Quantitative Histomorphometric Features of Prostate Cancer Predict Patients Who Biochemically Recur Following Prostatectomy.

Prostate cancer is the most commonly diagnosed cancer in men, accounting for 27% of the new male cancer diagnoses in 2022. If organ-confined, removal of the prostate through radical prostatectomy is considered curative; however, distant metastases may occur, resulting in a poor patient prognosis. This study sought to determine whether quantitative pathomic features of prostate cancer differ in patients who biochemically experience biological recurrence after surgery. Whole-mount prostate histology from 78 patients was analyzed for this study. In total, 614 slides were hematoxylin and eosin stained and digitized to produce whole slide images (WSI). Regions of differing Gleason patterns were digitally annotated by a genitourinary fellowship-trained pathologist, and high-resolution tiles were extracted from each annotated region of interest for further analysis. Individual glands within the prostate were identified using automated image processing algorithms, and histomorphometric features were calculated on a per-tile basis and across WSI and averaged by patients. Tiles were organized into cancer and benign tissues. Logistic regression models were fit to assess the predictive value of the calculated pathomic features across tile groups and WSI; additionally, models using clinical information were used for comparisons. Logistic regression classified each pathomic feature model at accuracies >80% with areas under the curve of 0.82, 0.76, 0.75, and 0.72 for all tiles, cancer only, noncancer only, and across WSI. This was comparable with standard clinical information, Gleason Grade Groups, and CAPRA score, which achieved similar accuracies but areas under the curve of 0.80, 0.77, and 0.70, respectively. This study demonstrates that the use of quantitative pathomic features calculated from digital histology of prostate cancer may provide clinicians with additional information beyond the traditional qualitative pathologist assessment. Further research is warranted to determine possible inclusion in treatment guidance.

Cystectomy and Urinary Diversion for the Management of a Devastated Lower Urinary Tract Following Prostatic Cryotherapy and/or Radiotherapy.

INTRODUCTION: We investigated the outcomes and quality of life measures in men who underwent cystectomy and urinary diversion for devastating lower urinary tract toxicity after prostatic radiotherapy and/or cryotherapy for the treatment of prostate cancer. METHODS: Records of patients who underwent cystectomy and urinary diversion for the management of a devastated lower urinary tract following prostatic radiotherapy or cryotherapy were reviewed retrospectively. A postoperative, retrospective quality of life (QOL) survey was designed specific to this patient subset and obtained by telephone interview. RESULTS: Extirpative surgery with urinary diversion for management of a devastated lower urinary tract was performed on 15 patients with a mean age of 72 years (range 63-82). Toxicities leading to bladder removal included bladder neck contractures, prostatic necrosis, incontinence, osteomyelitis, bladder calculi, fistulae, urethral strictures, abscesses, necrotizing fasciitis, and radiation/hemorrhagic cystitis. The mean number of failed conservative, minimally invasive interventions per patients prior to cystectomy was 3.7 (range 1-12). The average time period from major complication following radiotherapy/cryotherapy to cystectomy was 29.1 months (range 5-65). The QOL survey showed all of the patients who completed the survey (n = 13) would undergo the procedure again and 11 (85%) would have undergone the procedure an average of 13.2 months sooner (range 5-36). CONCLUSION: Toxicities secondary to prostatic radiotherapy or cryotherapy may be debilitating. Our results demonstrate that cystectomy with urinary diversion can improve QOL in patients with a devastated lower urinary tract.

T2-Weighted MRI Radiomic Features Predict Prostate Cancer Presence and Eventual Biochemical Recurrence.

Prostate cancer (PCa) is the most diagnosed non-cutaneous cancer in men. Despite therapies such as radical prostatectomy, which is considered curative, distant metastases may form, resulting in biochemical recurrence (BCR). This study used radiomic features calculated from multi-parametric magnetic resonance imaging (MP-MRI) to evaluate their ability to predict BCR and PCa presence. Data from a total of 279 patients, of which 46 experienced BCR, undergoing MP-MRI prior to surgery were assessed for this study. After surgery, the prostate was sectioned using patient-specific 3D-printed slicing jigs modeled using the T2-weighted imaging (T2WI). Sectioned tissue was stained, digitized, and annotated by a GU-fellowship trained pathologist for cancer presence. Digitized slides and annotations were co-registered to the T2WI and radiomic features were calculated across the whole prostate and cancerous lesions. A tree regression model was fitted to assess the ability of radiomic features to predict BCR, and a tree classification model was fitted with the same radiomic features to classify regions of cancer. We found that 10 radiomic features predicted eventual BCR with an AUC of 0.97 and classified cancer at an accuracy of 89.9%. This study showcases the application of a radiomic feature-based tool to screen for the presence of prostate cancer and assess patient prognosis, as determined by biochemical recurrence.

Diffusion Restriction Comparison between Gleason 4 Fused Glands and Cribriform Glands within Patient Using Whole-Mount Prostate Pathology as Ground Truth.

The presence and extent of cribriform patterned Gleason 4 (G4) glands are associated with poor prognosis following radical prostatectomy. This study used whole-mount prostate histology and multiparametric magnetic resonance imaging (MP-MRI) to evaluate diffusion differences in G4 gland morphology. Fourty-eight patients underwent MP-MRI prior to prostatectomy, of whom 22 patients had regions of both G4 cribriform glands and G4 fused glands (G4CG and G4FG, respectively). After surgery, the prostate was sliced using custom, patient-specific 3D-printed slicing jigs modeled according to the T2-weighted MR image, processed, and embedded in paraffin. Whole-mount hematoxylin and eosin-stained slides were annotated by our urologic pathologist and digitally contoured to differentiate the lumen, epithelium, and stroma. Digitized slides were co-registered to the T2-weighted MRI scan. Linear mixed models were fitted to the MP-MRI data to consider the different hierarchical structures at the patient and slide level. We found that Gleason 4 cribriform glands were more diffusion-restricted than fused glands.

Second-Generation Jak2 Inhibitors for Advanced Prostate Cancer: Are We Ready for Clinical Development?

Androgen deprivation therapy (ADT) for metastatic and high-risk prostate cancer (PC) inhibits growth pathways driven by the androgen receptor (AR). Over time, ADT leads to the emergence of lethal castrate-resistant PC (CRPC), which is consistently caused by an acquired ability of tumors to re-activate AR. This has led to the development of second-generation anti-androgens that more effectively antagonize AR, such as enzalutamide (ENZ). However, the resistance of CRPC to ENZ develops rapidly. Studies utilizing preclinical models of PC have established that inhibition of the Jak2-Stat5 signaling leads to extensive PC cell apoptosis and decreased tumor growth. In large clinical cohorts, Jak2-Stat5 activity predicts PC progression and recurrence. Recently, Jak2-Stat5 signaling was demonstrated to induce ENZ-resistant PC growth in preclinical PC models, further emphasizing the importance of Jak2-Stat5 for therapeutic targeting for advanced PC. The discovery of the Jak2V617F somatic mutation in myeloproliferative disorders triggered the rapid development of Jak1/2-specific inhibitors for a variety of myeloproliferative and auto-immune disorders as well as hematological malignancies. Here, we review Jak2 inhibitors targeting the mutated Jak2V617F vs. wild type (WT)-Jak2 that are currently in the development pipeline. Among these 35 compounds with documented Jak2 inhibitory activity, those with potency against WT-Jak2 hold strong potential for advanced PC therapy.

Oncological efficacy and safety of nephron-sparing surgery for selected patients with locally advanced renal cell carcinoma.

OBJECTIVE: To evaluate perioperative complication rates, recurrence-free and cancer-specific survival (CSS) in a large group of matched patients who had nephron-sparing surgery (NSS) or radical nephrectomy (RN) for pT2-T3bN0M0 renal cell carcinoma (RCC). PATIENTS AND METHODS: With approval from the institutional review board, the institutional nephrectomy database of 3470 patients treated at the authors' institution from 1990 to 2006 was searched for patients who had NSS or RN for unilateral, sporadic, pathological T2-T3bN0M0 RCC. Patients with non-metastatic, node-negative RCC and a follow-up of >/=6 months were included in the analysis. RESULTS: In all, 601 patients treated with RN (567) or NSS (34) for pT2-T3bN0M0 RCC and a mean (median, range) follow-up of 43.4 (31.8, 6.1-172.6) and 62.1 (37.5, 7.0-192.0) months, respectively, met the study inclusion criteria. Disease recurred in four of 34 (12%) patients treated with NSS and in 164/567 (28.9%) managed with RN at a median of 24.2 and 13.2 months, respectively. There were no local recurrences among patients treated with NSS. On multivariate Cox proportional-hazards regression analysis, when adjusted for the effects of stage, grade, size and tumour histology, procedure type (NSS vs RN) was not an independent predictor of disease recurrence or RCC-specific death. Patients treated with NSS had a higher procedure-related complication rate, but similar estimated intraoperative blood loss, transfusion rate, equal duration of surgical procedure and hospital stay compared with patients managed with RN. CONCLUSION: In highly selected patients with locally advanced RCC, NSS is safe and provides oncological outcomes equivalent to patients managed with RN.

Adjuvant therapy for renal cell carcinoma.

In 2006, approximately 38,890 patients in the United States will be diagnosed with kidney tumors. Roughly 90% of those will be renal cell carcinomas (RCCs). Of those patients, 30% will have metastatic disease at the time of diagnosis. An additional 20% to 30% with clinically localized disease at the time of nephrectomy will subsequently develop metastatic disease for which there are few reliable, effective treatments. In 2006, no clinically proven, adjuvant therapy exists for patients at high risk of relapse following definitive surgical therapy. In the past, several strategies have been tried unsuccessfully in the adjuvant setting, including, radiotherapy, chemotherapy, immunotherapy, and hormonal therapy. An improved understanding of the molecular basis of RCC has allowed for a more targeted approach to therapy. Several newer agents, including thalidomide, vitespin (heat shock protein [hsp] 96 vaccine), WX-G250, sorafenib, and sunitinib, are either currently under investigation in the adjuvant setting or being considered for future adjuvant trials. Here, we discuss the past, present, and future of adjuvant therapy for RCC patients at high risk for relapse following definitive surgical therapy.

Duloxetine for the treatment of post-prostatectomy stress urinary incontinence.

OBJECTIVES: Stress urinary incontinence (SUI) is a known complication following prostatectomy. Duloxetine, a combined serotonin/norepinephrine reuptake inhibitor, can decrease SUI by increasing urethral sphincter contractility. We examined the outcomes of patients with mild to moderate post-prostatectomy SUI treated with duloxetine. METHODS: We conducted a retrospective review of men treated with duloxetine to manage mild to moderate post-prostatectomy SUI from 2006 to 2012. All patients received oral duloxetine 30 mg once a week, then 60 mg thereafter. Patients were seen one month later to determine drug efficacy and side effects. RESULTS: In total, 94 men were included in the study. Daily pad usage decreased from 2.9 (range: 1-5) to 1.6 (range: 0-4) (p < 0.05). Incontinence Impact Questionnaire (IIQ-7) scores decreased from 13.0 (range: 6-18) to 7.9 (range: 2-16) (p < 0.05). Linear satisfaction scores improved from 0.8 (range: 0-2) to 2.0 (range: 1-3) (p < 0.05). Following a 1-month duloxetine trial, 33/94 (35%) men reported satisfactory SUI improvement and requested to continue the medication. The drug was discontinued in 61/94 (65%) patients due to poor efficacy in 32/94 (34%), intolerable side effects in 14/94 (15%) or both in 15/94 (16%). Reported side effects included fatigue, light-headedness, insomnia, nausea and dry mouth. CONCLUSIONS: Duloxetine improved post-prostatectomy SUI in 47/94 (50%) men following a 1-month trial. However, only 33/94 (35%) patients were able to tolerate the drug. Duloxetine may be considered a treatment option for men with mild to moderate post-prostatectomy SUI.

Robotic-assisted endoscopic inguinal lymphadenectomy.

INTRODUCTION: Open inguinal lymphadenectomy is a well-established therapeutic and diagnostic option for patients with invasive penile squamous cell carcinoma who are at risk of regional and distant metastases. We report the use of endoscopic robotic-assisted bilateral inguinal lymph node dissections in a patient with palpable inguinal nodes despite oral antibiotics. TECHNIQUE: A 2-cm mid-thigh incision was made to develop a plane just deep to Camper's (fatty) fascia. Once a sufficient working space was created to place 3 robotic ports and 1 assistant port, subcutaneous gas was instilled, and the robotic device was docked and used to perform the dissection. The surgical approach replicated the principles of open techniques such that the contents of the femoral canal were dissected to the inguinal ligament superiorly, the sartorius muscle laterally, and the adductor longus muscle medially to include both superficial and deep lymph nodes in the dissection template. CONCLUSIONS: To our knowledge, this is the first report of an endoscopic robotic-assisted inguinal lymph node dissection. A minimally invasive approach circumventing the need for thick skin flaps, the improved flexibility afforded by robotic instruments, and the improved magnification could decrease the morbidity associated with inguinal lymphadenectomy while maintaining oncologic principles.

Is radiofrequency ablation safe for solitary kidneys?

OBJECTIVES: To determine the safety of radiofrequency ablation (RFA) in patients with a solitary kidney. METHODS: We retrospectively reviewed the charts of all patients undergoing RFA at our institution for treatment of solid renal tumors and identified those with a solitary kidney. The clinical and radiographic characteristics were evaluated, including renal function, length of stay, use of blood products, and complications. The serum creatinine level and creatinine clearance rates were determined at baseline, within 1 week, and at the last follow-up visit. RESULTS: Of the 100 patients who were treated with RFA for solid renal tumors from September 2001 to January 2006, 16 with a solitary kidney were identified. The mean patient age was 66.5 years, and the mean tumor size was 3.4 cm. The median preoperative creatinine level was 1.4 mg/dL. The median percentage of change in creatinine clearance within 1 week of ablation was 13.3% and at a mean follow-up duration of 15.3 months was 9.1%. All kidneys functioned postoperatively. All but 1 patient had maintained their renal function at the last follow-up visit. Major acute complications occurred in 4 patients and consisted of 3 cases of clot obstruction that were readily treated with ureteral stenting and 1 case of perinephric hemorrhage. CONCLUSIONS: RFA appears to maintain adequate renal function in select patients with a solitary kidney. When treating patients with central tumors in a solitary kidney, the urologist should be vigilant with regard to the need for ureteral stent placement with the onset of any hematuria.

Validation of criteria used to predict extraprostatic cancer extension: a tool for use in selecting patients for nerve sparing radical prostatectomy.

PURPOSE: We have previously reported that a prostate biopsy core specimen with a tumor length of at least 7 mm plus any positive basal biopsy core is the best predictor of extraprostatic extension (EPE) in radical prostatectomy (RP) specimens. We present prospectively collected data to validate our results. MATERIALS AND METHODS: The study included 270 patients who underwent RP for localized prostate cancer between January 2002 and December 2003 by a single surgeon. We correlated side specific biopsy data, pretreatment prostate specific antigen, clinical stage and RP type using pathological specimen data. RESULTS: Mean patient age was 59.6 years and median prostate specific antigen was 8.24 ng/ml. Of the patients 94 (35%) underwent unilateral and 114 (42%) underwent bilateral nerve sparing RP. The overall incidence of EPE was 16%. The incidence of EPE was 33% in patients who met our criteria vs 4.6% in those who did not. Of 538 evaluable sides 7.2% were positive at the surgical margin. The incidence of ipsilateral positive margins was 2.5% when the neurovascular bundle was spared according to our criteria vs 11.8% when the bundle was resected according to criteria. CONCLUSIONS: This series validates our finding that a prostate biopsy core with a tumor length of at least 7 mm plus a positive basal biopsy core of any length and tumor grade is predictive of ipsilateral EPE. In the absence of these criteria the incidence of ipsilateral positive margins is low. Thus, these criteria are valuable for predicting EPE and selecting patients for nerve sparing RP.

Penile calciphylaxis.

Calciphylaxis is an uncommon condition usually seen in patients with end-stage renal disease. The typical features include violaceous skin lesions overlying painful, indurated, subcutaneous nodules. Necrosis and nonhealing ulcers, with secondary gangrene, sepsis, and death frequently follow. The outpatient hemodialysis population has a reported calciphylaxis prevalence of 1% to 4.1%; however, published studies contain only a few case reports of penile calciphylaxis. The urologic presentation consists primarily of penile gangrene. A description of our patient, the underlying pathologic features, a review of the relevant published studies, and the possible predisposing conditions are included.