Prostate Cancer: Symptoms, Diagnosis & Treatment - 2nd Volume

This report aims to shed light on the intricate challenges encountered during the diagnosis and treatment of an uncommon variant of prostate cancer—mixed adenosquamous cell carcinoma of the prostate. Prostate cancers of this nature pose distinctive diagnostic and therapeutic dilemmas due to their rarity and complex histological composition. We present a case of a 63-year-old man with metastatic prostate cancer, featuring adenocarcinoma with squamous cell differentiation, who underwent a multimodal treatment approach. The patient responded to first-line carboplatin, docetaxel, and androgen deprivation therapy, followed by androgen receptor pathway inhibitor (ARPI) maintenance. However, disease progression led to radiation therapy and a subsequent switch to Lutetium (177Lu) vipivotide tetraxetan after chemotherapy challenges. Comprehensive genetic profiling revealed shared mutations in the prostate and liver lesions, emphasizing the role of targeted therapies. Prostate-specific membrane antigen (PSMA)-targeted therapy resulted in a notable PSA decline. This case highlights the evolving treatment landscape for rare prostate cancers, integrating genetic insights for tailored interventions. In conclusion, squamous cell carcinoma (SCC) of the prostate is rare, emphasizing the imperative for enhanced comprehension in diagnosis and management. Our case suggests the potential efficacy of ARPI and PSMA-targeted therapies. Our findings advocate for a more nuanced approach to the management of this rare prostate cancer variant, leveraging genomic insights for personalized treatment strategies. This exploration serves as a foundation for further research and clinical considerations in addressing the challenges posed by mixed adenosquamous cell carcinoma of the prostate. Full article

Background: The gastrin-releasing peptide receptor (GRPr) is highly overexpressed in several solid tumors, including treatment-naïve and recurrent prostate cancer. [⁶⁸Ga]Ga-RM2 is a well-established radiotracer for PET imaging of GRPr, and [¹⁷⁷Lu]Lu-RM2 has been proposed as a therapeutic alternative for patients with heterogeneous and/or low expression of PSMA. In this study, we aimed to evaluate the expression of GRPr and PSMA in a group of patients diagnosed with castration-resistant prostate cancer (mCRPC) by means of PET imaging. Methods: Seventeen mCRPC patients referred for radio-ligand therapy (RLT) were enrolled and underwent [⁶⁸Ga]Ga-PSMA-11 and [⁶⁸Ga]Ga-RM2 PET/CT imaging, 8.8 ± 8.6 days apart, to compare the biodistribution of each tracer. Uptake in healthy organs and tumor lesions was assessed by SUV values, and tumor-to-background ratios were analyzed. Results: [⁶⁸Ga]Ga-PSMA-11 showed significantly higher uptake in tumor lesions in bone, lymph nodes, prostate, and soft tissues and detected 23% more lesions compared to [⁶⁸Ga]Ga-RM2. In 4/17 patients (23.5%), the biodistribution of both tracers was comparable. Conclusions: Our results show that in our cohort of mCRPC patients, PSMA expression was higher compared to GRPr. Nevertheless, RLT with [¹⁷⁷Lu]Lu-RM2 may be an alternative treatment option for selected patients or patients in earlier disease stages, such as biochemical recurrence. Full article

Background: Radical prostatectomy by lateral approach allows performing a prostatectomy through a buttonhole, with direct access to the seminal vesicle and fully sparing the anterior pubovesical complex. Our aim is to show the results of reproducing the technique of robotic radical prostatectomy by lateral approach, in terms of intraoperative, postoperative, oncological and functional parameters. Methods: We analyzed 513 patients submitted to robotic radical prostatectomy by lateral approach from January 2015 to March 2021, operated on by two surgeons in our institution. The oncological and functional results of both surgeons were compared. Results: When comparing both surgeons, the rate of positive surgical margins (PSM) was 32.87% and 37.9% and significant surgical margins (PSM > 2 mm) were 5.88% and 7.58% (p = 0.672) for surgeon 1 and surgeon 2, respectively. Immediate continence was 86% and 85% and sexual potency at one year 73% and 72%, with a similar rate of complications for surgeon 1 and 2. Conclusions: Radical prostatectomy by the lateral approach technique with preservation of the anterior pubovesical complex is reproducible and offers good oncological and functional results. Full article

Background: Despite recent awareness of institutional racism, there are still important racial disparities in prostate cancer medical research. We investigated the historical development of research on racial disparities and bias. Methods: PubMed was searched for the term ‘prostate cancer race’ and added key terms associated with racial disparity. As an indicator of scientific interest in the topic, we analyzed whether the number of publications increased linearly as an indicator of growing interest. The linearity is expressed as R². Results: The general search term “prostate cancer race” yielded 4507 publications. More specific search terms with ≥12 publications showing a higher scientific interest were found after 2005. The terms with the most publications when added to the general term were “genetic” (n = 1011), “PSA” (n = 995), and “detection” (n = 861). There was a linear increase in publications for “prostate cancer race” (R² = 0.75) since 1980. Specific terms added to the general terms with a high linear increase (R² ≥ 0.7) were “screening” (R² = 0.82), “detection” (R² = 0.72), “treatment access” (R² = 0.71), and “trial underrepresentation” (R² = 0.71). However, only a few studies have investigated its association with sexual activity. A combination with “sexual” showed 157 publications but only two years with ≥12 publications/year. Conclusion: The terms “genetic”, “PSA”, and “detection” have been the focus of recent research on racial differences in prostate cancer. We found that old stereotypes are still being mentioned but seem to find little interest in the current literature. Further research interest was found in “treatment access”. Recently, interest in socioeconomic factors has decreased. Full article

Klotho proteins, αKlotho, βKlotho, and γKlotho, exert tumor-suppressive activities via the fibroblast growth factor receptors and multiple cell-signaling pathways. There is a growing interest in Klotho proteins as potential diagnostic and prognostic biomarkers for multiple diseases. However, recent advances regarding their roles and potential applications in cancer remain disperse and require an integrated analysis. The present review analyzed research articles published between 2012 and 2022 in the Cochrane and Scopus scientific databases to study the role of Klotho in cancer and their potential as tools for diagnosing specific cancer types, predicting tumor aggressiveness and prognosis. Twenty-six articles were selected, dealing with acute myeloid leukemia and with bladder, breast, colorectal, esophageal, gastric, hepatocellular, ovarian, pancreatic, prostatic, pulmonary, renal, and thyroid cancers. αKlotho was consistently associated with improved prognosis and may be useful in estimating patient survival. A single study reported the use of soluble αKlotho levels in blood serum as a tool to aid the diagnosis of esophageal cancer. γKlotho was associated with increased aggressiveness of bladder, breast, and prostate cancer, and βKlotho showed mixed results. Further clinical development of Klotho-based assays will require careful identification of specific tumor subtypes where Klotho proteins may be most valuable as diagnostic or prognostic tools. Full article

Prostate motion (standard deviation, range of motion, and diffusion coefficient) was calculated from 4D ultrasound data of 1791 fractions of radiation therapy in N = 100 patients. The inner diameter of the lesser pelvis was obtained from transversal slices through the pubic symphysis in planning CTs. On the lateral and craniocaudal axes, motility increases significantly (t-test, p < 0.005) with the inner diameter of the lesser pelvis. A diameter of >106 mm (ca. 6th decile) is a good predictor for high prostate intrafraction motion (ca. 9th decile). The corresponding area under the receiver operator curve (AUROC) is 80% in the lateral direction, 68% to 80% in the craniocaudal direction, and 62% to 70% in the vertical direction. On the lateral x-axis, the proposed test is 100% sensitive and has a 100% negative predictive value for all three characteristics (standard deviation, range of motion, and diffusion coefficient). On the craniocaudal z-axis, the proposed test is 79% to 100% sensitive and reaches 95% to 100% negative predictive value. On the vertical axis, the proposed test still delivers 98% negative predictive value but is not particularly sensitive. Overall, the proposed predictor is able to help identify patients at risk of high prostate motion based on a single planning CT. Full article

High-risk human papillomavirus (HPV) is etiologically related to cervical cancer, other anogenital cancers and oropharyngeal carcinomas. Low-risk HPV, especially HPV6 and HPV11, cause genital warts and laryngeal papillomas. However, the accumulating data suggests that HPV6 and HPV11 may cause malignant lesions at non-cervical anatomic sites. This review aims to estimate the proportions of single and dual HPV6/11 infections in multiple cancers reported in the last 10 years in the Cochrane, Embasa and PubMed databases. Secondly, the genomes of HPV6/11 were compared with the most common high-risk genotype, HPV16, to determine the similarities and differences. A total of 11 articles were selected, including between one and 334 HPV+ cancer patients. The frequencies of single or dual HPV6/11 infections ranged between 0–5.5% for penile and 0–87.5% for laryngeal cancers and were null for vulvar, vaginal and oral cancers. The genomic similarities between HPV6/11 and HPV16 mainly involved the E7 gene, indicating a limited ability to block cell differentiation. The presence of single or dual HPV6/11 infections in variable proportions of penile and laryngeal cancers support the vaccination strategies that cover these genotypes, not only for preventing genital warts but also for cancer prevention. Other risk factors and co-carcinogens are likely to participate in epithelial carcinogenesis associated with low-risk HPV. Full article

The role of prostate cryoablation was still uncertain for patients with high-risk prostate cancer (PC). This study was designed to investigate 10-year disease-free survival and establish a nomogram in localized high-risk PC patients. Between October 2008 and December 2020, 191 patients with high-risk PC who received primary total prostate cryoablation (PTPC) were enrolled. The primary endpoint was biochemical recurrence (BCR), defined using Phoenix criteria. The performance of pre-operative and peri-operative nomograms was determined using the Harrell concordance index (C-index). Among the cohort, the median age and PSA levels at diagnosis were 71 years and 12.3 ng/mL, respectively. Gleason sum 8–10, stage ≥ T3a, and PSA > 20 ng/mL were noted in 27.2%, 74.4%, and 26.2% of patients, respectively. During the median follow-up duration of 120.4 months, BCR-free rates at 1, 3, 5, and 10 years were 92.6%, 76.6%, 66.7%, and 50.8%, respectively. The metastasis-free, cancer-specific, and overall survival rates were 89.5%, 97.4%, and 90.5% at 10 years, respectively. The variables in the pre-operative nomogram for BCR contained PSA at diagnosis, clinical stage, and Gleason score (C-index: 0.73, 95% CI, 0.67–0.79). The variables in the peri-operative nomogram for BCR included PSA at diagnosis, Gleason score, number of cryoprobes used, and PSA nadir (C-index: 0.83, 95% CI, 0.78–0.88). In conclusion, total prostate cryoablation appears to be an effective treatment option for selected men with high-risk PC. A pre-operative nomogram can help select patients suitable for cryoablation. A peri-operative nomogram signifies the importance of the ample use of cryoprobes and helps identify patients who may need early salvage treatment. Full article

Background: The aim of this study was to determine the false negative rates of prebiopsy magnetic resonance imaging (MRI) and MRI–ultrasound (US) 12-core systematic prostate biopsy (PBx) by analyzing radical prostatectomy specimens. Methods: This retrospective study included 3600 prostate cancer (PCa) patients who underwent robot-assisted laparoscopic radical prostatectomy. Based on comparison of lobe-specific data on final pathology with preoperative biopsy and imaging data, the study population was subdivided into group I—contralateral (CL) benign PBx (n = 983), group II—CL and/or bilateral (BL) non-suspicious mpMRI (n = 2223) and group III—CL benign PBx + non-suspicious mpMRI (n = 688). This population was studied for the presence of PCa, clinically significant PCa (csPCa), extracapsular extension (ECE) (pathological stage pT3), positive frozen section and final positive surgical margin (PSM) in the CL lobe. Descriptive statistics were performed. Results: In subgroups I, II and III, PCa was respectively detected in 21.5%, 37.7% and 19.5% of cases, and csPCa in 11.3%, 16.3% and 10.3% of cases. CL pT3 disease was seen in 4.5%, 4% and 5.5%, and CL surgical margins and/or frozen section analysis were positive in 6%, 7% and 5% of cases in subgroups I, II and III, respectively. Conclusions: There are still significant rates of false negatives in the standard care diagnostics of PCa. Further strategies are required to improve the accuracy of diagnosis and determination of tumor location. Full article

Purpose: To analyse diagnostic and therapeutic impact of molecular imaging TNM (miTNM) stage obtained with [¹⁸F]DCFPyL versus [¹⁸F]F-choline in head-to-head comparison in biochemical recurrence (BCR) of prostate cancer (PCa). Material and methods: Patients with BCR of PCa after radical treatment with previous [¹⁸F]F-choline-PET/CT (negative or oligometastatic disease) were recruited to [¹⁸F]DCFPyL-PET/CT. Patients were classified according to: grade group, European Association of Urology classification, PSA, PSA doubling time (PSAdt) and PSA velocity (PSAvel). The overall detection rate (DR) and miTNM stage according to PROMISE criteria were assessed for both radiotracers and also correlated (Kappa). The influence of PSA and kinetics on both PET/CT (DR and miTNM) and predictive value of unfavourable kinetics on miTNM were determined. Cut-off PSA, PSAdt and PSAvel values able to predict PET/CT results were determined. Change in miTNM and treatment derived from [¹⁸F]DCFPyL information compared with [¹⁸F]F-choline were also evaluated. Results: We studied 138 patients. [¹⁸F]DCFPyL showed a higher DR than [¹⁸F]F-choline (64.5% versus 33.3%) with a fair agreement. [¹⁸F]DCFPyL and [¹⁸F]F-choline detected T in 33.3% versus 19.6%, N in 27.5% versus 13.8%, and M in 30.4% versus 8.7%. Both tracers’ DR showed significant associations with PSA and PSAvel. Significant association was only found between miTNM and PSA on [¹⁸F]F-choline-PET/CT (p = 0.033). For [¹⁸F]F-choline and [¹⁸F]DCFPyL-PET/CT, a PSAdt cut-off of 4.09 and 5.59 months, respectively, were able to predict M stage. [¹⁸F]DCFPyL changed therapeutic management in 40/138 patients. Conclusions: [¹⁸F]DCFPyL provides a higher DR and superior miTNM staging than [¹⁸F]F-choline in restaging BCR, especially with high PSA and unfavourable PSA kinetics, showing a fair agreement to [¹⁸F]F-choline. Full article

Nowadays, in the case of suspected prostate cancer (PCa), tissue needle biopsy remains the benchmark for diagnosis despite its invasiveness and poor tolerability, as serum prostate-specific antigen (PSA) is limited by low specificity. The aim of this proteomic study was to identify new diagnostic biomarkers in urine, an easily and non-invasively available sample, able to selectively discriminate cancer from benign prostatic hyperplasia (BPH), evaluating whether the presence of inflammation may be a confounding parameter. The analysis was performed by two-dimensional gel electrophoresis (2-DE), mass spectrometry (LC-MS/MS) and Enzyme-Linked Immunosorbent Assay (ELISA) on urine samples from PCa and BPH patients, divided into subgroups based on the presence or absence of inflammation. Significant quantitative and qualitative differences were found in the urinary proteomic profile of PCa and BPH groups. Of the nine differentially expressed proteins, only five can properly be considered potential biomarkers of PCa able to discriminate the two diseases, as they were not affected by the inflammatory process. Therefore, the proteomic research of novel and reliable urinary biomarkers of PCa should be conducted considering the presence of inflammation as a realistic interfering element, as it could hinder the detection of important protein targets. Full article

Prostate cancer is the second most common form of cancer in men and the fifth leading cause of death among men worldwide. Men with metastatic castration-resistant prostate cancer (mCRPC) often have BRCA-1 or BRCA-2 gene mutations which can make them sensitive to poly-(ADP-ribose) polymerase inhibitors or PARP inhibitors (PARPi), such as Olaparib, Rucaparib, and Niraparib. Although significant advances have been made with PARPi and the prognosis of patients with mCRPC has improved dramatically, resistance often constitutes a challenge that frequently results in tumor escape. This present communication paper explores the role of PARPi in BRCA-positive prostate cancer and sheds light on numerous published and ongoing clinical trials that will determine the future of PARPi at various tumor stages as a monotherapy or polytherapy regime. Full article

[¹⁷⁷Lu]Ludotadipep, which enables targeted delivery of beta-particle radiation to prostate tumor cells, had been suggested as a promising therapeutic option for mCRPC. From November 2020 to March 2022, a total of 30 patients were enrolled for single dose of [¹⁷⁷Lu]Ludotadipep RPT, 6 subjects in each of the 5 different activity groups of 1.9 GBq, 2.8 GBq, 3.7 GBq, 4.6 GBq, and 5.6 GBq. [¹⁷⁷Lu]Ludotadipep was administered via venous injection, and patients were hospitalized for three days to monitor for any adverse effects. Serum PSA levels were followed up at weeks 1, 2, 3, 4, 6, 8, and 12, and PSMA PET/CT with [¹⁸F]Florastamin was obtained at baseline and again at weeks 4 and 8. The subjects required positive PSMA PET/CT prior to [¹⁷⁷Lu]Ludotadipep administration. Among the 29 subjects who received [¹⁷⁷Lu]Ludotadipep, 36 treatment emergent adverse events (TEAEs) occurred in 17 subjects (58.6%) and 4 adverse drug reactions (ADRs) in 3 subjects (10.3%). Of the total 24 subjects who had full 12-week follow-up data, 16 (66.7%) showed decrease in PSA of any magnitude, and 9 (37.5%) showed a decrease in PSA by 50% or greater. A total of 5 of the 24 patients (20.8%) showed disease progression (PSA increase of 25% or higher from the baseline) at the 12th week following single dose of [¹⁷⁷Lu]Ludotadipep. These data thus far suggest that [¹⁷⁷Lu]Ludotadipep could be a promising RPT agent with low toxicity in mCRPC patients who have not been responsive to conventional treatments. Full article

Objectives: Prostate cancer is well known to express high levels of somatostatin receptors and preliminary data suggests that PET imaging with the somatostatin analog, [⁶⁸Ga]Ga-DOTATATE, may allow for whole body staging of patients with metastatic castration resistant prostate cancer (mCRPC) and neuroendocrine prostate cancer (NePC). This study explores the utility of [⁶⁸Ga]Ga-DOTATATE PET-CT to identify metastatic deposits in men with mCRPC and NePC and prognosticate disease progression. Methods: [⁶⁸Ga]Ga-DOTATATE PET-CT was performed in 17 patients with mCRPC and of those, 2/17 had NePC. A semiquantitative analysis with standardized uptake values (SUV) (e.g., SUVmax, SUVmean) was performed for each metastatic lesion and reference background tissues. [⁶⁸Ga]Ga-DOTATATE uptake in metastatic deposits was further classified as: mild (less than liver), moderate (up to liver average), or marked (greater than liver). Serial prostate-specific antigen measurements and patient survival were followed up to 3 years after PET imaging to assess response to standard of care treatment. Results: All patients had at least one metastatic lesion with identifiable [⁶⁸Ga]Ga-DOTATATE uptake. Marked [⁶⁸Ga]Ga-DOTATATE uptake was found in 7/17 patients, including both NePC patients, and all were non-responders to systemic therapy and died within the follow up period, with a mean time to death of 8.1 months. Three patients had mild [⁶⁸Ga]Ga-DOTATATE uptake, and all were responders to systemic therapy and were alive 36 months after [⁶⁸Ga]Ga-DOTATATE imaging. Conclusions: [⁶⁸Ga]Ga-DOTATATE is able to identify mCRPC and NePC metastatic deposits, and lesions with [⁶⁸Ga]Ga-DOTATATE uptake > liver may portend poor outcomes in patients with mCRPC. Full article

Objective: To analyze the perioperative outcomes of neoadjuvant hormone therapy (NHT) before laparoscopic and robot-assisted surgery for localized high-risk prostate cancer in a Chinese cohort. Methods: The clinical data of 385 patients with localized high-risk prostate cancer who underwent radical prostatectomy (RP) in our hospital from January 2019 to June 2021 were analyzed retrospectively, including 168 patients with preoperative NHT and 217 patients with simple surgery. Clinical characteristics were compared in the above two groups, the laparoscopic RP (LRP) cohort (n = 234) and the robot-assisted laparoscopic radical prostatectomy (RALP) cohort (n = 151), respectively. Results: In the overall cohort, compared with the control group, the NHT group had a shorter operative time, less blood loss, a lower positive surgical margin rate, and a higher proportion of Gleason score (GS) downgrading after the operation (p < 0.05). However, there was no significant difference in hospitalization time, biochemical recurrence, urine leakage, urinary continence, or prostate-specific antigen (PSA) progression-free survival (p > 0.05). In the LRP cohort, it was found that the NHT group also had shorter operative time, less blood loss, lower positive surgical margin rate, a higher proportion of GS downgrading after the operation, and faster recovery of urinary control than the control group (p < 0.05). There was no marked difference in hospitalization time, biochemical recurrence, urinary leakage, or PSA progression-free survival. However, in the RALP cohort, the NHT group had a significant difference in the GS downgrading after the operation compared with the control group (p < 0.05). In the overall cohort, multiple analyses showed that initial PSA level, GS at biopsy, clinical T stage, lymph node invasion, use of NHT, and surgical methods were significantly associated with positive surgical margin (p < 0.05) while NHT did not account for biochemical recurrence (p > 0.05). Conclusions: NHT can lower the difficulty of surgery, reduce positive surgical margin rate, and help recovery in short-term urinary control in patients with high-risk prostate cancer after LRP. However, we do not have evidence on the benefit of NHT in high-risk PCa patients treated with RALP. For these patients, surgery can be performed as early as possible. Full article

This study aimed to examine the physical and mental Quality of Life (QoL) trajectories in prostate cancer (PCa) patients participating in the Pros-IT CNR study. QoL was assessed using the Physical (PCS) and Mental Component Score (MCS) of Short-Form Health Survey upon diagnosis and two years later. Growth mixture models were applied on 1158 patients and 3 trajectories over time were identified for MCS: 75% of patients had constantly high scores, 13% had permanently low scores and 12% starting with low scores had a recovery; the predictors that differentiated the trajectories were age, comorbidities, a family history of PCa, and the bowel, urinary and sexual functional scores at diagnosis. In the physical domain, 2 trajectories were defined: 85% of patients had constantly high scores, while 15% started with low scores and had a further slight decrease. Two years after diagnosis, the psychological and physical status was moderately compromised in more than 10% of PCa patients. For mental health, the trajectory analysis suggested that following the compromised patients at diagnosis until treatment could allow identification of those more vulnerable, for which a level 2 intervention with support from a non-oncology team supervised by a clinical psychologist could be of help. Full article