A small but meaningful percentage of men who are treated with external beam radiation therapy for prostate cancer will develop late gastrointestinal toxicity. While numerous strategies to prevent gastrointestinal injury have been studied, clinical trials concentrating on late toxicity have been difficult to carry out. Identification of subjects at high risk for late gastrointestinal injury could allow toxicity prevention trials to be performed using reasonable sample sizes. Acute radiation therapy toxicity has been shown to predict late toxicity in several organ systems. Late toxicities may occur as a consequential effect of acute injury. In this systematic review of published reports, we found that late gastrointestinal toxicity following prostate radiotherapy seems to be statistically and potentially causally related to acute gastrointestinal morbidity as a consequential effect. We submit that acute gastrointestinal toxicity may be used to identify at-risk patients who may benefit from additional attention for medical interventions and close follow-up to prevent late toxicity. Acute gastrointestinal toxicity could also be explored as a surrogate endpoint for late effects in prospective trials.

Matthew Sean Peach

Timothy N. Showalter

Nitin Ohri

Systematic Review of the Relationship between Acute and Late Gastrointestinal Toxicity after Radiotherapy for Prostate Cancer

<i>Purpose</i>. Atypical small acinar proliferation (ASAP) is diagnosed in 1-2&#x25; of prostate biopsies. 30&#x2013;40&#x25; of patients with ASAP may be diagnosed with prostate cancer (PCa) on repeat biopsy. Our objective was to examine the association between ASAP and subsequent diagnosis of intermediate/high risk PCa. <i>Materials and Methods</i>. Ninety-six patients who underwent prostate biopsy from 2000 to 2013 and were diagnosed with ASAP were identified. Clinicopathologic features were analyzed. Comparison was made between those with subsequent PCa on repeat biopsy and those with benign repeat pathology. <i>Results</i>. 56/96 (58&#x25;) patients had a repeat biopsy. 22/56 (39&#x25;) were subsequently diagnosed with PCa. There was no significant difference in patients&#x2019; characteristics. Presence of HGPIN on initial biopsy was associated with a benign repeat biopsy (68&#x25; versus 23&#x25;). 17/22 (77&#x25;) had Gleason grade (GG) 3+3 disease and only 5/22 (23&#x25;) had GG 3+4 disease. <i>Conclusions</i>. 22/56 patients (39&#x25;) of patients who underwent a subsequent prostate biopsy following a diagnosis of ASAP were found to have PCa. 77&#x25; of these men were diagnosed with GG 3+3 PCa. Only 23&#x25; were found to have intermediate risk PCa and no high risk PCa was identified. Immediate repeat prostate biopsy in patients diagnosed with ASAP may be safely delayed. A multi-institutional cohort is being analyzed.

Andrew Leone

Katherine Rotker

Christi Butler

Anthony Mega

Jianhong Li

Ali Amin

Stephen F. Schiff

Gyan Pareek

Dragan Golijanin

Joseph F. Renzulli

Atypical Small Acinar Proliferation: Repeat Biopsy and Detection of High Grade Prostate Cancer

<i>Background</i>. Prostate cancer is the most common noncutaneous cancer and second leading cause of cancer-related mortality in men in the US. Growing evidence suggests that oxidative stress is involved in prostate cancer.<i> Methods</i>. In this study, thioredoxin 1 (Trx 1), an enzyme and subcellular indicator of redox status, was measured in prostate biopsy tissue from 55 men from the North Carolina-Louisiana Prostate Cancer Project. A pathologist blindly scored levels of Trx 1. The association between Trx 1 and the Gleason score, erythrocyte antioxidant enzyme activity, and dietary antioxidant intake was determined using Fisher&#x2019;s exact test.<i> Results</i>. Trx 1 levels in benign prostate tissue in men with incident prostate cancer were positively associated with the Gleason score (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.2064009pt" id="M1" height="8.8423pt" version="1.1" viewBox="-0.0498162 -8.6359 44.8393 8.8423" width="44.8393pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-81" d="M600 480C600 590 528 650 384 650H143L137 622C222 614 225 607 210 531L130 127C113 41 106 36 23 28L17 0H294L300 28C204 36 195 42 212 127L243 284L314 263C327 263 339 263 352 264C465 271 600 337 600 480ZM508 481C508 351 402 304 329 304C289 304 265 311 250 317L295 559C302 594 310 606 323 611C335 616 350 619 367 619C455 619 508 573 508 481Z"/></g><g transform="matrix(.013,0,0,-0.013,11.658,0)"><path id="g117-34" d="M535 323V373H52V323H535ZM535 138V188H52V138H535Z"/></g><g transform="matrix(.013,0,0,-0.013,22.921,0)"><path id="g113-49" d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z"/></g><g transform="matrix(.013,0,0,-0.013,29.161,0)"><path id="g113-47" d="M113 -12C146 -12 170 11 170 46C170 78 146 103 114 103S58 78 58 46C58 11 82 -12 113 -12Z"/></g><g transform="matrix(.013,0,0,-0.013,32.125,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.365,0)"><path id="g113-50" d="M384 0V27C293 34 287 42 287 114V635C232 613 172 594 109 583V559L157 557C201 555 205 550 205 499V114C205 42 199 34 109 27V0H384Z"/></g></svg>) and inversely associated with dietary antioxidant intake (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.2064009pt" id="M2" height="8.8423pt" version="1.1" viewBox="-0.0498162 -8.6359 44.8393 8.8423" width="44.8393pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-81"/></g><g transform="matrix(.013,0,0,-0.013,11.658,0)"><use xlink:href="#g117-34"/></g><g transform="matrix(.013,0,0,-0.013,22.921,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,29.161,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,32.125,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.365,0)"><path id="g113-52" d="M285 378C315 398 338 416 353 432C373 451 384 474 384 503C384 579 325 635 236 635H235C182 635 136 610 108 579L65 516L85 496C110 533 150 575 205 575C258 575 300 543 300 481C300 407 232 369 141 339L147 310C163 315 188 321 211 321C268 321 338 284 338 192C338 94 288 40 217 40C160 40 119 68 93 91C85 98 77 97 69 91C60 84 47 71 46 58C44 46 48 35 62 22C75 10 116 -12 162 -12C234 -12 424 62 424 224C424 297 373 359 285 376V378Z"/></g></svg>). In prostate cancer tissue, Trx 1 levels were associated with erythrocyte glutathione peroxidase activity (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.2064009pt" id="M3" height="8.8423pt" version="1.1" viewBox="-0.0498162 -8.6359 44.8393 8.8423" width="44.8393pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-81"/></g><g transform="matrix(.013,0,0,-0.013,11.658,0)"><use xlink:href="#g117-34"/></g><g transform="matrix(.013,0,0,-0.013,22.921,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,29.161,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,32.125,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.365,0)"><use xlink:href="#g113-50"/></g></svg>). No association was found for other erythrocyte enzymes. Greater Gleason score of malignant tissue corresponds to a greater difference in Trx 1 levels between malignant and benign tissue (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.2064009pt" id="M4" height="8.8423pt" version="1.1" viewBox="-0.0498162 -8.6359 44.8393 8.8423" width="44.8393pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-81"/></g><g transform="matrix(.013,0,0,-0.013,11.658,0)"><use xlink:href="#g117-34"/></g><g transform="matrix(.013,0,0,-0.013,22.921,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,29.161,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,32.125,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.365,0)"><path id="g113-53" d="M456 178V225H360V632H320C217 496 115 347 20 206V178H280V106C280 40 276 34 189 27V0H445V27C364 34 360 39 360 106V178H456ZM280 225H82C149 335 214 431 278 520H280V225Z"/></g></svg>).<i> Conclusion</i>. These results suggest that the redox status of prostate tissue is associated with prostate cancer grade and both endogenous and exogenous antioxidants.

Terrence M. Vance

Gissou Azabdaftari

Elena A. Pop

Sang Gil Lee

L. Joseph Su

Elizabeth T. H. Fontham

Jeannette T. Bensen

Susan E. Steck

Lenore Arab

James L. Mohler

Ming-Hui Chen

Sung I. Koo

Ock K. Chun

Thioredoxin 1 in Prostate Tissue Is Associated with Gleason Score, Erythrocyte Antioxidant Enzyme Activity, and Dietary Antioxidants

Genome-wide association studies (GWAS) have implicated single nucleotide polymorphisms (SNPs) on chromosomes 2p15, 6q25, 7p15.2, 7q21, 8q24, 10q11, 10q26, 11q13, 17q12, 17q24, 19q13, and Xp11, with prostate cancer (PCa) susceptibility and/or tumour aggressiveness, in populations of African, European, and Asian ancestry. The objective of this study was to confirm these associations in South African Mixed Ancestry and White men. We evaluated 17 prioritised GWAS SNPs in South African cases (331 Mixed Ancestry and 155 White) and controls (178 Mixed Ancestry and 145 White). The replicated SNP associations for the different South African ethnic groups were rs7008482 (8q24) (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-3.4294pt" id="M1" height="14.8655pt" version="1.1" viewBox="-0.0498162 -11.4361 81.0509 14.8655" width="81.0509pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-113" d="M570 304C570 398 525 448 414 448C385 448 343 445 312 434L329 511L321 518C297 504 262 482 244 460L233 411C195 397 159 381 128 358L135 332C160 347 189 360 224 373L111 -147C97 -210 84 -218 17 -231L13 -257L254 -247L259 -218L233 -216C183 -212 177 -202 189 -142L218 -1C238 -10 266 -12 283 -12C351 3 429 48 483 105C543 168 570 242 570 304ZM482 289C482 161 380 33 304 33C278 33 248 51 233 69L303 396C326 400 352 403 369 403C428 403 482 380 482 289Z"/></g><g transform="matrix(.013,0,0,-0.013,11.342,0)"><path id="g117-34" d="M535 323V373H52V323H535ZM535 138V188H52V138H535Z"/></g><g transform="matrix(.013,0,0,-0.013,22.605,0)"><path id="g113-51" d="M412 140C382 77 369 73 315 73H129L270 222C362 320 402 379 402 466C402 571 322 635 234 635C177 635 130 609 99 576L42 495L64 475C90 514 133 568 201 568C274 568 318 519 318 435C318 349 255 267 193 193C144 135 87 78 32 23V0H405C417 45 427 89 440 131L412 140Z"/></g><g transform="matrix(.013,0,0,-0.013,28.845,0)"><path id="g113-47" d="M113 -12C146 -12 170 11 170 46C170 78 146 103 114 103S58 78 58 46C58 11 82 -12 113 -12Z"/></g><g transform="matrix(.013,0,0,-0.013,31.809,0)"><path id="g113-53" d="M456 178V225H360V632H320C217 496 115 347 20 206V178H280V106C280 40 276 34 189 27V0H445V27C364 34 360 39 360 106V178H456ZM280 225H82C149 335 214 431 278 520H280V225Z"/></g><g transform="matrix(.013,0,0,-0.013,38.049,0)"><path id="g113-54" d="M153 550H386L412 615L406 623H120L82 318C104 327 142 338 184 338C294 338 347 275 347 187C347 112 305 39 221 39C160 39 119 71 97 89C88 97 80 96 71 90C59 80 50 67 49 57C48 45 52 36 66 23C80 9 123 -12 169 -12C221 -11 288 15 342 59C403 109 431 165 431 225C431 308 366 395 238 395C212 395 165 379 127 364L153 550Z"/></g><g transform="matrix(.013,0,0,-0.013,47.195,0)"><path id="g117-42" d="M528 54L331 254L528 455L492 493L294 291L96 493L60 455L257 254L60 54L96 16L294 217L492 16L528 54Z"/></g><g transform="matrix(.013,0,0,-0.013,57.731,0)"><path id="g113-50" d="M384 0V27C293 34 287 42 287 114V635C232 613 172 594 109 583V559L157 557C201 555 205 550 205 499V114C205 42 199 34 109 27V0H384Z"/></g><g transform="matrix(.013,0,0,-0.013,63.971,0)"><path id="g113-49" d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z"/></g><g transform="matrix(.0091,0,0,-0.0091,70.258,-5.741)"><path id="g54-33" d="M556 236V289H56V236H556Z"/></g><g transform="matrix(.0091,0,0,-0.0091,75.818,-5.741)"><path id="g50-54" d="M158 548H390L417 615L410 623H122L83 318C105 326 143 337 185 337C296 337 350 275 350 188C350 116 308 42 225 42C164 42 122 74 100 93C90 101 82 99 72 92C60 82 51 68 50 59C48 46 52 38 66 24C82 9 125 -12 172 -12C225 -11 292 15 346 59C408 108 437 166 437 226C437 309 371 397 242 397C214 397 170 382 133 369L158 548Z"/></g></svg>), rs6983267 (8q24) (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-3.4294pt" id="M2" height="14.8655pt" version="1.1" viewBox="-0.0498162 -11.4361 81.0509 14.8655" width="81.0509pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-113"/></g><g transform="matrix(.013,0,0,-0.013,11.342,0)"><use xlink:href="#g117-34"/></g><g transform="matrix(.013,0,0,-0.013,22.605,0)"><use xlink:href="#g113-53"/></g><g transform="matrix(.013,0,0,-0.013,28.845,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,31.809,0)"><use xlink:href="#g113-53"/></g><g transform="matrix(.013,0,0,-0.013,38.049,0)"><path id="g113-57" d="M249 635C141 635 70 555 70 471C70 401 114 353 179 316C143 294 106 267 90 252C68 231 45 202 45 157C45 50 130 -12 237 -12C322 -12 435 52 435 169C435 256 372 304 303 343C349 374 375 398 383 407C401 429 411 458 411 487C411 569 344 635 249 635ZM238 603C285 603 337 567 337 482C337 422 310 385 276 358C205 393 145 426 145 500C145 552 179 603 238 603ZM248 20C183 20 125 70 125 163C125 218 158 268 206 300C284 261 355 217 355 143C355 66 308 20 248 20Z"/></g><g transform="matrix(.013,0,0,-0.013,47.195,0)"><use xlink:href="#g117-42"/></g><g transform="matrix(.013,0,0,-0.013,57.731,0)"><use xlink:href="#g113-50"/></g><g transform="matrix(.013,0,0,-0.013,63.971,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.0091,0,0,-0.0091,70.258,-5.741)"><use xlink:href="#g54-33"/></g><g transform="matrix(.0091,0,0,-0.0091,75.818,-5.741)"><path id="g50-56" d="M453 623H65C60 580 56 530 46 472H80C103 538 110 548 175 548H389C310 380 195 168 90 0L98 -12L175 -2C273 206 366 408 462 610L453 623Z"/></g></svg>), and rs10993994 (10q11) (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-3.429399pt" id="M3" height="15.0208pt" version="1.1" viewBox="-0.0498162 -11.5914 81.0509 15.0208" width="81.0509pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-113"/></g><g transform="matrix(.013,0,0,-0.013,11.342,0)"><use xlink:href="#g117-34"/></g><g transform="matrix(.013,0,0,-0.013,22.605,0)"><use xlink:href="#g113-50"/></g><g transform="matrix(.013,0,0,-0.013,28.845,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,31.809,0)"><use xlink:href="#g113-53"/></g><g transform="matrix(.013,0,0,-0.013,38.049,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,47.195,0)"><use xlink:href="#g117-42"/></g><g transform="matrix(.013,0,0,-0.013,57.731,0)"><use xlink:href="#g113-50"/></g><g transform="matrix(.013,0,0,-0.013,63.971,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.0091,0,0,-0.0091,70.258,-5.741)"><use xlink:href="#g54-33"/></g><g transform="matrix(.0091,0,0,-0.0091,75.818,-5.741)"><path id="g50-52" d="M290 377C321 398 342 415 358 430C378 450 389 473 389 502C389 578 329 635 238 635H237C184 635 137 610 109 578L64 515L88 493C112 529 154 573 208 573S303 542 303 482C303 409 233 370 141 341L149 308C165 313 190 319 215 319C272 319 341 283 341 193C342 98 292 43 222 43C163 43 122 72 96 94C88 101 79 100 70 94C61 87 47 73 46 60C44 47 48 37 62 23C76 10 118 -12 165 -12C238 -12 430 62 430 223C430 297 379 359 290 375V377Z"/></g></svg>) in Mixed Ancestry men and rs10993994 (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-3.429399pt" id="M4" height="15.0208pt" version="1.1" viewBox="-0.0498162 -11.5914 81.0509 15.0208" width="81.0509pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-113"/></g><g transform="matrix(.013,0,0,-0.013,11.342,0)"><use xlink:href="#g117-34"/></g><g transform="matrix(.013,0,0,-0.013,22.605,0)"><use xlink:href="#g113-50"/></g><g transform="matrix(.013,0,0,-0.013,28.845,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,31.809,0)"><use xlink:href="#g113-54"/></g><g transform="matrix(.013,0,0,-0.013,38.049,0)"><path id="g113-55" d="M137 343C167 482 260 545 321 574C357 591 397 603 429 609L423 641C382 634 335 622 295 608C189 570 37 457 37 238C37 84 125 -12 242 -12C362 -12 447 89 447 209C447 311 374 393 267 393C247 393 226 386 204 376L137 343ZM227 337C318 337 361 256 361 173C361 105 336 22 258 22C176 22 126 120 126 240C126 266 127 291 132 310C155 323 189 337 227 337Z"/></g><g transform="matrix(.013,0,0,-0.013,47.195,0)"><use xlink:href="#g117-42"/></g><g transform="matrix(.013,0,0,-0.013,57.731,0)"><use xlink:href="#g113-50"/></g><g transform="matrix(.013,0,0,-0.013,63.971,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.0091,0,0,-0.0091,70.258,-5.741)"><use xlink:href="#g54-33"/></g><g transform="matrix(.0091,0,0,-0.0091,75.818,-5.741)"><path id="g50-58" d="M247 635C116 635 39 518 39 421C39 315 113 237 221 237C239 237 258 241 281 253L349 289C315 140 204 42 60 19L66 -15C90 -15 153 -5 207 16C344 70 447 199 447 385C447 521 373 635 247 635ZM231 598C329 598 356 478 356 390C356 371 355 347 352 325C330 309 297 297 262 297C179 297 127 369 127 456C127 515 156 598 231 598Z"/></g></svg>) in White men. No significant associations were observed for the analyses stratified by disease aggressiveness in the individual and the combined population group analysis. The present study demonstrates that a number of known PCa susceptibility variants may contribute to disease susceptibility in South African men. Larger genetic investigations extended to other South African population groups are warranted to confirm the role of these and other SNPs in disease susceptibility.

Pedro Fernandez

Muneeb Salie

Danielle du Toit

Andre van der Merwe

Analysis of Prostate Cancer Susceptibility Variants in South African Men: Replicating Associations on Chromosomes 8q24 and 10q11

<i>Objective</i>. To describe urologists&#x2019; practice patterns when managing patients with advanced prostate cancer (PCa) in Spain. <i>Methods</i>. This was an observational study conducted by 120 urologists using retrospective data of advanced PCa patients attending hospitals and outpatient centers. <i>Results</i>. Urologists evaluated a total of 375 patients (mean age: 75 years; ECOG 0-1: 77&#x25;; mean serum PSA levels at study entry: 50.5&#x2009;ng/Ml). Approximately 50&#x25; of patients had bone metastases, and 60.6&#x25; experienced pain as the main symptom of progressive disease. Primary androgen deprivation therapy (ADT) use was 99.7&#x25;, with continuous ADT as the dominant strategy (91.9&#x25;). After failure of initial ADT, antiandrogen withdrawal was the next method most commonly used in 57&#x25; of patients. Choice of secondary hormonal treatment was made mostly by urologists (96&#x25;), who continued to monitor patients. Patient follow-up after chemotherapy and supportive care were mainly done in urology units, although responsibility was shared with medical oncologists and radiologists. <i>Conclusion</i>. The urologists&#x2019; attitudes towards management of PCa in the routine practice in Spain show the urologist as an integral component even when patients progress to advanced stages of the disease.

Maria Jos&#xe9; Ribal

Juan Ignacio Mart&#xed;nez-Salamanca

Camilo Garc&#xed;a Freire

Current Patterns of Management of Advanced Prostate Cancer in Routine Clinical Practice in Spain

<i>Purpose.</i> Experimental data suggest that tumour cells can reversibly transition between epithelial and mesenchymal states (EMT and MET), a phenomenon known as cellular plasticity. The aim of this review was to appraise the clinical evidence for the role of cellular plasticity in prostate cancer (PC) bone metastasis.<i> Methods.</i> An electronic search was performed using PubMed for studies that have examined the differential expression of epithelial, mesenchymal, and stem cell markers in human PC bone metastasis tissues.<i> Results.</i> The review included nineteen studies. More than 60&#x25; of the studies used &#x2264;20 bone metastasis samples, and there were several sources of heterogeneity between studies. Overall, most stem cell markers analysed, except for CXCR4, were positively expressed in bone metastasis tissues, while the expression of EMT and MET markers was heterogeneous between and within samples. Several EMT and stemness markers that are involved in osteomimicry, such as Notch, Met receptor, and Wnt/<i>&#x3b2;</i> pathway, were highly expressed in bone metastases.<i> Conclusions.</i> Clinical findings support the role of cellular plasticity in PC bone metastasis and suggest that epithelial and mesenchymal states cannot be taken in isolation when targeting PC bone metastasis. The paper also highlights several challenges in the clinical detection of cellular plasticity.

Dima Y. Jadaan

Mutaz M. Jadaan

John P. McCabe

Cellular Plasticity in Prostate Cancer Bone Metastasis

<i>Introduction</i>. Prostate cancer is the most common cancer among men in USA. The surgical outcomes of prostate cancer remain inconsistent. Barriers such as socioeconomic factors may play a role in patients&#x2019; decision of refusing recommended cancer-directed surgery. <i>Methods</i>. The Nebraska Cancer Registry data was used to calculate the proportion of prostate cancer patients recommended the cancer-directed surgery and the surgery refusal rate. Multivariate logistic regression was applied to analyze the socioeconomic indicators that were related to the refusal of surgery. <i>Results</i>. From 1995 to 2012, 14,876 prostate cancer patients were recommended to undergo the cancer-directed surgery in Nebraska, and 576 of them refused the surgery. The overall refusal rate of surgery was 3.9&#x25; over the 18 years. Patients with early-stage prostate cancer were more likely to refuse the surgery. Patients who were Black, single, or covered by Medicaid/Medicare had increased odds of refusing the surgery. <i>Conclusion</i>. Socioeconomic factors were related to the refusal of recommended surgical treatment for prostate cancer. Such barriers should be addressed to improve the utilization of surgical treatment and patients&#x2019; well-being.

K. M. Islam

Jiajun Wen

Prostate Cancer Patients&#x2019; Refusal of Cancer-Directed Surgery: A Statewide Analysis

<i>Background</i>. New nontoxic targeted approaches are needed for patients with castrate resistant prostate cancer (CRPC). Our preclinical studies show that activated T cells (ATC) armed with anti-CD3 x anti-Her2 bispecific antibody (Her2Bi) kill prostate cancer cells lines, induce a Th<sub>1</sub> cytokine pattern upon engagement of tumor cells, prevent the development of prostate tumors, and retard tumor growth in immunodeficient mice. These studies provided strong rationale for our phase I dose-escalation pilot study to test ATC armed with Her2Bi (aATC) for safety in men with CRPC. <i>Methods</i>. Seven of 8 men with CRPC were evaluable after receiving two infusions per week for 4 weeks. The men received 2.5, 5 or 10 &#xd7; 10<sup>9</sup> aATC per infusion with low dose interleukin-2 and granulocyte-macrophage colony stimulating factor. <i>Results</i>. There were no dose limiting toxicities, and there was 1 partial responder and 3 of 7 patients had significant decreases in their PSA levels and pain scores. Immune evaluations of peripheral blood mononuclear cells in 2 patients before and after immunotherapy showed increases in IFN-<i>&#x3b3;</i> EliSpot responses and Th<sub>1</sub> serum cytokines. <i>Conclusions</i>. These results provide a strong rationale for developing phase II trials to determine whether aATC are effective for treating CRPC.

Ulka Vaishampayan

Archana Thakur

Ritesh Rathore

Nicola Kouttab

Lawrence G. Lum

Phase I Study of Anti-CD3 x Anti-Her2 Bispecific Antibody in Metastatic Castrate Resistant Prostate Cancer Patients

This prospective, noninterventional, open-label, multicentre, Belgian study assessed the prevalence of moderate to severe lower urinary tract symptoms (LUTS) in patients with locally advanced or metastatic prostate cancer scheduled to receive triptorelin therapy and its effects on LUTS were evaluated focusing on symptom relief and changes in quality of life (QOL) related to urinary symptoms (November 2006 to May 2010). Inclusion criteria were age &#x3e;18 years, histologically confirmed advanced or metastatic prostate cancer, and life expectancy &#x2265;12 months. Exclusion criteria were treatment with any LHRH analogue within the last 6 months or any other investigational agent within the last 3 months before study entry. Patients who received one or more triptorelin doses and had one or more efficacy assessments were evaluated. In total, 325 patients were included with a median age of 74 years (50 to 95 years). Mean age at first diagnosis was <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.3625803pt" id="M1" height="9.06134pt" version="1.1" viewBox="-0.0498162 -8.69876 33.7208 9.06134" width="33.7208pt"><g transform="matrix(.0135,0,0,-0.0135,0,0)"><path id="g113-56" d="M447 623H65C61 580 56 530 47 475H76C100 541 106 550 172 550H388C308 376 196 170 91 -1L98 -12L172 -2C268 204 360 408 455 611L447 623Z"/></g><g transform="matrix(.0135,0,0,-0.0135,6.505,0)"><path id="g113-52" d="M285 378C315 398 338 416 353 432C373 451 384 474 384 503C384 579 325 635 236 635H235C182 635 136 610 108 579L65 516L85 496C110 533 150 575 205 575C258 575 300 543 300 481C300 407 232 369 141 339L147 310C163 315 188 321 211 321C268 321 338 284 338 192C338 94 288 40 217 40C160 40 119 68 93 91C85 98 77 97 69 91C60 84 47 71 46 58C44 46 48 35 62 22C75 10 116 -12 162 -12C234 -12 424 62 424 224C424 297 373 359 285 376V378Z"/></g><g transform="matrix(.0135,0,0,-0.0135,16.037,0)"><path id="g117-37" d="M535 290V340H323V533H265V340H52V290H265V84H323V290H535ZM535 -22V28H52V-22H535Z"/></g><g transform="matrix(.0135,0,0,-0.0135,27.018,0)"><path id="g113-57" d="M249 635C141 635 70 555 70 471C70 401 114 353 179 316C143 294 106 267 90 252C68 231 45 202 45 157C45 50 130 -12 237 -12C322 -12 435 52 435 169C435 256 372 304 303 343C349 374 375 398 383 407C401 429 411 458 411 487C411 569 344 635 249 635ZM238 603C285 603 337 567 337 482C337 422 310 385 276 358C205 393 145 426 145 500C145 552 179 603 238 603ZM248 20C183 20 125 70 125 163C125 218 158 268 206 300C284 261 355 217 355 143C355 66 308 20 248 20Z"/></g></svg> years. Moderate (IPSS 8&#x2013;19) to severe (IPSS &#x2265; 20) LUTS were observed in 62&#x25; of patients. Triptorelin reduced LUTS severity. This improvement was perceived within the first 24 weeks of treatment and was maintained after 48 weeks. A decrease in PSA level was also observed.

Alexandre Peltier

Fouad Aoun

Vincent De Ruyter

Patrick Cabri

Roland Van Velthoven

Triptorelin in the Relief of Lower Urinary Tract Symptoms in Advanced Prostate Cancer Patients: The RESULT Study

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<p><em>Prostate Cancer</em> provides a multidisciplinary platform for scientists, surgeons, oncologists and clinicians working on prostate cancer. Research includes diagnosis, surgery, radiotherapy, drug discovery and medical management of the disease.</p>


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Prostate Cancer provides a multidisciplinary platform for scientists, surgeons, oncologists and clinicians working on prostate cancer. Research includes diagnosis, surgery, radiotherapy, drug discovery and medical management of the disease.

Prostate Cancer