Robert L Grubb’s research while affiliated with Medical University of South Carolina and other places

Introduction: We report the first scoping review of the clinical urologic literature for photodynamic therapy (PDT) among multiple urologic malignancies. Materials and methods: A scoping review using Medline and Embase was performed for treatment of urologic malignancies with PDT. Results: There were 84 papers included with the majority involving bladder and prostate cancer. Upper tract urothelial cancer (UTUC) only comprised three publications and there was no clinical data for renal or testicular cancer. Utilizing PDT in prostate cancer led to a negative biopsy rate of 30%-100%. Bladder cancer treatment with PDT had a 3-month complete response rate of 31.5%-100%. UTUC management with PDT reported at least 50% complete response rate. Conclusions: Ultimately, PDT has been established as a safe and effective treatment for urologic malignancies and we provide the first comprehensive review of the literature regarding the utility of this treatment modality.

Bronchoperitoneal (BP) fistulas are exceedingly rare and complicated conditions. Given the rarity of this diagnosis, with reports limited to case reports or case series, there is limited literature regarding treatment, which ranges from conservative to surgical management. A search for 'bronchoperitoneal fistula from bladder cancer' on PubMed and Google Scholar revealed no reported studies. Therefore, to our knowledge, this is the first case of BP fistula caused by metastatic bladder cancer. Moreover, to our knowledge, we present the second instance in the literature of utilizing an endobronchial valve to treat a BP fistula. Ultimately, the procedure was successful and allowed for improved quality of life.

Testicular mesothelioma lacks the characteristic presentation of testicular malignancy and often has normal biomarkers at the time of diagnosis causing this malignancy to be overlooked and diagnosed intraoperatively during elective scrotal surgery. We present two cases of testicular mesothelioma that were diagnosed incidentally during hydrocelectomy. These cases emphasize the importance of considering testicular mesothelioma during hydrocele and scrotal mass workup and demonstrate the need for standardized guidelines for the management of testicular mesothelioma.

Dermatofibrosarcoma protuberans (DFSP) is a rare spindle cell soft tissue sarcoma of the dermis and subcutaneous tissue. We present the fourth case of scrotal DFSP in the literature, identified in a 32-year-old male with schizophrenia. Wide surgical excision and radical orchiectomy were performed revealing an uninvolved testicle and DFSP of the scrotum. A unique challenge to this case was concurrent aortic dissection and schizophrenia. Social determinants of health are associated with delay in presentation and poor appointment compliance in patients with schizophrenia. Ultimately, DFSP of the scrotum is an extremely rare condition with this presentation being only the fourth report in the literature. It is important to document these unique cases to establish differential diagnoses and optimize management.

Primitive neuroectodermal tumors (PNET) are rare, small round cell tumors that are difficult to diagnose. It is important to identify PNET early, utilizing immunohistochemistry and genetic markers, as it is often an aggressive cancer. PNET is most commonly described in men between the ages of 20 and 40, with very few case reports highlighting the development in pregnant patients. We present a case of localized renal PNET in a pregnant patient and highlight the diagnostic work-up and treatment as well as the relationship between pregnancy and the potential development of aggressive tumors.

TPS277 Background: Despite a growing number of treatment options for first-line mCRPC, approximately 40% of patients (pts) have radiographic progression within the first year. Co-inhibition of androgen receptor (AR) and PARP is a promising therapeutic strategy that leverages synthetic lethality induced by impaired double-strand DNA repair. Two phase III studies have shown improvement in radiographic progression-free survival (rPFS) in HRR-mutant pts with abiraterone + PARPi combinations vs abiraterone alone. However, the results in HRR-wild type pts are conflicting, with only one of the studies demonstrating a benefit with the abiraterone + PARPi combination. ENZ + RUCA has shown an acceptable safety profile & no significant drug-drug interactions (S-DDI) in a phase 1b trial. This allows its evaluation in mCRPC. Methods: CASPAR (A031902) is a phase 3 study in which 984 pts will be randomized on a 1:1 basis to ENZ plus RUCA/PBO. HRR gene aberration is not required for enrollment. All pts will undergo next-generation targeted exome sequencing from archival tumor tissue (new biopsy only required if no archival tissue is available). Treatment will be continued until disease progression and crossover is not allowed. Key eligibility criteria are age ≥ 18 years, ECOG PS 0-2, biopsy-proven prostate adenocarcinoma, progressive (PSA or radiographic) disease per Prostate Cancer Working Group 3 guidelines, measurable or non-measurable disease per RECIST 1.1, no prior treatment for mCRPC (prior docetaxel, abiraterone, darolutamide, or apalutamide in non-mCRPC setting is allowed), no significant uncontrolled comorbidity, and no medications with S-DDI with ENZ/RUCA. Hierarchical co-primary endpoints are overall survival (OS) and rPFS. The OS analysis will be undertaken as a primary endpoint if the rPFS endpoint is met. For a one-sided logrank test with a type 1 error rate equal to 0.025, the study has 90% power to detect a hazard ratio (HR) of 0.71 in rPFS (median rPFS of 15 and 21 months in control and combination arms, respectively), and 80% power to detect an HR of 0.80 in OS (median OS of 32 and 40 months, respectively). Key secondary endpoints are rPFS and OS in pts with vs without pathogenic BRCA1, BRCA2, or PALB2 alterations; and differences in adverse events and quality of life (QOL) outcomes between the treatment arms. QOL assessments include Functional Assessment of Cancer Therapy–Prostate (FACT-P), Brief Pain Inventory Short Form (BPI-SF), and EQ-5D-5L. A key correlative endpoint is the sensitivity of ctDNA testing for HRR gene alterations. Enrollment began in July 2021 & the study is available for participation to all US-NCTN sites. Clinical trial information: NCT04455750 .

Objective: To prospectively examine the influence of weight status on urinary and sexual function in clinically localized prostate cancer patients treated by radical prostatectomy (RP). Methods: The Prostatectomy, Incontinence and Erectile dysfunction study recruited patients at two US institutions between 2011-2014. At baseline, height and weight were measured, and urinary and sexual function were collected by the modified Expanded Prostate Cancer Index Composite-50. This index was repeated at the 5-week, 6-month, and 12-month post-surgical assessments and compared to baseline using linear generalized estimating equations. Logistic equations were used to evaluate the likelihood of functional recovery at the 6- and 12-month assessments. Result: Pre-surgery, nonobese patients (68.8% of 407 patients) had similar urinary function as those with obesity (p=0.217), but better sexual function (p=0.006). One year after surgery, 50.5% and 28.9% patients had recovered to baseline levels for urinary and sexual function, respectively. Recovery was not, however, uniform by obesity. Compared to those with obesity, nonobese patients had better urinary function at the 6- (p<0.001) and 12-month post-surgical assessments (p=0.011) and were more likely to recover their function by the 6-month assessment (OR=2.55, 95% CI=1.36-4.76). For sexual function, nonobese patients had better function at the 6- (p=0.028) and 12-month (p=0.051) assessments, but a similar likelihood of recovery one-year post-surgery. Conclusion: Nonobese prostate cancer patients had better and likely earlier recovery in urinary function post-surgery, and better sexual function both pre-and post-surgery. These findings support the potential for tailored pre-surgical counseling about RP side-effects and prehabilitation to improve these side-effects.

TPS5107 Background: Despite a growing number of treatment options for first line mCRPC, approximately 40% of patients (pts) have radiographic progression within the first year. Androgen receptor (AR) signaling inhibition increases genomic instability with double-strand DNA breaks & co-inhibition of AR & PARP induces synthetic lethality in multiple preclinical models. Homologous recombination repair (HRR) gene aberrations do not appear to be necessary for this synergy as demonstrated in a ph 3 clinical trial of abiraterone & olaparib where this combination improved radiographic progression-free survival (rPFS) in HRR-wild-type pts compared with abiraterone alone. A ph 1b trial has since shown that enzalutamide plus rucaparib has acceptable safety profile & no significant drug-drug interactions (S-DDI). Methods: CASPAR/A031902 (NCT04455750) is a ph 3 study in which 984 pts will be randomized 1:1 to enzalutamide plus rucaparib or placebo. HRR gene aberration is not required for enrollment. All pts will undergo next-generation targeted-exome sequencing from archival tumor tissue (new biopsy only required if no archival tissue available). Treatment will be continued until disease progression & crossover is not allowed. Key eligibility criteria are age ≥ 18 years, ECOG PS 0-2, biopsy-proven prostate adenocarcinoma, progressive (PSA or radiographic) disease per Prostate Cancer Working Group 3 guidelines, measurable or nonmeasurable disease per RECIST 1.1, no prior treatment for mCRPC (prior docetaxel, abiraterone, darolutamide, or apalutamide in non-mCRPC setting is allowed), no significant uncontrolled comorbidity, & no medications with S-DDI with enzalutamide/rucaparib. Hierarchical co-primary endpoints are rPFS & overall survival (OS). The OS analysis will be undertaken as a primary endpoint if the rPFS endpoint is met. For a one-sided logrank test with a type 1 error rate equal to 0.025, the study has 90% power to detect a hazard ratio (HR) of 0.71 in rPFS (median rPFS of 15 & 21 months in control & combination arms, respectively) & 80% power to detect an HR of 0.80 in OS (median OS of 32 & 40 months, respectively). Key secondary endpoints are rPFS & OS in pts with vs without pathogenic BRCA1, BRCA2, or PALB2 alterations; & differences in adverse events & quality of life (QOL) outcomes between the treatment arms. QOL assessments include Functional Assessment of Cancer Therapy–Prostate (FACT-P), Brief Pain Inventory Short Form (BPI-SF) & EQ-5D-5L. A key correlative endpoint is the sensitivity of ctDNA-based testing for alterations in HRR genes. Enrollment to CASPAR began in July 2021 & the study is available for participation to all US-NCTN sites with a projected enrollment of 3 years. Support: U10CA180821, U10CA180882, U24CA196171; U10CA180888. Clinical trial information: NCT04455750.

TPS194 Background: Despite a growing number of treatment options for first line mCRPC, approximately 40% of patients (pts) have radiographic progression within the first year. Androgen receptor (AR) signaling inhibition increases genomic instability with double-strand DNA breaks & co-inhibition of AR & PARP induces synthetic lethality in multiple preclinical models. Homologous recombination repair (HRR) gene aberrations do not appear to be necessary for this synergy as demonstrated in a ph 2 clinical trial of abiraterone & olaparib where this combination improved radiographic progression-free survival (rPFS) in HRR-wild-type pts compared with abiraterone alone. A ph 1b trial has since shown that enzalutamide plus rucaparib has acceptable safety profile & no significant drug-drug interactions (S-DDI). Methods: CASPAR/A031902 (NCT04455750) is a ph 3 study in which 984 pts will be randomized 1:1 to enzalutamide plus rucaparib or placebo. HRR gene aberration is not required for enrollment. All pts will undergo next-generation targeted-exome sequencing from archival tumor tissue (new biopsy only required if no archival tissue available). Treatment will be continued until disease progression & crossover is not allowed. Key eligibility criteria are age ≥ 18 years, ECOG PS 0-2, biopsy-proven prostate adenocarcinoma, progressive (PSA or radiographic) disease per Prostate Cancer Working Group 3 guidelines, measurable or nonmeasurable disease per RECIST 1.1, no prior treatment for mCRPC (prior docetaxel, abiraterone, darolutamide, or apalutamide in non-mCRPC setting is allowed), no significant uncontrolled comorbidity, & no medications with S-DDI with enzalutamide/rucaparib. Hierarchical co-primary endpoints are rPFS & overall survival (OS). The OS analysis will be undertaken as a primary endpoint if the rPFS endpoint is met. For a one-sided logrank test with a type 1 error rate equal to 0.025, the study has 90% power to detect a hazard ratio (HR) of 0.71 in rPFS (median rPFS of 15 & 21 months in control & combination arms, respectively) & 80% power to detect an HR of 0.80 in OS (median OS of 32 & 40 months, respectively). Key secondary endpoints are rPFS & OS in pts with vs without pathogenic BRCA1, BRCA2, or PALB2 alterations; & differences in adverse events & quality of life (QOL) outcomes between the treatment arms. QOL assessments include Functional Assessment of Cancer Therapy–Prostate (FACT-P), Brief Pain Inventory Short Form (BPI-SF) & EQ-5D-5L. A key correlative endpoint is the sensitivity of ctDNA-based testing for alterations in HRR genes. Enrollment to CASPAR began in July 2021 & the study is available for participation to all US-NCTN sites with a projected enrollment of 3 years. Support: U10CA180821, U10CA180882, U24CA196171; U10CA180888; Clovis Oncology; http://acknowledgments.alliancefound.org Clinical trial information: NCT04455750.