Kaplan-Meier plots, multivariable Cox regression and Fine and Gray competing-risks regression analyses tested for CSM differences between non-SCC vs. SCC penile cancer patients.

Results: Of 4,120 eligible penile cancer patients, 123 (3%) harbored non-SCC vs. 4,027 (97%) SCC. Of all non-SCC patients, 51 (41%) harbored melanomas, 42 (34%) basal cell carcinomas, 10 (8%) adenocarcinomas, eight (6.5%) skin appendage malignancies, six (5%) epithelial cell neoplasms, two (1.5%) neuroendocrine tumors, two (1.5%) lymphomas, two (1.5%) sarcomas. Stage at presentation differed between non-SCC vs. SCC. In temporal trend analyses, non-SCC diagnoses neither decreased nor increased over time (p > 0.05). After stratification according to localized, locally advanced, and metastatic stage, no CSM differences were observed between non-SCC vs. SCC, with 5-year survival rates of 11 vs 11% (p = 0.9) for localized, 33 vs. 37% (p = 0.4) for locally advanced, and 1-year survival rates of 37 vs. 53% (p = 0.9) for metastatic penile cancer, respectively. After propensity score matching for patient and tumor characteristics and additional multivariable adjustment, no CSM differences between non-SCC vs. SCC were observed.

Conclusion: Non-SCC penile cancer is rare. Although exceptions exist, on average, non-SCC penile cancer has comparable CSM as SCC penile cancer patients, after stratification for localized, locally invasive, and metastatic disease.
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http://dx.doi.org/10.1007/s10552-021-01493-3DOI Listing
September 2021

Feasibility and outcome of radical prostatectomy following inductive neoadjuvant therapy in patients with suspicion of rectal infiltration.

Urol Oncol 2021 Aug 26. Epub 2021 Aug 26.

Department of Urology, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt am Main, Germany.

Objective: To determine the feasibility and outcome of radical prostatectomy (RP) following neoadjuvant therapy (NAT) in patients with initial inoperable, rectum-infiltrating cT4 prostate cancer (PCa).

Methods: From 01/2018 to 12/2020, 26 patients with clinical (DRE) or radiographical (mpMRI) suspicion of rectum infiltrating PCa at diagnosis and NAT prior to RP were retrospectively identified from our prospective institutional database. Two patients were still inoperable after NAT. Downsizing was administered for at least 20 weeks and RP was performed after excluding ongoing rectal infiltration.

Results: At diagnosis, median PSA was 42.5 ng/ml (IQR: 23.0-66.1). Inductive NAT consisted of androgen deprivation therapy (ADT) in combination with chemotherapy (n = 9) or without chemotherapy (n = 14). Median preoperative PSA was 0.93 ng/ml (IQR: 0.24-0.40). Median time from NAT to RP was 6 months (IQR: 5-7). Two patients were still inoperable after NAT. Of 24 patients undergoing RP, abortion of surgery due to inoperability was observed in 2 patients (8.4%), demonstrating a total failure rate of NAT in 4 out of 26 patients (15.4%). One patient suffered a rectal injury with consecutive colostomy (4.2%). No Clavien-Dindo complication Grade IV or V were observed. Urinary continence was achieved in 16 patients (84.2%). Sufficient erection for sexual intercourse was present in 2 patients (10.5%). All patients received adjuvant ADT with or without radiation therapy. Median PSA at 13 months was 0.08 ng/ml (IQR: 0.01-0.74).

Conclusion: RP of initially rectum infiltrating PCa is feasible and safe after inductive NAT, however complications rates tend to be higher compared to standard RP.
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http://dx.doi.org/10.1016/j.urolonc.2021.07.028DOI Listing
August 2021

Salvage Radical Prostatectomy for Radio-Recurrent Prostate Cancer: An Updated Systematic Review of Oncologic, Histopathologic and Functional Outcomes and Predictors of Good Response.

Curr Oncol 2021 07 29;28(4):2881-2892. Epub 2021 Jul 29.

Department of Urology, Medical University of Vienna, 1090 Vienna, Austria.

A valid treatment option for recurrence after definite radiotherapy (RT) for localized prostate cancer (PC) is salvage radical prostatectomy (SRP). However, data on SRP are scarce, possibly resulting in an underutilization. A systematic review was performed using MEDLINE (Pubmed), Embase, and Web of Science databases including studies published between January 1980 and April 2020. Overall, 23 English language articles including a total number of 2323 patients were selected according to PRISMA criteria. The overall median follow-up was 37.5 months (IQR 35.5-52.5). Biochemical-recurrence (BCR)-free probability ranged from 34% to 83% at five years, respectively, and from 31% to 37% at 10 years. Cancer specific survival (CSS) and overall survival (OS) ranged from 88.7% to 98% and 64% to 95% at five years and from 72% to 83% and 65% to 72% at 10 years, respectively. Positive surgical margins ranged from 14% to 45.8% and pathologic organ-confined disease was reported from 20% to 57%. The rate of pathologic > T2-disease ranged from 37% to 80% and pN1 disease differed between 0% to 78.4%. Pre-SRP PSA, pre-SRP Gleason Score (GS), pathologic stage after SRP, and pathologic lymph node involvement seemed to be the strongest prognostic factors for good outcomes. SRP provides accurate histopathological and functional outcomes, as well as durable cancer control. Careful patient counseling in a shared decision-making process is recommended.
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http://dx.doi.org/10.3390/curroncol28040252DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8395524PMC
July 2021

Clinical impact of whole-body 68Ga-PSMA I&T PET/CT: lesion frequency and added benefit in lower extremities.

Nuklearmedizin 2021 Dec 20;60(6):417-424. Epub 2021 Aug 20.

Department for Diagnostic and Interventional Radiology and Nuclear Medicine, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.

Aim: Few small-scaled studies performed systematic analysis of the benefits of extending prostate specific membrane antigen positron-emission tomography/ computed tomography (Ga-PSMA I&T PET/CT) to the lower extremities in prostate cancer (PCa) patients. We hypothesized that Ga-PSMA I&T PET/CT positive lesions are rare in lower extremities of prostate cancer (PCa) patients, the clinical implication is negligible and may therefore be omitted.

Methods: We retrospectively analyzed 1,068 PCa patients who received Ga-PSMA I&T PET/CT in a single institution (2016-2018). Of those, 285 (26.7%) were newly diagnosed, 529 (49.5%) had biochemical recurrence (BCR) and 254 (23.8%) were castration-resistant prostate cancer (CRPC) patients.

Results: Of 1,068 Ga-PSMA I&T PET/CTs, positive lesions in the lower extremities were identified in 6.9% patients (n=74). Positive lesions in the lower extremities were most common in CRPC patients (19.7%; n=50), followed by newly diagnosed (3.2%; n=9) and BCR (2.8%; n=15) PCa patients. Only 3 patients presented with exclusive lesions in the lower extremities, respectively 0.8% (n=2) in CRPC and 0.4% (n=1) in newly diagnosed PCa. Both CRPC (94.1%, n=47) and BCR (80.0%, n=12) patients with PSMA-positive lesions predominantly received systemic therapy.

Conclusion: Identification of lower extremities lesions with PSMA PET/CT is uncommon and exclusive lesions are rare. PSMA PET/CT findings of the lower extremities did not change therapy management. Thus, scanning of the lower extremities can be omitted in standard protocols.
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http://dx.doi.org/10.1055/a-1542-6064DOI Listing
December 2021

The effect of primary urological cancers on survival in men with secondary prostate cancer.

Prostate 2021 Nov 16;81(15):1149-1158. Epub 2021 Aug 16.

Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Québec, Canada.

Background: To test the effect of urological primary cancers (bladder, kidney, testis, upper tract, penile, urethral) on overall mortality (OM) after secondary prostate cancer (PCa).

Methods: Within the Surveillance, Epidemiology and End Results (SEER) database, patients with urological primary cancers and concomitant secondary PCa (diagnosed 2004-2016) were identified and were matched in 1:4 fashion with primary PCa controls. OM was compared between secondary and primary PCa patients and stratified according to primary urological cancer type, as well as to time interval between primary urological cancer versus secondary PCa diagnoses.

Results: We identified 5,987 patients with primary urological and secondary PCa (bladder, n = 3,287; kidney, n = 2,127; testis, n = 391; upper tract, n = 125; penile, n = 47; urethral, n = 10) versus 531,732 primary PCa patients. Except for small proportions of Gleason grade group and age at diagnosis, PCa characteristics between secondary and primary PCa were comparable. Conversely, proportions of secondary PCa patients which received radical prostatectomy were smaller (29.0 vs. 33.5%), while no local treatment rates were higher (34.2 vs. 26.3%). After 1:4 matching, secondary PCa patients exhibited worse OM than primary PCa patients, except for primary testis cancer. Here, no OM differences were recorded. Finally, subgroup analyses showed that the survival disadvantage of secondary PCa patients decreased with longer time interval since primary cancer diagnosis.

Conclusions: After detailed matching for PCa characteristics, secondary PCa patients exhibit worse survival, except for testis cancer patients. The survival disadvantage is attenuated, when secondary PCa diagnosis is made after longer time interval, since primary urological cancer diagnosis.
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http://dx.doi.org/10.1002/pros.24209DOI Listing
November 2021

Influence of Tumor Burden on Serum Prostate-Specific Antigen in Prostate Cancer Patients Undergoing Radical Prostatectomy.

Front Oncol 2021 29;11:656444. Epub 2021 Jul 29.

Department of Urology, University Hospital Frankfurt, Frankfurt am Main, Germany.

Objective: We aimed to assess the correlation between serum prostate-specific antigen (PSA) and tumor burden in prostate cancer (PCa) patients undergoing radical prostatectomy (RP), because estimation of tumor burden is of high value, e.g., in men undergoing RP or with biochemical recurrence after RP.

Patients And Methods: From January 2019 to June 2020, 179 consecutive PCa patients after RP with information on tumor and prostate weight were retrospectively identified from our prospective institutional RP database. Patients with preoperative systemic therapy (n=19), metastases (cM1, n=5), and locally progressed PCa (pT4 or pN1, n=50) were excluded from analyses. Histopathological features, including total weight of the prostate and specific tumor weight, were recorded by specialized uro-pathologists. Linear regression models were performed to evaluate the effect of PSA on tumor burden, measured by tumor weight after adjustment for patient and tumor characteristics.

Results: Overall, median preoperative PSA was 7.0 ng/ml (interquartile range [IQR]: 5.41-10) and median age at surgery was 66 years (IQR: 61-71). Median prostate weight was 34 g (IQR: 26-46) and median tumor weight was 3.7 g (IQR: 1.8-7.1), respectively. In multivariable linear regression analysis after adjustment for patients and tumor characteristics, a significant, positive correlation could be detected between preoperative PSA and tumor weight (coefficient [coef.]: 0.37, CI: 0.15-0.6, p=0.001), indicating a robust increase in PSA of almost 0.4 ng/ml per 1g tumor weight.

Conclusion: Preoperative PSA was significantly correlated with tumor weight in PCa patients undergoing RP, with an increase in PSA of almost 0.4 ng/ml per 1 g tumor weight. This might help to estimate both tumor burden before undergoing RP and in case of biochemical recurrence.
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http://dx.doi.org/10.3389/fonc.2021.656444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8358926PMC
July 2021

Median time to progression with TKI-based therapy after failure of immuno-oncology therapy in metastatic kidney cancer: A systematic review and meta-analysis.

Eur J Cancer 2021 09 12;155:245-255. Epub 2021 Aug 12.

Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Québec, Canada.

Background: The efficacy of tyrosine kinase inhibitor (TKI)-based therapy after previous immuno-oncology therapy (IO) failure has been addressed before. However, summary efficacy estimates have never been generated in these reports. We addressed this void.

Material And Methods: We systematically examined TKI efficacy after IO-failure and generated weighted median progression-free survival (PFS) estimates for Pazopanib, Axitinib, Cabozantinib, Sunitinib. A systematic review according to PRISMA was conducted. PubMed and abstracts were queried. Only studies proving median PFS were included. Weighted medians were computed for each TKI alternative.

Results: Of 245 articles, nine eligible studies were included in the current study with 952 analysed patients. Weighted PFS medians after any previous IO-based therapy were respectively 13.7 (range from 4.6 to 24.4), 8.1 (range from 4.7 to 13.2), 8.5 (range from 4.7 to 15.2) and 6.9 months (range from 2.9 to 11.6) for Pazopanib, Axitinib, Cabozantinib, Sunitinib. Specific second-line weighted PFS median was 14.8 months (range from 5.6 to 24.4), 10.1 months (range from 6.4 to 13.2), 8.7 months (range from 4.7 to 15.2) and 6.0 months (range from 2.9 to 8.0) for Pazopanib, Axitinib, Cabozantinib, Sunitinib, respectively, after first-line IO.

Conclusion: Pazopanib results in the longest weighted median PFS, after previous IO-failure, regardless of treatment line, as well as in specific second-line, post-first-line IO failure settings. Pending novel studies, Pazopanib appears to represent the most promising treatment option after prior IO.
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http://dx.doi.org/10.1016/j.ejca.2021.07.014DOI Listing
September 2021

A real-world comparison of docetaxel versus abiraterone acetate for metastatic hormone-sensitive prostate cancer.

Cancer Med 2021 Sep 10;10(18):6354-6364. Epub 2021 Aug 10.

Department of Urology and Pediatric Urology, University Medicine Mainz, Mainz, Germany.

Background: Docetaxel (D) or secondary hormonal therapy (SHT) each combined with androgen deprivation therapy (ADT) represent possible treatment options in males with metastasized hormone-sensitive prostate cancer (mHSPC). Real-world data comparing different protocols are lacking yet. Thus, our objective was to compare the efficacy and safety of abiraterone acetate (AA)+ADT versus D+ADT in mHSPC.

Methods: In a retrospective multicenter analysis including males with mHSPC treated with either of the aforementioned protocols, overall survival (OS), progression-free survival 1 (PFS1), and progression-free survival 2 (PFS2) were assessed for both cohorts. Median time to event was tested by Kaplan-Meier method and log-rank test. The Cox-proportional hazards model was used for univariate and multivariate regression analyses.

Results: Overall, 196 patients were included. The AA+ADT cohort had a longer PFS1 in the log-rank testing (23 vs. 13 mos., p < 0.001), a longer PFS2 (48 vs. 33 mos., p = 0.006), and longer OS (80 vs. 61 mos., p = 0.040). In the multivariate analyses AA+ADT outperformed D+ADT in terms of PFS1 (HR = 0.34, 95% CI = 0.183-0.623; p = 0.001) and PFS2 (HR = 0.33 95% CI = 0.128-0.827; p = 0.018), respectively, while OS and toxicity rate were similar between both groups.

Conclusions: AA+ADT is mainly associated with a similar efficacy and overall toxicity rate as D+ADT. Further prospective research is required for validation of the clinical value of the observed benefit of AA+ADT for progression-free end-points.
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http://dx.doi.org/10.1002/cam4.4184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8446402PMC
September 2021

Salvage therapy for prostate cancer after radical prostatectomy.

Nat Rev Urol 2021 Nov 6;18(11):643-668. Epub 2021 Aug 6.

Department of Radiation Oncology, UCLA, Los Angeles, CA, USA.

More than 40% of men with intermediate-risk or high-risk prostate cancer will experience a biochemical recurrence after radical prostatectomy. Clinical guidelines for the management of these patients largely focus on the use of salvage radiotherapy with or without systemic therapy. However, not all patients with biochemical recurrence will go on to develop metastases or die from their disease. The optimal pre-salvage therapy investigational workup for patients who experience biochemical recurrence should, therefore, include novel techniques such as PET imaging and genomic analysis of radical prostatectomy specimen tissue, as well as consideration of more traditional clinical variables such as PSA value, PSA kinetics, Gleason score and pathological stage of disease. In patients without metastatic disease, the only known curative intervention is salvage radiotherapy but, given the therapeutic burden of this treatment, importance must be placed on accurate timing of treatment, radiation dose, fractionation and field size. Systemic therapy also has a role in the salvage setting, both concurrently with radiotherapy and as salvage monotherapy.
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http://dx.doi.org/10.1038/s41585-021-00497-7DOI Listing
November 2021

PSMA PET predicts metastasis-free survival in the setting of salvage radiotherapy after radical prostatectomy.

Urol Oncol 2021 Jul 31. Epub 2021 Jul 31.

Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Québec, Canada; Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany. Electronic address:

Introduction: To evaluate the impact of PSMA PET (prostate specific membrane antigen positron emission tomography) findings prior to salvage radiotherapy (SRT) in recurrent prostate cancer (PCa) after radical prostatectomy (RP) on metastasis-free survival (MFS).

Patients And Methods: Between 01/2012 and 12/2018, 1,599 patients received SRT for biochemical recurrence after RP at our institution. Five-year MFS of "positive PSMA PET" (n = 49) vs. "negative PSMA PET" (n = 106) vs. "no PSMA PET" (n = 1,599) prior to SRT was determined. For all time to event analyses, uni- and multivariable Cox's proportional hazards models and univariable Kaplan-Meier analyses were applied, with a significance threshold of P < 0.05. Further 4:1 propensity score matching for patient, cancer and treatment characteristics was performed to account for residual differences between groups.

Results: Of PSMA PET patients, 106 patients exhibited "negative PSMA PET" (68.4%) and 49 exhibited "positive PSMA PET" (31.6%). Median PSA at recurrence did not differ between groups (0.2 ng/ml; P= 0.4). After 4:1 propensity score matching, 5-year MFS between "no PSMA PET" and "negative PSMA PET" was 94.4 vs. 93.0%, respectively (P = 0.8). For "no PSMA PET" versus "positive PSMA PET", 5-year MFS was significantly lower in "positive PSMA PET" (92.3 vs. 48.5%, respectively P < 0.0001). Finally, "positive PSMA PET" was independently associated with worse MFS compared to "no PSMA PET" after multivariable adjustment in the overall cohort (HR 13.8, CI 7.5-25.2, P < 0.001).

Conclusions: Locoregional positive PSMA PET findings in recurrent patients after RP are highly predictive of worse MFS in the setting of SRT.
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http://dx.doi.org/10.1016/j.urolonc.2021.06.008DOI Listing
July 2021

Nomogram Predicting Downgrading in National Comprehensive Cancer Network High-risk Prostate Cancer Patients Treated with Radical Prostatectomy.

Eur Urol Focus 2021 Jul 29. Epub 2021 Jul 29.

Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Québec, Canada.

Background: Some high-risk prostate cancer (PCa) patients may show more favorable Gleason pattern at radical prostatectomy (RP) than at biopsy.

Objective: To test whether downgrading could be predicted accurately.

Design, Setting, And Participants: Within the Surveillance, Epidemiology and End Results database (2010-2016), 6690 National Comprehensive Cancer Network (NCCN) high-risk PCa patients were identified.

Outcome Measurements And Statistical Analyses: We randomly split the overall cohort between development and validation cohorts (both n = 3345, 50%). Multivariable logistic regression models used biopsy Gleason, prostate-specific antigen, number of positive prostate biopsy cores, and cT stage to predict downgrading. Accuracy, calibration, and decision curve analysis (DCA) tested the model in the external validation cohort.

Results And Limitations: Of 6690 patients, 50.3% were downgraded at RP, and of 2315 patients with any biopsy pattern 5, 44.1% were downgraded to RP Gleason pattern ≤4 + 4. Downgrading rates were highest in biopsy Gleason pattern 5 + 5 (84.1%) and lowest in 3 + 4 (4.0%). In the validation cohort, the logistic regression model-derived nomogram predicted downgrading with 71.0% accuracy, with marginal departures (±3.3%) from ideal predictions in calibration. In DCA, a net benefit throughout all threshold probabilities was recorded, relative to treat-all or treat-none strategies and an algorithm based on an average downgrading rate of 50.3%. All steps were repeated in the subgroup with any biopsy Gleason pattern 5, to predict RP Gleason pattern ≤4 + 4. Here, a second nomogram (n = 2315) yielded 68.0% accuracy, maximal departures from ideal prediction of ±5.7%, and virtually the same DCA pattern as the main nomogram.

Conclusions: Downgrading affects half of all high-risk PCa patients. Its presence may be predicted accurately and may help with better treatment planning.

Patient Summary: Downgrading occurs in every second high-risk prostate cancer patients. The nomograms developed by us can predict these probabilities accurately.
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http://dx.doi.org/10.1016/j.euf.2021.07.008DOI Listing
July 2021

The impact of time to prostate specific antigen nadir on biochemical recurrence and mortality rates after radiation therapy for localized prostate cancer.

Urol Oncol 2021 Jul 26. Epub 2021 Jul 26.

Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Québec, Canada; Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany. Electronic address:

Purpose: To investigate the effect of time to prostate-specific antigen (PSA) nadir (TTN) after radiation therapy (RTx) for prostate cancer (PCa) on biochemical recurrence (BCR) and overall survival (OS) rates.

Patients And Methods: We analyzed 2,506 patients treated with RTx (external beam radiotherapy, brachytherapy or combinations) between years 2000 and 2021. Kaplan Meier and multivariable Cox regression models tested BCR-free survival and OS after stratification according to TTN (≤24 vs. 24.1-60 vs. >60 months). Similar analyses were performed after stratification according to absolute PSA values at nadir (<0.01 vs. 0.01-0.1 vs. 0.11-0.4 vs. >0.4 ng/ml). Finally, we repeated analyses after setting the time point of PSA nadir as the beginning of follow up in survival analyses.

Results: 10-year BCR-free survival rates were 55.5, 81.7 and 91.1% and OS rates were 71.5, 79.4 and 96.1% for TTN ≤24 months, 24.1 month-60 month and >60 months, respectively. Longer TTN was an independent predictor for BCR-free survival and OS (all P<0.001). However, after accounting for lead-time bias, in multivariable analyses, this association remained only significant for BCR-free survival (P≤0.03), but not for OS (P≥0.1). Finally, compared to a PSA nadir of <0.01 ng/ml, PSA nadir of 0.01-0.1 ng/ml, 0.11-0.4 ng/ml as well as >0.4 ng/ml were independent predictors for shorter BCR-free survival (P≤0.02), but not OS (P≥0.08).

Conclusion: Shorter time to TTN and high PSA values at nadir are indicative of early treatment failure (BCR) and OS. However, after accounting for lead-time bias, this effect only remained valid for BCR.
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http://dx.doi.org/10.1016/j.urolonc.2021.06.025DOI Listing
July 2021

Focal Therapy for Prostate Cancer: Complications and Their Treatment.

Front Surg 2021 12;8:696242. Epub 2021 Jul 12.

Department of Urology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.

Focal therapy is a modern alternative to selectively treat a specific part of the prostate harboring clinically significant disease while preserving the rest of the gland. The aim of this therapeutic approach is to retain the oncological benefit of active treatment and to minimize the side-effects of common radical treatments. The oncological effectiveness of focal therapy is yet to be proven in long-term robust trials. In contrast, the toxicity profile is well-established in randomized controlled trials and multiple robust prospective cohort studies. This narrative review summarizes the relevant evidence on complications and their management after focal therapy. When compared to whole gland treatments, focal therapy provides a substantial benefit in terms of adverse events reduction and preservation of genito-urinary function. The most common complications occur in the peri-operative period. Urinary tract infection and acute urinary retention can occur in up to 17% of patients, while dysuria and haematuria are more common. Urinary incontinence following focal therapy is very rare (0-5%), and the vast majority of patients recover in few weeks. Erectile dysfunction can occur after focal therapy in 0-46%: the baseline function and the ablation template are the most important factors predicting post-operative erectile dysfunction. Focal therapy in the salvage setting after external beam radiotherapy has a significantly higher rate of complications. Up to one man in 10 will present a severe complication.
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http://dx.doi.org/10.3389/fsurg.2021.696242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8311122PMC
July 2021

Assessment of the optimal number of positive biopsy cores to discriminate between cancer-specific mortality in high-risk versus very high-risk prostate cancer patients.

Prostate 2021 Oct 26;81(14):1055-1063. Epub 2021 Jul 26.

Division of Urology, Cancer Prognostics and Health Outcomes Unit, University of Montréal Health Center, Montréal, Québec, Canada.

Background: Number of positive prostate biopsy cores represents a key determinant between high versus very high-risk prostate cancer (PCa). We performed a critical appraisal of the association between the number of positive prostate biopsy cores and CSM in high versus very high-risk PCa.

Methods: Within Surveillance, Epidemiology, and End Results database (2010-2016), 13,836 high versus 20,359 very high-risk PCa patients were identified. Discrimination according to 11 different positive prostate biopsy core cut-offs (≥2-≥12) were tested in Kaplan-Meier, cumulative incidence, and multivariable Cox and competing risks regression models.

Results: Among 11 tested positive prostate biopsy core cut-offs, more than or equal to 8 (high-risk vs. very high-risk: n = 18,986 vs. n = 15,209, median prostate-specific antigen [PSA]: 10.6 vs. 16.8 ng/ml, <.001) yielded optimal discrimination and was closely followed by the established more than or equal to 5 cut-off (high-risk vs. very high-risk: n = 13,836 vs. n = 20,359, median PSA: 16.5 vs. 11.1 ng/ml, p < .001). Stratification according to more than or equal to 8 positive prostate biopsy cores resulted in CSM rates of 4.1 versus 14.2% (delta: 10.1%, multivariable hazard ratio: 2.2, p < .001) and stratification according to more than or equal to 5 positive prostate biopsy cores with CSM rates of 3.7 versus 11.9% (delta: 8.2%, multivariable hazard ratio: 2.0, p < .001) in respectively high versus very high-risk PCa.

Conclusions: The more than or equal to 8 positive prostate biopsy cores cutoff yielded optimal results. It was very closely followed by more than or equal to 5 positive prostate biopsy cores. In consequence, virtually the same endorsement may be made for either cutoff. However, more than or equal to 5 positive prostate biopsy cores cutoff, based on its existing wide implementation, might represent the optimal choice.
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http://dx.doi.org/10.1002/pros.24202DOI Listing
October 2021

Radiation Therapy After Radical Prostatectomy: What Has Changed Over Time?

Front Surg 2021 9;8:691473. Epub 2021 Jul 9.

Division of Oncology/Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy.

The role and timing of radiotherapy (RT) in prostate cancer (PCa) patients treated with radical prostatectomy (RP) remains controversial. While recent trials support the oncological safety of early salvage RT (SRT) compared to adjuvant RT (ART) in selected patients, previous randomized studies demonstrated that ART might improve recurrence-free survival in patients at high risk for local recurrence based on adverse pathology. Although ART might improve survival, this approach is characterized by a risk of overtreatment in up to 40% of cases. SRT is defined as the administration of RT to the prostatic bed and to the surrounding tissues in the patient with PSA recurrence after surgery but no evidence of distant metastatic disease. The delivery of salvage therapies exclusively in men who experience biochemical recurrence (BCR) has the potential advantage of reducing the risk of side effects without theoretically compromising outcomes. However, how to select patients at risk of progression who are more likely to benefit from a more aggressive treatment after RP, the exact timing of RT after RP, and the use of hormone therapy and its duration at the time of RT are still open issues. Moreover, what the role of novel imaging techniques and genomic classifiers are in identifying the most optimal post-operative management of PCa patients treated with RP is yet to be clarified. This narrative review summarizes most relevant published data to guide a multidisciplinary team in selecting appropriate candidates for post-prostatectomy radiation therapy.
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http://dx.doi.org/10.3389/fsurg.2021.691473DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8298897PMC
July 2021

Reply to Benefit-harm ratio of the diagnostic workup in patients with prostate cancer of Gleason score from 9 to 10.

Cancer 2021 Nov 23;127(22):4312. Epub 2021 Jul 23.

Radiation Oncology, Brigham and Women's Hospital, Boston, Massachusetts.

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http://dx.doi.org/10.1002/cncr.33813DOI Listing
November 2021
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